Saturday, November 30, 2013
Canada: Medical marijuana use without safety proof worries doctors
Canada
Medical marijuana use without safety proof worries doctors
Doctors being asked to prescribe cannabis without rigorous testing, CMA says
CBC News Posted: Nov 29, 2013 1:18 PM ET
Last Updated: Nov 29, 2013 10:28 PM ET
The Canadian Medical Association is worried that as large medical marijuana grow facilities get federal licences, more patients will be clamouring for a drug many doctors are uncomfortable prescribing..
http://www.cbc.ca/news/health/medical-marijuana-use-without-safety-proof-worries-doctors-1.2445249?cmp=rss
When the living and the deceased don't agree on organ donation
November 26, 2013
All 50 states and the District of Columbia have adopted the 2006 Revised Uniform Anatomical Gift Act (UAGA) or enacted similar legislation giving individuals the "First Person Authorization" (FPA) to consent to organ donation after death via a signed donor card or driver's license, or by enrollment in a donor registry. While such laws give hospitals legal authority to proceed with organ procurement without consent of the registered donor's family, a new study shows that organ procurement organizations' implementation of FPA has been inconsistent and incomplete.
"Sometimes what we preach and what we practice may not be the same thing, especially when dealing with very sensitive issues such as organ donation," said W. James Chon, MD, assistant professor of medicine at the University of Chicago Medicine, primary author of the study, which was published early online in the American Journal of Transplantation.
Chon and his colleagues conducted a web-based survey of the executive directors of 58 organ procurement organizations to assess their policies and practices regarding donations from registered donors in cases of family objections. Most of the respondents estimated the frequency of family objection as less than 10 percent.
Half the groups surveyed did not have a written policy for handling such scenarios. Twenty-one percent said they would first inform the family of the donor's wishes and proceed with procurement, and another 59 percent said they would proceed even if they could not persuade family members. Twenty percent, however, said they would not proceed with organ procurement unless they had consent of the family, and 35 percent had not procured organs against family objections in the past five years.
Chon said that despite the legal backing given by FPA legislation, procurement organizations still have difficulty dealing with family objections because questions about organ donation come at such an emotional time.
"When a deadly accident hits, the family is in a state of shock," he said. "Then out of nowhere, a total stranger comes up to say their son or daughter wanted to be an organ donor and the family often find it difficult to process the information in this time of emotional upheaval."
Lainie Friedman Ross, MD, PhD, the study's senior author and the Carolyn and Matthew Bucksbaum Professor of Clinical Ethics at the University of Chicago Medicine, said the work highlights the importance of people talking to family members about their organ donation wishes in the event of an untimely death.
"What this study shows is that family objections to a kin's decision is rare. However, we have to remember that it only addresses those cases in which an individual has made known his or her wishes about donation," she said. "Unfortunately, this is a minority of the country, so it is critical that we convince the public to express their wishes using web-based consent registries, organ donor cards, or driver's licenses."
Chon added that while organ procurement organizations should continue their efforts to enforce FPA in the face of family objections, increased public awareness about the critical need for donated organs will also help to limit the number of times families refuse to honor the wishes of a loved one.
"As people are better informed and better educated about why we're doing this, I think most people will agree that it's really up to the deceased person to dictate how the organs are used," he said.
The study, "A Survey of U.S. OPOs on Implementation of First Person Authorization," was published on Nov. 25, 2013 in the American Journal of Transplantation. Additional authors include Michelle Josephson, Yolanda Becker, Piotr Witkowski, Divya Arwindekar, Abhijit Naik, J. Richard Thistlethwaite, Jr. and Chuanhong Liao from the University of Chicago, and Elisa Gordon from Northwestern University.
UCH_036912 (2)
http://www.uchospitals.edu/news/2013/20131126-organ-donation.html
The University of Chicago Medicine
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FDA Approved Simeprevir: Welcomed, but not the proverbial “home-run”
by Dr. Joe Galati on 11/29/2013
This past week, the FDA gave approval to Janssen’s new drug to treat hepatitis C. Simeprevir, commercially know as OLYSIO, is the first new hepatitis C drug since the release of telapravir (Incevik) and boceprevir (Victrelis) in 2011. Simeprevir is a NS3/4A protease inhibitor, used in combination with interferon and ribavirin.
The release of simeprevir marks the beginning of a new wave of direct acting antiviral agents against the hepatitis C virus. Additional drugs are set for FDA approval, including the Gilead drug sofosbuvir in early December 2013.
Most of the new hepatitis C drugs will have a number of features in common.
These include:
Very high cure rate, in the 80-90% range – lower in null and non-responders
Less side effects
Shorter duration of treatment
Less pills to take each day
Cirrhosis reduces response rates
Less drug-drug interactions
Genotype 1 subtype differences exist
Looking at the dosing of simeprevir, I have attached the official product insert that describes how the drug will be doses. Several points to consider:
This is an interferon/ribavirin based therapy
Patients with genotype 1 need additional screening for the NS3 Q80K polymorphism
Those with this variant have a decreased response rate to the therapy, and should be considered for an alternative therapy
The initial dosing is 12 weeks of simeprevir with interferon and ribavirin, followed by an additional 12 or 36 weeks of interferon and ribavirin combination therapy.
There are drug-drug interaction which have to be monitored closely
FDA approval is for genotype 1 patients only
While the release of simeprevir is welcomed, it has not provided the proverbial “home-run” we have been looking for in our quest to cure hepatitis C. In well selected patients, achieving a better than 80% cure rate is available. The concerns I have relate to the Q80K polymorphism noted above. This will be an additional step required in screening our patients. Additionally, in patients with prior non-response or null responders, as well as those with cirrhosis, these patients will still require a full 48 week of interferon and ribavirin. One of the goals of the next generation of hepatitis C therapies is reduced interferon exposure, or complete elimination. Simeprevir does not fully meet this goal.
In the days to come, I will post additional information on sofosbuvir. For now, these are the highlights to consider (refer to this FDA document for additional details):
Sofosbuvir will likely receive FDA approval for Genotype 1,2,3, and 4 patients with hepatitis C
Interferon-free treatment in genotype 2 and 3 for 12 weeks
Sofosbuvir combined with interferon and ribavirin in genotype 1 and 4 for 12 to 16 weeks
This treatment strategy is far different than the simeprevir treatment noted above.
Looking further, we will eventually have all interferon-free protocols. It is anticipated that as additional new drugs are approved, they will be combined (example sofosbuvir and simeprevir), allowing us to treat a wide range of patients, safely, and with a cure rate many of us may have never envisioned 20 years ago.
For a consultation to see if you are a candidate for these new drugs, contact Lexa at our office at 713-794-0700 and visit our webpage for additional information.
Source - http://blog.texasliver.com/#sthash.ju2JBHrL.dpuf
Related:
OLYSIO™ (simeprevir) Receives FDA Approval for Combination Treatment of Chronic Hepatitis C
HCV Drug Olysio (simeprevir) - The New Kid On The Block
OLYSIO Website
Prescribing Information
Patient Information
Important Safety Information
Simeprevir and Sofosbuvir-The Next Wave of Hepatitis C Treatment
Friday, November 29, 2013
Lucinda Porter: The Hepatitis C Battle Won - The War Continues
I'm not a name dropper, but let me drop this, my friend Lucinda Porter had a small cameo appearance on Hep C TV. I know!
Right off folks I noticed something different, lovely Lucinda looked healthy, vibrant, young, even Gwyneth Paltrow like, she looked new.
I knew Lucinda had participated in a HCV trial using sofosbuvir for twelve weeks, but I had no idea it was working so well. Why else would Lucinda look so hot? It must be the drugs.
Gossip And L.
I never spread gossip, however, I heard L. exhibited some moody behavior during HCV therapy.
I refuse to believe it, and would never make anyone's irrational behavior under the influence of lifesaving agents public knowledge. So you didn't hear that from me.
Checking On Lucinda
I frequently stroll over to Gwyneths blog hoping to find the results from her 24 week post PCR. The test is given 24 weeks after finishing HCV treatment and will determine if the virus is gone for good, or nondetectable.
Drum Roll Please..............
Lucinda Made An Announcement - And I Missed It
I get to announce my 24-week post-treatment follow-up results: hepatitis C is nondetectable
Congratulations Lucinda !!!!!!!!!!!!!!
The War Continues
A Word From Ms. Porter
I wish I was out of a job, but just because I am free of hepatitis C doesn’t mean that the world is. I feel like I have just begun. Now I have high-powered hope on my side and I want to spread this hope to all those who need it.
The HCV Drugs: Sofosbuvir, Ledipasvir Alone Or With Ribavirin
Lucinda treated for 12 weeks using sofosbuvir, ledipasvir, and ribavirin.
In the November issue of "The Lancet" researchers suggest that the fixed-dose combination of sofosbuvir-ledipasvir alone or with ribavirin has the potential to cure most patients with genotype-1 HCV including those with compensated cirrhosis or who have previously failed treatment with protease inhibitors.
Accomplished AuthorLucinda is an accomplished author, with two books on hepatitis C, the latest "Hepatitis C Treatment One Step at a Time" is a great book to sleep with - keep it close during treatment.
A Proficient Public Speaker
If you are a fan, like myself, you'll enjoy watching our advocate speak passionately about HCV, here.
Find Pretty Porter On The Web
Follow L on Twitter, connect on Facebook and read her blogs Lucinda Porter, RN and The Hepatitis Comics: Levity for the Liver.
On A Personal Note.....
When I first heard of "The Porter" it was some fifteen years ago, I was starting treatment looking for information. I found that information and more at the "Peoples Hepatitis C Website" which remains my trusted source for all things HCV.
Flash Forward From 1999 To 2013
Today, I am still virus free, living life, and celebrating each day as I watch my family grow and prosper. As I type this, especially after just spending 48 hours with my family, and playing with the short people, Nana's computer screen has become blurry, my eyes have quickly filled with tears. From the bottom of my heart, thank you Lucinda Porter, Alan Franciscus, C.D. Mazoff, PhD and the staff at HCV Advocate for helping me find my cure, I am truly full of gratitude, thank you.
See you all soon
Tina
Tuesday, November 26, 2013
Good Gravy: HCV, Fatty Liver, And Thanksgiving
My timing, like my cooking, is terrible, no one wants to eat my turkey or read about fatty liver disease two days before Thanksgiving.
Maybe if I ease into the good, the bad, and the ugly, you may forgive me.
Fun Fat Fact
This year the average American will consume 4,500 calories and 229 grams of fat on Thanksgiving day, according to the Calorie Control Council.
Oh, you heard that fun fact. Yeah, me too.
The Shame
I tried to deliberately sneak in the popular tagline "The average American will consume 4,500 calories and 229 grams of fat on Thanksgiving day" into an otherwise almost profound festive holiday article. Why? I read the tagline today, here and here, and last year at Time.com, the temptation became to great not to use it. I get excited.
Enter. Did You Know?
Did You Know?
Hepatitis C, Genotype 3 And Fatty Liver
Did you know that hepatitis C can directly cause fatty liver - particularly in HCV genotype 3? Steatosis (fatty liver) is extremely common in people with chronic hepatitis C, close to 40% of people with hepatitis C have steatosis, compared to about 14% to 31% of the general population. All genotypes can trigger the condition, but people with genotype 3 have a higher risk at 60% - 80% for developing moderate or severe steatosis. The full text article published April 2013 can be found, here.
Key Enzyme May Explain How Hepatitis C Infection Causes Fatty Liver
Did you know that in 2008 researchers from the University of Pittsburgh found a key enzyme highly elevated in human liver cells exposed to the hepatitis C virus? The enzyme is known to participate in fat production and may explain how hepatitis C infection causes fatty liver, the study was published in Hepatology.
Hepatitis C, Liver Cancer And Fatty Liver
Did you know that several clinical papers have repeatedly found an association between fatty liver and hepatocellular carcinoma development in people with chronic hepatitis C? Check out the data published online June 2007, in Cancer.
Happy Thanksgiving Mr. President
Did you know the president recently reported within the next 5 years fatty liver disease may surpass hepatitis C as the leading cause of liver transplantation? Not Obama, the other president - AASLD president, J. Gregory Fitz, MD.
AASLD coverage @ Healio
Once considered largely benign, fatty liver disease may overtake hepatitis C as the leading cause of liver transplant within 5 years, American Association for the Study of Liver Disease President J. Gregory Fitz, MD, said at The Liver Meeting opened here, particularly considering recent improvements in HCV therapies.
"Suddenly it’s realistic to think that we'll be able to cure most patients with hepatitis C" Fitz said, noting that almost simultaneously, however, fatty liver disease has moved from being considered “an incidental accompaniment of obesity or diabetes; now it’s crystal clear that this alone can go ahead and cause liver fibrosis and scarring and liver failure.”
Despite the rapid advances in HCV treatments which Fitz characterized as a "revolution,” he noted physicians still have an uphill battle ahead of them with the disease.Continue reading...
What Is Steatosis?
Steatosis is the build up of fat within the liver, also known as ‘fatty liver. The accumulated fat can trigger inflammation which may eventually lead to fibrosis, or scarring of the liver. As mentioned, research has shown the significance and relationship of steatosis to the hepatitis C virus (HCV).
Weight loss in overweight people with chronic HCV will help reduce inflammation, slow down disease progression (liver damage) and improve liver function. A 2013 study published in Nutrition found exercise, a low-fat or low-calorie diet in people with HCV improved fibrosis, steatosis and insulin resistance.
*A comprehensive collection of liver health articles can be found, here.
How Not to Gain Weight This Thanksgiving
Here are a few helpful suggestions;
1-Try to sit across from a skinny in-law, it works for me. But, not so much after she leaves.
2-Sit at the children's table, learn from them, they only eat half of what we crave.
3-Take a walk after dinner
4-Take a walk on Friday, after you sneak another piece of pie.
5-Take a walk on Saturday, after you eat another "microwave mini" meal, complete with good/bad gravy.
6- Take a walk on Sunday, after you finish all the leftovers.
7-Please consider eating foods low in fat - all year long.
5-Smile, love your liver, love life, do it for your family.
See you all after the holiday, stay healthy and safe.
Happy Thanksgiving
Effect of fibrosis on adverse events in patients with hepatitis C treated with telaprevir
Alimentary Pharmacology & Therapeutics
Early View (Online Version of Record published before inclusion in an issue)
Effect of fibrosis on adverse events in patients with hepatitis C treated with telaprevir
K. Bichoupan1,*, J. M. Schwartz2, V. Martel-Laferriere1, E. R. Giannattasio2, K. Marfo2, J. A. Odin1, L. U. Liu1, T. D. Schiano1, P. Perumalswami1, M. Bansal1, P. J. Gaglio2, H. Kalia2, D. T. Dieterich1, A. D. Branch1, J. F. Reinus2
Effect of fibrosis on adverse events in patients with hepatitis C treated with telaprevir
A study published ahead of print the Alimentary Pharmacology & Therapeutics investigates adverse events of telaprevir-based therapy in patients with and without advanced fibrosis or cirrhosis.
Summary Source
A study published ahead of print the Alimentary Pharmacology & Therapeutics investigates adverse events of telaprevir-based therapy in patients with and without advanced fibrosis or cirrhosis.
Data about adverse events are needed to optimise telaprevir-based therapy in a broad spectrum of patients.
Dr Bichoupan and colleagues from New York, USA investigated adverse events of telaprevir-based therapy in patients with and without advanced fibrosis or cirrhosis in a real-world setting.
Data on 174 hepatitis C-infected patients initiating telaprevir-based therapy at Mount Sinai and Montefiore medical centres were collected.
Biopsy data and FIB-4 scores identified patients with advanced fibrosis
The research team built multivariable fully adjusted models to assess the effect of advanced fibrosis on specific adverse events and discontinuation of treatment due to an adverse event.
The team reported that patients with and without advanced fibrosis were similar in BMI, ribavirin exposure, gender, prior treatment history, hemoglobin and creatinine, but differed in race.
Overall, 47% of patients completed treatment and 40% of patients achieved SVR.
Treated patients with and without advanced fibrosis or cirrhosis had similar rates of adverse events.
The team noted that advanced fibrosis was independently associated with ano-rectal discomfort.
The researchers found that 3 patients decompensated and had advanced fibrosis.
The discontinuation of all treatment medications due to an adverse event was significantly associated with older age, female gender, and lower platelets.
Dr Bichoupan's team concludes, "Adverse events were common, but were not significantly related to the presence of advanced fibrosis or cirrhosis."
"More critical monitoring in older and female patients with low platelets throughout treatment may reduce adverse event-related discontinuations
Aliment Pharmacol Ther 2013: 38(11-12): 1373–1384
26 November 2013
Alimentary Pharmacology & Therapeutics
Discussion Only
Full Text Available Here
Article first published online: 24 NOV 2013 DOI: 10.1111/apt.12560
We analysed the occurrence rates of adverse events and treatment discontinuation during TVR in patients with genotype-1 HCV infection, with special attention to individuals with advanced fibrosis or cirrhosis. In addition, we identified factors associated with treatment discontinuation due to adverse events and other factors that were associated with specific adverse events.
Most importantly, we found the presence of advanced fibrosis or cirrhosis to have no effect on the safety of TVR. Through a multivariable fully adjusted model, fibrosis stage had no effect on drug discontinuation due to adverse events. Older age, lower haemoglobin and lower BMI were all significantly associated with severe anaemia. Higher levels of haemoglobin also were associated with fatigue, hypokalemia and ano-rectal discomfort. This could be explained by the fact that patients with higher haemoglobin levels were likely to remain on treatment longer and were thus exposed to more drug. We were surprised by the association between previous treatment history and skin burning, but are aware that our sample size is small. Our most important finding regarding adverse events was the strong associations between black race and naïve or prior-relapse patients with hospital admissions.
Our results reflect the fact that experience in daily clinical practice (effectiveness) may be different from that in registration trials (efficacy).[13] The high rate of treatment discontinuation due to adverse events in members of our cohort was not surprising as randomised controlled trials recruit lower risk patients that are intensely monitored. In the ADVANCE[5] and REALIZE[6] trials, 73% and 62% of telaprevir-treated patients completed therapy, respectively. Our treatment completion rate of 47% highlights the effect that clinical-trial monitoring and patient selection may have on efficacy. In addition, adverse events caused 22% of our patients, but only 10–13% of trial participants, to discontinue therapy. In our study, prior treatment was not associated with discontinuation due to an adverse event. Other studies, notably CUPIC (cite here), have provided additional data regarding results of TVR in well-compensated cirrhotics.
Differences in the patient populations studied may help explain why our real-world treatment results differ from those of the registration trials. Our study included older patients, more patients with advanced fibrosis or cirrhosis, more black and Hispanic patients, and larger patients (BMI and weight) than did the registration trials. In addition, our inclusion and exclusion criteria were more flexible than those found in randomised controlled trials. As a result, our patients may have been less adherent and sicker than those in clinical trials.
The issue of the ageing HCV population is one that clinicians must increasingly address. In our patients, older age was significantly associated with treatment discontinuation of all drugs due to an adverse event. The mean patient ages in REALIZE[6] and ADVANCE[5] were 51 (Range: 23–69) and 49 years (Range: 19–69) respectively. The mean age of our patients was 56 years and the median age 58 years with a range of 26–74. We treated 17 patients (10%) over age 65 years; data on patients over age 65 years were lacking in the registration trials.[10] Recently, Hu et al.[14] reported poorer SVR rates and greater treatment withdrawal rates during 24 weeks of dual therapy in geriatric as compared with younger patients. Older patients in their study also were more likely to relapse. The effect of age on safety and SVR was investigated in two other studies, but no significant association was found, possibly because of small sample sizes.[15, 16] Our finding suggests that the influence of age on the effectiveness of future treatments be investigated.
Anaemia is the most difficult adverse event to control during triple therapy with a protease inhibitor-containing regimen. In our patients, severe anaemia was associated with older age, lower baseline haemoglobin and lower BMI. These same predictive factors also have been found by Butt et al. in HCV-HIV co-infected patients being treated with long-term pegylated interferon alfa-2a and ribavirin.[17] As pegylated interferon causes suppression of hematopoiesis and ribavirin causes haemolysis,[18-20] lower BMI may lead to greater ribavirin exposure resulting in more anaemia. Interestingly, we saw a strong relationship between EPO use and the completion of therapy, suggesting that improved prediction and management of anaemia may enhance treatment completion rates. Note must be made of the fact that ribavirin dose reductions could not be obtained for all patients in our study limiting the assessment of the effect of growth factors on response.
Telaprevir treatment is only indicated in patients with compensated (Child-Pugh class A) cirrhosis.[4] The overall number of patients with bridging fibrosis or cirrhosis in ADVANCE was only 21% of the entire cohort.[5] Our study provides more information about the effect of fibrosis stage on treatment-related side effects. With the exception of ano-rectal discomfort, we found no significant difference in the side-effect profile of TVR in patients with or without advanced liver fibrosis. We suspect that the difference in rates of ano-rectal discomfort was due to immune compromise in patients with advanced fibrosis.[21, 22] Our study provides more information about the effect of fibrosis stage on treatment-related side effects.
Our study also provides additional information on the relationship between race and treatment safety. Only 7% of patients in ADVANCE were black and only 10% were Hispanic. In the REALIZE study, 4% of patients were black and 9% were Hispanic in the nonlead-in telaprevir group. Twenty-two per cent of patients in our cohort were black and 32% were Hispanic. We did not find race to be predictive of treatment discontinuation due to an adverse event. This can be explained partially by the small effect of race and ethnicity on pharmacokinetic properties of ribavirin and pegylated interferon reported by Brennan et al.[23] Other work has shown that black patients treated with dual therapy have lower SVR rates than other individuals.[24-26]
Our study was limited by relatively small sample size, the use of medical records as a source of information and lack of biopsy data for all patients, which may have caused some patients in our cohort to be misclassified as having either F0–F2 or F3–F4 fibrosis. Collected data were based on standard clinical treatment. For this reason, ITPA genotype and IL28b data were lacking, preventing us from building meaningful SVR models. In addition, during the implementation of any new treatment regimen, there may be a learning curve with respect to patient selection and side-effect management. Our study was conducted in an academic medical setting where patients may be different from those in other private practice settings as well as in clinical trials. The house staff and physician extenders assessed adverse events at every visit and in phone conversations. Finally, it must be understood that we only observed associations between observed factors in our study group and outcomes. We do not construe these factors to be the sole cause of these adverse events and discontinuations.
Recently, Hezode et al. published a study examining the safety and efficacy of 16 weeks of telaprevir and boceprevir in well-compensated cirrhotics. In the CUPIC study by week 16, 23% discontinued all treatment medications and 15% discontinued due to adverse events.[27] In an updated analysis from the International Liver Congress Meeting in Amsterdam 2013, 47% of patients discontinued prematurely and 21% discontinued due to severe adverse events.[28] Our results support the results in the CUPIC trial. Our results are remarkably similar in that 52% discontinued treatment early and 22% discontinued due to adverse events. In addition, results from our multivariable analysis echo similar conclusions by Hezode et al. In both studies, low platelets were associated with discontinuation due to an adverse event, and older age and lower baseline haemoglobin were associated with anaemia.
In summary, our data show that there were few differences in the side-effect profile of triple therapy between patients with advanced fibrosis or cirrhosis and those without. Despite the lack of difference found between patients with and without advanced fibrosis or cirrhosis, the rate of adverse events was still high. Providers must be vigilant in monitoring for safety in all patients treated with telaprevir. Our findings may help practitioners increase the safety of HCV treatment by increasing awareness of potential risk factors for development of adverse events. Our study group represents the composition of the HCV-infected population as it may appear in the future.[29] Older and female patients with low platelet counts may experience more severe side effects of triple therapy, suggesting that closer monitoring of these patients may be prudent. We also observed four decompensation events in three patients with advanced fibrosis. Until new and safer drugs for treatment of genotype-1 hepatitis C become available for clinical use, more information about the effects of race and fibrosis stage on the tolerability and outcome of therapy is needed.
http://onlinelibrary.wiley.com/doi/10.1111/apt.12560/full
Early View (Online Version of Record published before inclusion in an issue)
Effect of fibrosis on adverse events in patients with hepatitis C treated with telaprevir
K. Bichoupan1,*, J. M. Schwartz2, V. Martel-Laferriere1, E. R. Giannattasio2, K. Marfo2, J. A. Odin1, L. U. Liu1, T. D. Schiano1, P. Perumalswami1, M. Bansal1, P. J. Gaglio2, H. Kalia2, D. T. Dieterich1, A. D. Branch1, J. F. Reinus2
Effect of fibrosis on adverse events in patients with hepatitis C treated with telaprevir
A study published ahead of print the Alimentary Pharmacology & Therapeutics investigates adverse events of telaprevir-based therapy in patients with and without advanced fibrosis or cirrhosis.
Summary Source
A study published ahead of print the Alimentary Pharmacology & Therapeutics investigates adverse events of telaprevir-based therapy in patients with and without advanced fibrosis or cirrhosis.
Data about adverse events are needed to optimise telaprevir-based therapy in a broad spectrum of patients.
Dr Bichoupan and colleagues from New York, USA investigated adverse events of telaprevir-based therapy in patients with and without advanced fibrosis or cirrhosis in a real-world setting.
Data on 174 hepatitis C-infected patients initiating telaprevir-based therapy at Mount Sinai and Montefiore medical centres were collected.
Biopsy data and FIB-4 scores identified patients with advanced fibrosis
The research team built multivariable fully adjusted models to assess the effect of advanced fibrosis on specific adverse events and discontinuation of treatment due to an adverse event.
The team reported that patients with and without advanced fibrosis were similar in BMI, ribavirin exposure, gender, prior treatment history, hemoglobin and creatinine, but differed in race.
Overall, 47% of patients completed treatment and 40% of patients achieved SVR.
Treated patients with and without advanced fibrosis or cirrhosis had similar rates of adverse events.
The team noted that advanced fibrosis was independently associated with ano-rectal discomfort.
The researchers found that 3 patients decompensated and had advanced fibrosis.
The discontinuation of all treatment medications due to an adverse event was significantly associated with older age, female gender, and lower platelets.
Dr Bichoupan's team concludes, "Adverse events were common, but were not significantly related to the presence of advanced fibrosis or cirrhosis."
"More critical monitoring in older and female patients with low platelets throughout treatment may reduce adverse event-related discontinuations
Aliment Pharmacol Ther 2013: 38(11-12): 1373–1384
26 November 2013
Alimentary Pharmacology & Therapeutics
Discussion Only
Full Text Available Here
Article first published online: 24 NOV 2013 DOI: 10.1111/apt.12560
We analysed the occurrence rates of adverse events and treatment discontinuation during TVR in patients with genotype-1 HCV infection, with special attention to individuals with advanced fibrosis or cirrhosis. In addition, we identified factors associated with treatment discontinuation due to adverse events and other factors that were associated with specific adverse events.
Most importantly, we found the presence of advanced fibrosis or cirrhosis to have no effect on the safety of TVR. Through a multivariable fully adjusted model, fibrosis stage had no effect on drug discontinuation due to adverse events. Older age, lower haemoglobin and lower BMI were all significantly associated with severe anaemia. Higher levels of haemoglobin also were associated with fatigue, hypokalemia and ano-rectal discomfort. This could be explained by the fact that patients with higher haemoglobin levels were likely to remain on treatment longer and were thus exposed to more drug. We were surprised by the association between previous treatment history and skin burning, but are aware that our sample size is small. Our most important finding regarding adverse events was the strong associations between black race and naïve or prior-relapse patients with hospital admissions.
Our results reflect the fact that experience in daily clinical practice (effectiveness) may be different from that in registration trials (efficacy).[13] The high rate of treatment discontinuation due to adverse events in members of our cohort was not surprising as randomised controlled trials recruit lower risk patients that are intensely monitored. In the ADVANCE[5] and REALIZE[6] trials, 73% and 62% of telaprevir-treated patients completed therapy, respectively. Our treatment completion rate of 47% highlights the effect that clinical-trial monitoring and patient selection may have on efficacy. In addition, adverse events caused 22% of our patients, but only 10–13% of trial participants, to discontinue therapy. In our study, prior treatment was not associated with discontinuation due to an adverse event. Other studies, notably CUPIC (cite here), have provided additional data regarding results of TVR in well-compensated cirrhotics.
Differences in the patient populations studied may help explain why our real-world treatment results differ from those of the registration trials. Our study included older patients, more patients with advanced fibrosis or cirrhosis, more black and Hispanic patients, and larger patients (BMI and weight) than did the registration trials. In addition, our inclusion and exclusion criteria were more flexible than those found in randomised controlled trials. As a result, our patients may have been less adherent and sicker than those in clinical trials.
The issue of the ageing HCV population is one that clinicians must increasingly address. In our patients, older age was significantly associated with treatment discontinuation of all drugs due to an adverse event. The mean patient ages in REALIZE[6] and ADVANCE[5] were 51 (Range: 23–69) and 49 years (Range: 19–69) respectively. The mean age of our patients was 56 years and the median age 58 years with a range of 26–74. We treated 17 patients (10%) over age 65 years; data on patients over age 65 years were lacking in the registration trials.[10] Recently, Hu et al.[14] reported poorer SVR rates and greater treatment withdrawal rates during 24 weeks of dual therapy in geriatric as compared with younger patients. Older patients in their study also were more likely to relapse. The effect of age on safety and SVR was investigated in two other studies, but no significant association was found, possibly because of small sample sizes.[15, 16] Our finding suggests that the influence of age on the effectiveness of future treatments be investigated.
Anaemia is the most difficult adverse event to control during triple therapy with a protease inhibitor-containing regimen. In our patients, severe anaemia was associated with older age, lower baseline haemoglobin and lower BMI. These same predictive factors also have been found by Butt et al. in HCV-HIV co-infected patients being treated with long-term pegylated interferon alfa-2a and ribavirin.[17] As pegylated interferon causes suppression of hematopoiesis and ribavirin causes haemolysis,[18-20] lower BMI may lead to greater ribavirin exposure resulting in more anaemia. Interestingly, we saw a strong relationship between EPO use and the completion of therapy, suggesting that improved prediction and management of anaemia may enhance treatment completion rates. Note must be made of the fact that ribavirin dose reductions could not be obtained for all patients in our study limiting the assessment of the effect of growth factors on response.
Telaprevir treatment is only indicated in patients with compensated (Child-Pugh class A) cirrhosis.[4] The overall number of patients with bridging fibrosis or cirrhosis in ADVANCE was only 21% of the entire cohort.[5] Our study provides more information about the effect of fibrosis stage on treatment-related side effects. With the exception of ano-rectal discomfort, we found no significant difference in the side-effect profile of TVR in patients with or without advanced liver fibrosis. We suspect that the difference in rates of ano-rectal discomfort was due to immune compromise in patients with advanced fibrosis.[21, 22] Our study provides more information about the effect of fibrosis stage on treatment-related side effects.
Our study also provides additional information on the relationship between race and treatment safety. Only 7% of patients in ADVANCE were black and only 10% were Hispanic. In the REALIZE study, 4% of patients were black and 9% were Hispanic in the nonlead-in telaprevir group. Twenty-two per cent of patients in our cohort were black and 32% were Hispanic. We did not find race to be predictive of treatment discontinuation due to an adverse event. This can be explained partially by the small effect of race and ethnicity on pharmacokinetic properties of ribavirin and pegylated interferon reported by Brennan et al.[23] Other work has shown that black patients treated with dual therapy have lower SVR rates than other individuals.[24-26]
Our study was limited by relatively small sample size, the use of medical records as a source of information and lack of biopsy data for all patients, which may have caused some patients in our cohort to be misclassified as having either F0–F2 or F3–F4 fibrosis. Collected data were based on standard clinical treatment. For this reason, ITPA genotype and IL28b data were lacking, preventing us from building meaningful SVR models. In addition, during the implementation of any new treatment regimen, there may be a learning curve with respect to patient selection and side-effect management. Our study was conducted in an academic medical setting where patients may be different from those in other private practice settings as well as in clinical trials. The house staff and physician extenders assessed adverse events at every visit and in phone conversations. Finally, it must be understood that we only observed associations between observed factors in our study group and outcomes. We do not construe these factors to be the sole cause of these adverse events and discontinuations.
Recently, Hezode et al. published a study examining the safety and efficacy of 16 weeks of telaprevir and boceprevir in well-compensated cirrhotics. In the CUPIC study by week 16, 23% discontinued all treatment medications and 15% discontinued due to adverse events.[27] In an updated analysis from the International Liver Congress Meeting in Amsterdam 2013, 47% of patients discontinued prematurely and 21% discontinued due to severe adverse events.[28] Our results support the results in the CUPIC trial. Our results are remarkably similar in that 52% discontinued treatment early and 22% discontinued due to adverse events. In addition, results from our multivariable analysis echo similar conclusions by Hezode et al. In both studies, low platelets were associated with discontinuation due to an adverse event, and older age and lower baseline haemoglobin were associated with anaemia.
In summary, our data show that there were few differences in the side-effect profile of triple therapy between patients with advanced fibrosis or cirrhosis and those without. Despite the lack of difference found between patients with and without advanced fibrosis or cirrhosis, the rate of adverse events was still high. Providers must be vigilant in monitoring for safety in all patients treated with telaprevir. Our findings may help practitioners increase the safety of HCV treatment by increasing awareness of potential risk factors for development of adverse events. Our study group represents the composition of the HCV-infected population as it may appear in the future.[29] Older and female patients with low platelet counts may experience more severe side effects of triple therapy, suggesting that closer monitoring of these patients may be prudent. We also observed four decompensation events in three patients with advanced fibrosis. Until new and safer drugs for treatment of genotype-1 hepatitis C become available for clinical use, more information about the effects of race and fibrosis stage on the tolerability and outcome of therapy is needed.
http://onlinelibrary.wiley.com/doi/10.1111/apt.12560/full
Hepatitis C: Boehringer Ingelheim's faldaprevir granted accelerated assessment from European Medicines Agency
Hepatitis C: Boehringer Ingelheim's faldaprevir granted accelerated assessment from European Medicines Agency
- Accelerated assessment reserved for medicinal products of major interest from the viewpoint of public health and therapeutic innovation1
- Submission based on comprehensive development programme including the Phase III STARTVerso™ data aiming to demonstrate the efficacy and safety of faldaprevir* + PegIFN/RBV in a broad range of genotype-1 infected hepatitis C patients2,3,4
November 26, 2013 02:00 AM Eastern Standard Time
INGELHEIM, Germany--(BUSINESS WIRE)
The application for European marketing authorisation of faldaprevir*, a potent second generation oral protease inhibitor, has been fully validated and granted accelerated assessment by the European Medicines Agency (EMA).5,6 Boehringer Ingelheim is seeking marketing approval of faldaprevir* in combination with pegylated interferon and ribavirin (PegIFN/RBV) for the treatment of a broad range of patients with genotype-1 (GT-1) hepatitis C, including difficult-to-cure populations such as those with HIV co-infection or advanced liver disease.
“Faldaprevir* has been studied with pegylated interferon and ribavirin in a broad range of more than 3,300 patients typical of those that doctors see in every day clinical practice. Faldaprevir* has demonstrated strong efficacy and a robust safety profile while also offering the convenience of once-daily dosing and no food restrictions,” said Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim. “The acceptance for accelerated assessment by the EMA supports our position that if approved, faldaprevir* will provide an important alternative to currently available hepatitis C treatments.”
Accelerated assessment status does not automatically lead to a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) or the granting of a marketing authorization by the European Commission.1 If approved by the European Commission, faldaprevir* could be available for marketing in the EU in the second half of 2014.
The EMA Marketing Authorisation Application is based on a comprehensive clinical development programme for faldaprevir* with a particular focus on the Phase III STARTVerso™ trial data, recently presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). These studies include data for faldaprevir* in:
Faldaprevir* is the foundation of Boehringer Ingelheim’s hepatitis C treatment pipeline and is being developed in combinations both with and without interferon. In addition to the interferon-based faldaprevir* regimen that has been submitted for marketing approval, Boehringer Ingelheim aims to deliver one of the first interferon-free regimens for the treatment of hepatitis C infection. The goal is to make an interferon-free future a reality for a broad range of hepatitis C patients. Pivotal Phase III HCVerso® data for the interferon-free regimen of faldaprevir*, deleobuvir* and ribavirin will be available in 2014.
* Faldaprevir and deleobuvir are investigational compounds and not yet approved. Their safety and efficacy have not yet been fully established.
“The acceptance for accelerated assessment by the EMA supports our position that if approved, faldaprevir* will provide an important alternative to currently available hepatitis C treatments.”
The application for European marketing authorisation of faldaprevir*, a potent second generation oral protease inhibitor, has been fully validated and granted accelerated assessment by the European Medicines Agency (EMA).5,6 Boehringer Ingelheim is seeking marketing approval of faldaprevir* in combination with pegylated interferon and ribavirin (PegIFN/RBV) for the treatment of a broad range of patients with genotype-1 (GT-1) hepatitis C, including difficult-to-cure populations such as those with HIV co-infection or advanced liver disease.
“Faldaprevir* has been studied with pegylated interferon and ribavirin in a broad range of more than 3,300 patients typical of those that doctors see in every day clinical practice. Faldaprevir* has demonstrated strong efficacy and a robust safety profile while also offering the convenience of once-daily dosing and no food restrictions,” said Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim. “The acceptance for accelerated assessment by the EMA supports our position that if approved, faldaprevir* will provide an important alternative to currently available hepatitis C treatments.”
Accelerated assessment status does not automatically lead to a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) or the granting of a marketing authorization by the European Commission.1 If approved by the European Commission, faldaprevir* could be available for marketing in the EU in the second half of 2014.
The EMA Marketing Authorisation Application is based on a comprehensive clinical development programme for faldaprevir* with a particular focus on the Phase III STARTVerso™ trial data, recently presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). These studies include data for faldaprevir* in:
- Treatment naïve patients with the majority having benefited from shorter treatment duration and achieved viral cure2
- Difficult-to-cure patient populations such as those with HIV co-infection4 or advanced liver disease2,3
- Patients with the Q80K polymorphism (this mutation is considered to affect the efficacy of other second generation protease inhibitors)2
- Treatment experienced patients who have relapsed, partially responded or failed to respond to previous therapy3
Faldaprevir* is the foundation of Boehringer Ingelheim’s hepatitis C treatment pipeline and is being developed in combinations both with and without interferon. In addition to the interferon-based faldaprevir* regimen that has been submitted for marketing approval, Boehringer Ingelheim aims to deliver one of the first interferon-free regimens for the treatment of hepatitis C infection. The goal is to make an interferon-free future a reality for a broad range of hepatitis C patients. Pivotal Phase III HCVerso® data for the interferon-free regimen of faldaprevir*, deleobuvir* and ribavirin will be available in 2014.
* Faldaprevir and deleobuvir are investigational compounds and not yet approved. Their safety and efficacy have not yet been fully established.
Monday, November 25, 2013
J&J HCV drug OK'd; educational push planned
J&J HCV drug OK'd; educational push planned
Janssen's hepatitis C drug Olysio (simeprevir) scored FDA approval Friday evening, kicking off a new wave of hepatitis C drugs. It offers modest benefit over standard of care, but a subgroup of patients has encountered resistance, and the med could have trouble catching on as newer antivirals become more broadly available for treating the liver-destroying disease.
An NS3/4A protease inhibitor, Olysio was approved as part of a treatment regimen that also includes pegylated interferon (INF) and ribavirin (RBV) in patients with genotype-1 infection, which accounts for most cases of the virus. It followed a unanimous vote from an FDA ad-com panel in October for that same genotype.
Janssen has priced Olysio at a wholesale acquisition price of $22,120 per bottle of 28 capsules (150 mg capsules), which is an approximately one-month supply. "We believe that the price of Olysio reflects its value and demonstrated efficacy and safety profile," said Janssen spokesman Craig Stoltz via e-mail, adding that Janssen is offering a support program including help with access.
That's roughly $66,360 for a three-month course. Pooled analysis of two Phase III trials demonstrated that 80% of treatment-naïve patients taking Olysio were able to clear the virus at 12 weeks (SVR12), vs. 50% of patients in placebo groups.
Efficacy wise, the drug offers a slight benefit over the two currently used direct-acting antivirals, Vertex's Incivek and Merck's Victrelis (both of which were approved in 2011), with similar to better safety/tolerability, according to an October analyst note from inThought Research.
But the efficacy of Olysio, in combination with INF and RBV, is greatly decreased in patients who have genotype 1a Q80K, a naturally occurring variation in the HCV NS3/4A protease enzyme that was identified in 48% of patients with GT-1a infection. In the two Phase-III studies involving treatment-naïve patients, among those with GT-1a receiving Olysio who had the Q80K polymorphism, 58% achieved SVR12 vs. 84% of patients without the Q80K polymorphism. In the placebo arm, 52% of patients with the Q80K polymorphism achieved SVR12. Prior-relapser patients also showed a reduced effect.
"Regarding Q80K, Janssen has long been committed to patient education and plans to make information about resistance testing available to providers," added Stoltz. "This includes details regarding the availability of NS3 sequencing testing and referring them to the diagnostic companies for specific questions about the tests that are offered."
The issue could, nevertheless, impact the new drug's market share. Gilead's much-anticipated NS5B inhibitor sofosbuvir, now awaiting approval with a PDUFA date of December 8, 2013, is also expected to launch with a regimen that contains INF and RBV for GT-2 and GT-3 patients.
Gilead is expected to rack up more than 50% of the HCV market and at least $2.3 billion in global annual sales by 2016, according to an inThought forecast, possibly more depending on the extent of the treatable population. Olysio could still pick up $637 million in global annual sales in that timeframe, the analysts predict.
Of note, Gilead has studied an INF- and RBV-free combo of sofosbuvir + simeprevir in the COSMOS study, which included treatment naïve or previous null responder patients. The oral cocktail demonstrated SVR4 rates of 96% and 100% with or without RBV, respectively, as reported by inThought. Gilead, however, is likely to promote sofosbuvir with its own ledipasvir (GS-5885), an NS5A protein inhibitor, rather than with Olysio.
For J&J's part, in October it acquired an NS5A oral compound from GlaxoSmithKline called GSK805, which it will look to commercialize in its own all-oral regimen. “This combination would include a protease inhibitor, a non-nucleoside polymerase inhibitor, and an NS5a inhibitor, which is the same combination AbbVie is using in its ‘Aviator' combination of ABT-450/r + ABT-267 + ABT-333 with or without ribavirin,” wrote inThought. “These oral combinations, however, are missing a nucleoside NS5b inhibitor like Gilead's sofosbuvir.”
J&J will probably be late to the all-oral game behind Gilead and AbbVie, whose INF-free regimen is in Phase III. Second-wave companies also include Bristol-Myers Squibb and Merck.
http://www.mmm-online.com/jj-hcv-drug-okd-educational-push-planned/article/322612/
http://www.mmm-online.com/jj-hcv-drug-okd-educational-push-planned/article/322612/
HCV Viral Load at Baseline Sets Need for Protease Inhibitors
HCV Viral Load at Baseline Sets Need for Protease Inhibitors
Published: Nov 25, 2013
By Cole Petrochko, Staff Writer, MedPage Today
Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania
Hepatitis C genotype I patients with low viral load and sustained virologic response may be able to cut protease inhibitors from therapy, researchers found.
Among a cohort of treatment-naive, noncirrhosis hepatitis C patients with low viral load at baseline, those who achieved an undetectable viral load after 4 weeks of peginterferon alfa-2b and ribavirin had no significant differences in sustained viral load when continued on double-drug therapy versus triple-drug therapy that included a protease inhibitor, according to Brian Pearlman, MD, of the Center for Hepatitis C at the Atlanta Medical Center in Georgia, and Carole Ehleben, EdD, also of Atlanta Medical Center.
These similarities remained regardless of viral subtype -- genotypes 1a or 1b -- or interleukin 28b genotypes, as well as ethnicity (black versus white), they wrote online in the journal Hepatology.
Recent clinical trial data demonstrated the "near perfect cure rates" of a four-drug hepatitis C virus (HCV) treatment as part of the SAPPHIRE-1 study. Other all-oral treatments containing two- and three-drug combinations have also shown to be well tolerated and safe, with cure rates of 89% or greater.
The authors noted that the current standard of therapy for treatment-naive HCV genotype I patients is a triple therapy of peginterferon, ribavirin, and a protease inhibitor. They studied whether the inclusion of a protease inhibitor in such patients who achieve rapid virologic response after 4 weeks of peginterferon and ribavirin therapy was necessary. The study population included 233 patients with low HCV viral load at baseline who did not have cirrhosis.
Baseline characteristics the researchers recorded included age, sex, body mass index, fasting glucose, 25-hydroxyvitamin D levels, ethnicity, histological results of pretreatment liver biopsy, and quantitative HCV viral load. Patients were stratified by HCV genotype and interleukin-28b genotype.
Roughly half of the sample (48%) achieved rapid virologic response to the 4-week regimen, and these participants were randomized to either two- or three-drug therapy, with the three-drug group receiving 24 weeks of treatment and the two-drug group receiving 20 weeks of treatment.
At baseline and at monthly follow-up, researchers recorded participant's physical characteristics, weight, Beck's Depression Inventory, blood count and differential, hepatic profile, thyroid stimulating hormone, electrolytes, serum creatinine, serum uric acid, and serum beta-human chorionic gonadotropin testing.
In addition to virologic response, adverse event profiles were not significantly different between two- and three-drug groups, nor were dose reductions and discontinuation.
"Baseline patient ethnicity, viral subtype, and interleukin-28b genotype did not seem to impact sustained virologic response rates ultimately, regardless of therapy used," they concluded, adding that these findings amplify "the point that on-treatment predictors of therapy success trump pretreatment expectations."
They also noted that protease inhibitors "are costly, and are not yet available in many countries that lack the monetary resources to cover them," and that these findings may present a significant cost savings in at least those HCV patients with a low viral load.
They cautioned that their research was limited to patients who had a low viral load at baseline, and these results may not generalize to patients with a high viral load at baseline. In addition, the study was performed in a single center and had no formal statistical hypothesis testing.
Pearlman declared support from Merck
http://www.medpagetoday.com/Gastroenterology/Hepatitis/43114
Published: Nov 25, 2013
By Cole Petrochko, Staff Writer, MedPage Today
Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania
Hepatitis C genotype I patients with low viral load and sustained virologic response may be able to cut protease inhibitors from therapy, researchers found.
Among a cohort of treatment-naive, noncirrhosis hepatitis C patients with low viral load at baseline, those who achieved an undetectable viral load after 4 weeks of peginterferon alfa-2b and ribavirin had no significant differences in sustained viral load when continued on double-drug therapy versus triple-drug therapy that included a protease inhibitor, according to Brian Pearlman, MD, of the Center for Hepatitis C at the Atlanta Medical Center in Georgia, and Carole Ehleben, EdD, also of Atlanta Medical Center.
These similarities remained regardless of viral subtype -- genotypes 1a or 1b -- or interleukin 28b genotypes, as well as ethnicity (black versus white), they wrote online in the journal Hepatology.
Recent clinical trial data demonstrated the "near perfect cure rates" of a four-drug hepatitis C virus (HCV) treatment as part of the SAPPHIRE-1 study. Other all-oral treatments containing two- and three-drug combinations have also shown to be well tolerated and safe, with cure rates of 89% or greater.
The authors noted that the current standard of therapy for treatment-naive HCV genotype I patients is a triple therapy of peginterferon, ribavirin, and a protease inhibitor. They studied whether the inclusion of a protease inhibitor in such patients who achieve rapid virologic response after 4 weeks of peginterferon and ribavirin therapy was necessary. The study population included 233 patients with low HCV viral load at baseline who did not have cirrhosis.
Baseline characteristics the researchers recorded included age, sex, body mass index, fasting glucose, 25-hydroxyvitamin D levels, ethnicity, histological results of pretreatment liver biopsy, and quantitative HCV viral load. Patients were stratified by HCV genotype and interleukin-28b genotype.
Roughly half of the sample (48%) achieved rapid virologic response to the 4-week regimen, and these participants were randomized to either two- or three-drug therapy, with the three-drug group receiving 24 weeks of treatment and the two-drug group receiving 20 weeks of treatment.
At baseline and at monthly follow-up, researchers recorded participant's physical characteristics, weight, Beck's Depression Inventory, blood count and differential, hepatic profile, thyroid stimulating hormone, electrolytes, serum creatinine, serum uric acid, and serum beta-human chorionic gonadotropin testing.
In addition to virologic response, adverse event profiles were not significantly different between two- and three-drug groups, nor were dose reductions and discontinuation.
"Baseline patient ethnicity, viral subtype, and interleukin-28b genotype did not seem to impact sustained virologic response rates ultimately, regardless of therapy used," they concluded, adding that these findings amplify "the point that on-treatment predictors of therapy success trump pretreatment expectations."
They also noted that protease inhibitors "are costly, and are not yet available in many countries that lack the monetary resources to cover them," and that these findings may present a significant cost savings in at least those HCV patients with a low viral load.
They cautioned that their research was limited to patients who had a low viral load at baseline, and these results may not generalize to patients with a high viral load at baseline. In addition, the study was performed in a single center and had no formal statistical hypothesis testing.
Pearlman declared support from Merck
http://www.medpagetoday.com/Gastroenterology/Hepatitis/43114
Hepatitis C-A third agent that acts directly against the virus has been approved
New HCV Drug Approved
Published: Nov 25, 2013
A third agent that acts directly against hepatitis C (HCV) has been approved, according to the company that makes the drug.
But simeprevir (Olysio) -- an NS3/4A protease inhibitor intended to be used in combination with two standard HCV medications, pegylated interferon, and ribavirin -- is the first such agent that can be taken once a day, Janssen Therapeutics said in a release.
The other two protease inhibitors to win approval -- telaprevir (Incivek) and boceprevir (Victrelis) -- got the nod in 2011.
Simeprevir is approved for genotype 1 infected adults with compensated liver disease, including cirrhosis, the company release said. The move was expected, after an advisory board in October voted unanimously in favor of approval. The FDA usually follows such advice, although it is not obliged to do so.
The three protease inhibitors are the leading edge of a wave of so-called direct-acting agents, or DAAs, that target aspects of HCV replication. In contrast, ribavirin is a general anti-viral agent and interferon works by boosting the immune system.
Simeprevir, combined with interferon and ribavirin, yielded solid results in various patient groups, where cure was defined as undetectable virus 12 or 24 weeks after the end of therapy (SVR12 or SVR24):
For both treatment-naive patients and those who had relapsed, the drug is recommended to be used for 12 weeks, combined with 24 weeks of interferon and ribavirin.
For those whose previous response was partial or null, a treatment regimen of 12 weeks, combined with 48 weeks of interferon and ribavirin, is recommended.
The efficacy of the drug is "greatly decreased" in patients whose virus has the so-called Q80K polymorphism in the protease gene, the company noted, urging that patients discuss the issue of testing for the variant with their doctors and choose a different therapy if Q80K is present.
Despite that limitation, the approval is "an important milestone," according to Douglas Dieterich, MD, of Mount Sinai School of Medicine in New York City, who was involved in the simeprevir clinical trials.
"It means that patients have a new treatment option with the potential to cure this challenging disease," he said in the release.
http://www.medpagetoday.com/Gastroenterology/Hepatitis/43101
Published: Nov 25, 2013
A third agent that acts directly against hepatitis C (HCV) has been approved, according to the company that makes the drug.
But simeprevir (Olysio) -- an NS3/4A protease inhibitor intended to be used in combination with two standard HCV medications, pegylated interferon, and ribavirin -- is the first such agent that can be taken once a day, Janssen Therapeutics said in a release.
The other two protease inhibitors to win approval -- telaprevir (Incivek) and boceprevir (Victrelis) -- got the nod in 2011.
Simeprevir is approved for genotype 1 infected adults with compensated liver disease, including cirrhosis, the company release said. The move was expected, after an advisory board in October voted unanimously in favor of approval. The FDA usually follows such advice, although it is not obliged to do so.
The three protease inhibitors are the leading edge of a wave of so-called direct-acting agents, or DAAs, that target aspects of HCV replication. In contrast, ribavirin is a general anti-viral agent and interferon works by boosting the immune system.
Simeprevir, combined with interferon and ribavirin, yielded solid results in various patient groups, where cure was defined as undetectable virus 12 or 24 weeks after the end of therapy (SVR12 or SVR24):
- Among treatment-naive patients, 80% of those getting simeprevir, along with interferon and ribavirin, achieved SVR12, compared with 50% of those getting interferon and ribavirin plus a placebo.
- Among those who had relapsed after previous treatment with interferon and ribavirin, SVR12 rates were 79% in the simeprevir group and 37% in the placebo group.
- Among patients who had only partly responded to previous therapy with interferon and ribavirin, simeprevir-based treatment led to undetectable virus 24 weeks after the end of treatment (SVR24) in 65%, compared with 9% in the placebo group.
- And among patients who had not responded at all to previous treatment with interferon and ribavirin, 53% reached SVR24 on simeprevir-based therapy, compared with 19% in the placebo group.
For both treatment-naive patients and those who had relapsed, the drug is recommended to be used for 12 weeks, combined with 24 weeks of interferon and ribavirin.
For those whose previous response was partial or null, a treatment regimen of 12 weeks, combined with 48 weeks of interferon and ribavirin, is recommended.
The efficacy of the drug is "greatly decreased" in patients whose virus has the so-called Q80K polymorphism in the protease gene, the company noted, urging that patients discuss the issue of testing for the variant with their doctors and choose a different therapy if Q80K is present.
Despite that limitation, the approval is "an important milestone," according to Douglas Dieterich, MD, of Mount Sinai School of Medicine in New York City, who was involved in the simeprevir clinical trials.
"It means that patients have a new treatment option with the potential to cure this challenging disease," he said in the release.
http://www.medpagetoday.com/Gastroenterology/Hepatitis/43101
New Video: Hepatitis C Drug OLYSIO™ (simeprevir)
New Video: Hepatitis C Drug OLYSIO™ (simeprevir)
Related
OLYSIO™ (simeprevir) Receives FDA Approval
HCV Drug Olysio (simeprevir) - The New Kid On The Block
OLYSIO Website
Prescribing Information
Patient Information
Important Safety Information
Simeprevir and Sofosbuvir-The Next Wave of Hepatitis C Treatment
New Video: Hepatitis C Drug OLYSIO™ (simeprevir)
*Audio begins after introduction
Related
OLYSIO™ (simeprevir) Receives FDA Approval
HCV Drug Olysio (simeprevir) - The New Kid On The Block
OLYSIO Website
Prescribing Information
Patient Information
Important Safety Information
Simeprevir and Sofosbuvir-The Next Wave of Hepatitis C Treatment
New Video: Hepatitis C Drug OLYSIO™ (simeprevir)
*Audio begins after introduction
Sunday, November 24, 2013
HCV Drug Olysio (simeprevir) - The New Kid On The Block
HCV Drug Olysio (simeprevir) - The New Kid On The Block
Hello everyone,
It sure is another cold weekend here in Michigan, hope it's warmer in your part of the world.
Today, as I sat cuddled in my warm chair, gazing out the window, I found myself watching the birds on our backyard feeder. One seed at a time, slowly they ate their afternoon meal. This arduous task ensures their survival, and will continue day in and day out, season after season.
The same can be said of hepatitis C patients, waiting day after day, year after year for new therapies to be approved. In some cases, the drugs are needed for patients to remain healthy, and yes, for others, they are needed for survival.
The HCV standard-of-care treatment in 2001 was the combination of pegylated interferon and ribavirin. Unfortunately this treatment only cured around 50% of individuals with genotype 1, which is the most prevalent HCV genotype in the US and Europe. The HCV community waited ten years before a new drug was available, finally, in 2011 the first direct-acting antivirals (DAAs) boceprevir and telaprevir received FDA approval.
Two years later, and some 48 hours ago, the FDA approved Olysio (simeprevir), a new drug to treat HCV.
On this special occasion, and for the newly diagnosed, I thought a few links for reference purposes and a bit of information on simeprevir may be helpful.
Check back often, as new updates are available links and information will be provided below;
December 5-3 Updates
Simeprevir (Olysio): J & J Patient Access Programs
Video - Dr. Joseph Galati talks about HCV drug OLYSIO (simeprevir)
Olysio (simeprevir) - Resistant Variant (Q80K)
Although, simeprevir appears to be slightly more effective than the standard of care, curing 80 percent of treatment-naïve patients, and easier to take, there are some drawbacks. Before starting simeprevir patients with HCV genotype 1a need to be screened for a genetic mutation called Q80K polymorphism.
November 26th updates: An article written by Marc Iskowitz on the cost of OLYSIO and an educational video from Janssen
OLYSIO (Simeprevir) Cost?
Janssen has priced Olysio at a wholesale acquisition price of $22,120 per bottle of 28 capsules (150 mg capsules), which is an approximately one-month supply. That's roughly $66,360 for a three-month course.
Read more here...
Video
Hepatitis C Drug OLYSIO™ (simeprevir)
The Basics
OLYSIO (Simeprevir) - The New Kid On The Block
Simeprevir is used to treat HCV genotype 1 infected subjects with compensated liver disease (including cirrhosis) in combination with peginterferon and ribavirin. Simeprevir has yet to be studied in patients who have previously failed therapy with a treatment regimen that includes other HCV protease inhibitors.
Before starting simeprevir patients with HCV genotype 1a should be screened for a genetic mutation called Q80K polymorphism. Alternative therapy should be considered for people with the mutation according to Prescribing Information.
Like Simeprevir, both boceprevir and telaprevir are protease inhibitors approved to treat HCV genotype 1 patients in combination with peginterferon and ribavirin.
Simeprevir and telaprevir are used for 12 weeks, boceprevir is used from 24 to 44 weeks.
Peginterferon and ribavirin are used with these drugs, from 24 to 48 weeks.
Simeprevir Duration of Treatment
The recommended duration of treatment with OLYSIO is 12 weeks in combination with peginterferon alfa and ribavirin. In all patients, treatment with OLYSIO should be initiated in combination with peginterferon alfa and ribavirin and should be administered for 12 weeks.
All treatment - naïve and prior relapser patients , including those with cirrhosis , should receive an additional 12 weeks of peginterferon alfa and ribavirin after completing 12 weeks of treatment with OLYSIO , peginterferon alfa and ribavirin (total treatment duration of 24 weeks)
All prior non - responder patients (including partial and null - responder s), including those with cirrhosis, should receive an additional 36 weeks of peginterferon alfa and ribavirin after completing 12 weeks of treatment with OLYSIO, peginterferon alfa and ribavirin (total treatment duration of 48 weeks)
The good news? Simeprevir is taken only once daily (capsule of 150 mg taken orally) with food.
*The type of food does not affect exposure to simeprevir. The capsule should be swallowed as a whole.
Boceprevir and telaprevir are both taken three times a day with a meal or snack, telaprevir should be taken with a snack that contains protein (cheese, peanut butter, eggs). Although, in some patients telaprevir can be taken twice daily.
Lesson Learned
Telaprevir and boceprevir have significantly increased the ability to cure HCV, but both PIs have their own side effects, including those from interferon.
An important lesson we learned from these drugs may serve as a reminder for future DDAs, that is, once telaprevir and boceprevir were used in larger groups of patients, or in "real-life" settings - outside clinical trials, new response rates and adverse effects began to emerge.
For instance Dr. Arpita Sheth presented a poster at the Interscience Conference which found 30% of veterans taking direct-acting antivirals boceprevir and telaprevir in "real-life" settings, discontinued treatment by week 24, despite high rates of early response. The study included a greater proportion of cirrhotic patients, then compared to clinical trials. Anemia was increased by 15% - over what has been reported elsewhere. The study appears in the 2013 August issue of Clinical Gastroenterology and Hepatology
Food For Thought
In an editorial, in which both simeprevir and sofosbuvir were the topic, researchers wrote; Time will tell if these first second wave DAA agents will prove to be safe and effective when used in large numbers of real life chronic HCV infected patients. The article was published in the November, December issue of Annals Of Hepatology.
Simeprevir Side Effects
Common side effects reported in clinical trials were rash, itching, and nausea, some patients experienced serious photosensitivity reactions which required a trip to the hospital.
The FDA’s advisory panel determined simeprevir was much easier to take than the first generation protease inhibitors (PIs) telaprevir and boceprevir. With SVR rates of 79%-80% in phase III studies and an impressive risk profile the drug was unanimously supported by the panel and approved by the FDA.
In the above mentioned editorial researchers agreed, both simeprevir and sofosbuvir, had a better safety profile and comparable, if not higher, efficacy then telaprevir and boceprevir. However,
In an article written by Elizabeth Mechcatie, the side effects reported in the simeprevir phase III trials included;
Download the FDA review package for simeprevir and Johnson & Johnson document released Oct 23.
Drug-drug interactions
The complexity of managing drug–drug interactions is another similarity shared by the PIs. A study in the December 2013 issue of Alimentary Pharmacology & Therapeutics, investigating drug–drug interactions in patients using telaprevir and boceprevir reported; Drug–drug interactions between a PI and drugs newly prescribed during anti-viral therapy were considerable in 42% of the patients.
Other medications used while treating with telaprevir and boceprevir can interfere with the way DDAs are metabolized. The drug–drug interactions can either increase drug concentrations which may cause toxicity and lead to side effects, or decrease drug concentrations leading to a loss of efficacy, and, if the PIs are affected, this may lead to treatment failure due to emergence of viral resistance and subsequently a virological breakthrough.
An excerpt from the study;
Simeprevir has a list of medications that can cause drug–drug interactions as well, those medications along with patient and prescribing information, can be found online at http://www.olysio.com/intro/.
Let this be an important reminder folks, to ensure a safe, successful treatment plan, provide a complete health history to your healthcare provider and include a list of all medications, vitamins, or herbs you are taking before and during HCV therapy. Going forward, treating with new agents, the importance of preparing for treatment can not be underestimated, communicating with your physician or treatment nurse is key to a promising outcome.
Simeprevir
Sustained Virologic Response - SVR
The results from three phase III studies used to determine the FDA approval of simeprevir were QUEST-1 and QUEST-2, made up of treatment-naïve patients. In PROMISE patients relapsed after prior interferon-based treatment – as well as data from the Phase 2b ASPIRE study in prior non-responder patients.
QUEST-1 and QUEST-2
In the two studies deemed QUEST-1 and QUEST-2, of 785 treatment-naive patients, 80 percent of those treated with simeprevir achieved sustained virologic response 12 weeks after the end of treatment, called SVR12, compared with 50 percent in the placebo groups.
PROMISE
In the third study called PROMISE of 393 prior-relapsers, 79 percent in the simeprevir group achieved SVR12 compared with 37 percent of patients in the placebo group.
ASPIRE
Results from ASPIRE led to sustained virologic response 24 weeks after the end of treatment (SVR24) in 65 percent of prior partial-responder patients and 53 percent of prior-null responder patients compared with 9 percent and 19 percent of prior partial- and null-responder patients in the placebo groups, respectively.
Links
OLYSIO Website
Simeprevir (Olysio): J & J Patient Access Programs
Prescribing Information
Patient Information
Important Safety Information
With great anticipation we patiently await for the approval of sofosbuvir, a nucleotide analog NS5B polymerase inhibitor. The FDA approval is expected to be announced in early December. Sofosbuvir will be used only with ribavirin, for treating adult HCV genotypes 2 and 3. However, in HCV genotype 1 and 4 treatment-naive patients, sofosbuvir will be used in combination with pegylated interferon and ribavirin.
Off Label Use - Simeprevir and Sofosbuvir
Paul Sax, Editor-in-Chief at NEJM Journal Watch wrote an article this past summer; Both Simeprevir and Sofosbuvir Likely Approved by 2014 - Clinical/Ethical/Pharmacoeconomic Dilemmas Loom on the possibility of combining simeprevir and sofosbuvir with or without ribavirin, to create an off label interferon-free regimen;
Continue reading...
I hate to be redundant, but once again, in the editorial discussing simeprevir and sofosbuvir, I noticed the mention of off label use combining simeprevir and sofosbuvir;
Continue reading...
Once sofosbuvir is FDA approved I assume we will be reading more on off label use, as is often the case, the patient is the last to know.
Other then simeprevir and sofosbuvir, there are many additional potent agents in the clinical pipeline. AbbVie reported this month an interferon-free combination of three drugs plus ribavirin achieved a sustained virologic response (SVR12) in 96 percent of previously untreated genotype 1 patients.
I am determined to remain optimistic that in the future, interferon-free regimens will provide safe and effective therapy in all different HCV infected patient populations.
Stay healthy and positive.
Hello everyone,It sure is another cold weekend here in Michigan, hope it's warmer in your part of the world.
Today, as I sat cuddled in my warm chair, gazing out the window, I found myself watching the birds on our backyard feeder. One seed at a time, slowly they ate their afternoon meal. This arduous task ensures their survival, and will continue day in and day out, season after season.
The same can be said of hepatitis C patients, waiting day after day, year after year for new therapies to be approved. In some cases, the drugs are needed for patients to remain healthy, and yes, for others, they are needed for survival.
The HCV standard-of-care treatment in 2001 was the combination of pegylated interferon and ribavirin. Unfortunately this treatment only cured around 50% of individuals with genotype 1, which is the most prevalent HCV genotype in the US and Europe. The HCV community waited ten years before a new drug was available, finally, in 2011 the first direct-acting antivirals (DAAs) boceprevir and telaprevir received FDA approval.
Two years later, and some 48 hours ago, the FDA approved Olysio (simeprevir), a new drug to treat HCV.
On this special occasion, and for the newly diagnosed, I thought a few links for reference purposes and a bit of information on simeprevir may be helpful.
Check back often, as new updates are available links and information will be provided below;
December 5-3 Updates
Simeprevir (Olysio): J & J Patient Access Programs
Video - Dr. Joseph Galati talks about HCV drug OLYSIO (simeprevir)
Olysio (simeprevir) - Resistant Variant (Q80K)
Although, simeprevir appears to be slightly more effective than the standard of care, curing 80 percent of treatment-naïve patients, and easier to take, there are some drawbacks. Before starting simeprevir patients with HCV genotype 1a need to be screened for a genetic mutation called Q80K polymorphism.
November 26th updates: An article written by Marc Iskowitz on the cost of OLYSIO and an educational video from Janssen
OLYSIO (Simeprevir) Cost?
Janssen has priced Olysio at a wholesale acquisition price of $22,120 per bottle of 28 capsules (150 mg capsules), which is an approximately one-month supply. That's roughly $66,360 for a three-month course.
Read more here...
Video
Hepatitis C Drug OLYSIO™ (simeprevir)
The Basics
OLYSIO (Simeprevir) - The New Kid On The Block
Simeprevir is used to treat HCV genotype 1 infected subjects with compensated liver disease (including cirrhosis) in combination with peginterferon and ribavirin. Simeprevir has yet to be studied in patients who have previously failed therapy with a treatment regimen that includes other HCV protease inhibitors.
Before starting simeprevir patients with HCV genotype 1a should be screened for a genetic mutation called Q80K polymorphism. Alternative therapy should be considered for people with the mutation according to Prescribing Information.
Like Simeprevir, both boceprevir and telaprevir are protease inhibitors approved to treat HCV genotype 1 patients in combination with peginterferon and ribavirin.
Simeprevir and telaprevir are used for 12 weeks, boceprevir is used from 24 to 44 weeks.
Peginterferon and ribavirin are used with these drugs, from 24 to 48 weeks.
Simeprevir Duration of Treatment
The recommended duration of treatment with OLYSIO is 12 weeks in combination with peginterferon alfa and ribavirin. In all patients, treatment with OLYSIO should be initiated in combination with peginterferon alfa and ribavirin and should be administered for 12 weeks.
All treatment - naïve and prior relapser patients , including those with cirrhosis , should receive an additional 12 weeks of peginterferon alfa and ribavirin after completing 12 weeks of treatment with OLYSIO , peginterferon alfa and ribavirin (total treatment duration of 24 weeks)
All prior non - responder patients (including partial and null - responder s), including those with cirrhosis, should receive an additional 36 weeks of peginterferon alfa and ribavirin after completing 12 weeks of treatment with OLYSIO, peginterferon alfa and ribavirin (total treatment duration of 48 weeks)
The good news? Simeprevir is taken only once daily (capsule of 150 mg taken orally) with food.
*The type of food does not affect exposure to simeprevir. The capsule should be swallowed as a whole.
Boceprevir and telaprevir are both taken three times a day with a meal or snack, telaprevir should be taken with a snack that contains protein (cheese, peanut butter, eggs). Although, in some patients telaprevir can be taken twice daily.
Lesson Learned
Telaprevir and boceprevir have significantly increased the ability to cure HCV, but both PIs have their own side effects, including those from interferon.
An important lesson we learned from these drugs may serve as a reminder for future DDAs, that is, once telaprevir and boceprevir were used in larger groups of patients, or in "real-life" settings - outside clinical trials, new response rates and adverse effects began to emerge.
For instance Dr. Arpita Sheth presented a poster at the Interscience Conference which found 30% of veterans taking direct-acting antivirals boceprevir and telaprevir in "real-life" settings, discontinued treatment by week 24, despite high rates of early response. The study included a greater proportion of cirrhotic patients, then compared to clinical trials. Anemia was increased by 15% - over what has been reported elsewhere. The study appears in the 2013 August issue of Clinical Gastroenterology and Hepatology
Food For Thought
In an editorial, in which both simeprevir and sofosbuvir were the topic, researchers wrote; Time will tell if these first second wave DAA agents will prove to be safe and effective when used in large numbers of real life chronic HCV infected patients. The article was published in the November, December issue of Annals Of Hepatology.
Simeprevir Side Effects
Common side effects reported in clinical trials were rash, itching, and nausea, some patients experienced serious photosensitivity reactions which required a trip to the hospital.
The FDA’s advisory panel determined simeprevir was much easier to take than the first generation protease inhibitors (PIs) telaprevir and boceprevir. With SVR rates of 79%-80% in phase III studies and an impressive risk profile the drug was unanimously supported by the panel and approved by the FDA.
In the above mentioned editorial researchers agreed, both simeprevir and sofosbuvir, had a better safety profile and comparable, if not higher, efficacy then telaprevir and boceprevir. However,
In an article written by Elizabeth Mechcatie, the side effects reported in the simeprevir phase III trials included;
In phase III studies fatigue, headache, and influenza like illness, associated with PR, were the most common adverse events. The only deaths reported were in three patients treated with simeprevir after they stopped taking the drug, but were not considered related to the drug. During the first 12 weeks of treatment, dyspnea was also higher among those on simeprevir (12% vs. 8%), but so far, the cause has not been determined, according to the FDA reviewer. Hyperbilirubinemia was also higher among those on simeprevir (49% vs. 26%), mostly grade 1 and 2 abnormalities.
In the first 12 weeks in the phase III studies, rashes (including photosensitivity) were reported in 28% of those on simeprevir, vs. 20% of those on PR only. Pruritus was also more common among those on simeprevir (22% vs. 15%); 1% of patients discontinued treatment because of a rash.
Download the FDA review package for simeprevir and Johnson & Johnson document released Oct 23.
Drug-drug interactions
The complexity of managing drug–drug interactions is another similarity shared by the PIs. A study in the December 2013 issue of Alimentary Pharmacology & Therapeutics, investigating drug–drug interactions in patients using telaprevir and boceprevir reported; Drug–drug interactions between a PI and drugs newly prescribed during anti-viral therapy were considerable in 42% of the patients.
Other medications used while treating with telaprevir and boceprevir can interfere with the way DDAs are metabolized. The drug–drug interactions can either increase drug concentrations which may cause toxicity and lead to side effects, or decrease drug concentrations leading to a loss of efficacy, and, if the PIs are affected, this may lead to treatment failure due to emergence of viral resistance and subsequently a virological breakthrough.
An excerpt from the study;
The next wave of DAAs including the protease inhibitors faldaprevir and simeprevir as well as the NS5B nucleotide inhibitor sofosbuvir may be available in early 2014 and more will follow in the upcoming years.
Risk for DDIs differ between the various future DAA classes. The nucleotide NS5B inhibitor sofosbuvir does not seem to be involved in significant DDIs.[24, 25] In contrast, DDIs have to be considered for several nonnucleotide NS5B inhibitors.[15] DDIs may also play a role for some NS5A inhibitors. Daclatasvir is substrate and inhibitor of P-glycoprotein and substrate of CYP3A4. However, pharmacokinetic data suggest that risk for significant DDIs is far lower compared with using protease inhibitors.[15]
Soon-available PIs faldaprevir and simeprevir are also both inhibitors and substrates of CYP3A4 and it has already been shown that drug levels are altered in the presence of other strong inhibitors or inducers of CYP3A4.[15] Taken together, it can be assumed that the challenge of DDIs will certainly accompany HCV therapy in upcoming years, in particular, as combination treatments with several DAAs will most likely be necessary to finally achieve an efficient interferon-free anti-viral treatment.[6, 26]Continue to the full text @ Alimentary Pharmacology & Therapeutics
Simeprevir has a list of medications that can cause drug–drug interactions as well, those medications along with patient and prescribing information, can be found online at http://www.olysio.com/intro/.
Let this be an important reminder folks, to ensure a safe, successful treatment plan, provide a complete health history to your healthcare provider and include a list of all medications, vitamins, or herbs you are taking before and during HCV therapy. Going forward, treating with new agents, the importance of preparing for treatment can not be underestimated, communicating with your physician or treatment nurse is key to a promising outcome.
Simeprevir
Sustained Virologic Response - SVR
The results from three phase III studies used to determine the FDA approval of simeprevir were QUEST-1 and QUEST-2, made up of treatment-naïve patients. In PROMISE patients relapsed after prior interferon-based treatment – as well as data from the Phase 2b ASPIRE study in prior non-responder patients.
QUEST-1 and QUEST-2
In the two studies deemed QUEST-1 and QUEST-2, of 785 treatment-naive patients, 80 percent of those treated with simeprevir achieved sustained virologic response 12 weeks after the end of treatment, called SVR12, compared with 50 percent in the placebo groups.
PROMISE
In the third study called PROMISE of 393 prior-relapsers, 79 percent in the simeprevir group achieved SVR12 compared with 37 percent of patients in the placebo group.
ASPIRE
Results from ASPIRE led to sustained virologic response 24 weeks after the end of treatment (SVR24) in 65 percent of prior partial-responder patients and 53 percent of prior-null responder patients compared with 9 percent and 19 percent of prior partial- and null-responder patients in the placebo groups, respectively.
Links
OLYSIO Website
Simeprevir (Olysio): J & J Patient Access Programs
Prescribing Information
Patient Information
Important Safety Information
With great anticipation we patiently await for the approval of sofosbuvir, a nucleotide analog NS5B polymerase inhibitor. The FDA approval is expected to be announced in early December. Sofosbuvir will be used only with ribavirin, for treating adult HCV genotypes 2 and 3. However, in HCV genotype 1 and 4 treatment-naive patients, sofosbuvir will be used in combination with pegylated interferon and ribavirin.
Off Label Use - Simeprevir and Sofosbuvir
Paul Sax, Editor-in-Chief at NEJM Journal Watch wrote an article this past summer; Both Simeprevir and Sofosbuvir Likely Approved by 2014 - Clinical/Ethical/Pharmacoeconomic Dilemmas Loom on the possibility of combining simeprevir and sofosbuvir with or without ribavirin, to create an off label interferon-free regimen;
The interim results of the COSMOS study, presented at CROI this year, showed a >90% cure rate in 80 prior null responders (no cirrhosis) who received simeprevir and sofosbuvir together for 12 or 24 weeks, with and without ribavirin. There was no interferon in this study. (The full slide set of the presentation is on NATAP.)
So if these two drugs are both approved as expected, one could easily make the case that the best treatment for HCV genotype 1 — in terms of efficacy, safety, tolerability, pretty much everything except drug-drug interactions and cost — will be the COSMOS regimen of simeprevir and sofosbuvir, with or without ribavirin. And emphatically without interferon.
And that, my dear friends, is off-label use.
Continue reading...
I hate to be redundant, but once again, in the editorial discussing simeprevir and sofosbuvir, I noticed the mention of off label use combining simeprevir and sofosbuvir;
THE FIRST ALL ORAL INTERFERON-FREE COMBINATION OUTSIDE CLINICAL TRIALS:OFF-LABEL
USE OF SIMEPREVIR PLUS SOFOSBUVIR?
As soon as simeprevir and sofosbuvir become commercially available, it is possible that some people will entertain the possibility of combining both agents with our without RBV, to create an off label IFN free regimen. In this regard, it is important to review the results of the COSMOS study.23 This Phase 2 exploratory trial enrolled two cohorts of HCV genotype 1 null responders:one with fibrosis stage Metavir F0-F2 and the other with F3-F4. Both cohorts were randomized to receive simeprevir plus sofosbuvir with or without RBV for 12 vs. 24 weeks of fixed therapy duration.
Preliminary results are so far available only for the12 week arm of the first cohort, with less significant liver fibrosis. Among 27 patients that received simeprevir plus sofosbuvir with RBV, the rate of undetectable HCV RNA 8 weeks after the end of therapy (SVR-8) was 96%. Similarly, among 14patients treated with simeprevir plus sofosbuvir without RBV, SVR-8 was 93%. Overall, 24 patients already reached 12 weeks of follow-up after the end of therapy and all maintain undetectable HCV RNA(SVR-12). Eight patients reached week 24 follow up after the end of therapy and also remain HCV RNA undetectable (SVR-24). Only 2% of patients had to interrupt prematurely the trial for adverse events.These results are surely preliminary, however the message they send out is powerful: in some areas of the world we may start to see the first IFN free regimens already being used to treat chronic HCV patients in routine clinical practice as early as 2014.
Continue reading...
Once sofosbuvir is FDA approved I assume we will be reading more on off label use, as is often the case, the patient is the last to know.
Other then simeprevir and sofosbuvir, there are many additional potent agents in the clinical pipeline. AbbVie reported this month an interferon-free combination of three drugs plus ribavirin achieved a sustained virologic response (SVR12) in 96 percent of previously untreated genotype 1 patients.
I am determined to remain optimistic that in the future, interferon-free regimens will provide safe and effective therapy in all different HCV infected patient populations.
Stay healthy and positive.
Friday, November 22, 2013
OLYSIO™ (simeprevir) Receives FDA Approval for Combination Treatment of Chronic Hepatitis C
Related:
HCV Drug Olysio (simeprevir) - The New Kid On The Block
OLYSIO Website
Prescribing Information
Patient Information
Important Safety Information
Simeprevir and Sofosbuvir-The Next Wave of Hepatitis C Treatment
U.S. FDA approves J&J hepatitis C pill
Reuters) - U.S. regulators on Friday approved the use of Johnson & Johnson's Olysio, also known as simeprevir, as a treatment for chronic infection with the liver-destroying hepatitis C virus.
Olysio, a protease inhibitor that blocks a specific protein needed by the virus to replicate, is to be used in combination with interferon, given by injection, and ribavirin, another pill.
Hepatitis C affects about 3.2 million Americans, killing more than 15,000 each year, mostly from illnesses such as cirrhosis and liver cancer.
The often-undiagnosed virus is transmitted through contaminated blood. Infection rates have dropped since the early 1990s, due in part to the introduction of blood and organ screening. Still, many older adults remain at risk, according to the Centers for Disease Control and Prevention, which has called for baby boomers to be routinely tested for the virus.
Olysio is a member of the same class of drugs as Merck & Co's Victrelis and Vertex Pharmaceuticals' Incivek. The FDA approved both those drugs in 2011.
Olysio was shown in clinical trials to cure patients with a shorter duration of treatment.
Drugmakers have been racing to develop more effective, easier-to-tolerate antivirals to treat hepatitis C. Wall Street analysts have forecast annual sales of billions of dollars for new drugs that would allow doctors to skip use of interferon, which can cause severe flu-like side effects.
The FDA is slated to decide by December 8 on Gilead Sciences' application for sofosbuvir, a member of a different class known as nucleotide analogue inhibitors, or "nukes," designed to block a different enzyme the virus needs to copy itself.
European regulators on Friday recommended approval of the Gilead drug, under the brand name Sovaldi.
Other companies working to develop new hepatitis C drugs include AbbVie and Bristol-Myers Squibb.
(Reporting By Deena Beasley)
Press Release
OLYSIO™ (simeprevir) Receives FDA Approval for Combination Treatment of Chronic Hepatitis C
OLYSIOTM is the first once-daily protease inhibitor approved for the treatment of chronic hepatitis C in a combination antiviral regimen for adults with compensated liver disease
TITUSVILLE, N.J. (November 22, 2013) – Janssen Therapeutics, Division of Janssen Products, LP (Janssen), announced today the U.S. Food and Drug Administration (FDA) has approved OLYSIOTM (simeprevir), an NS3/4A protease inhibitor, for the treatment of chronic hepatitis C infection as part of an antiviral treatment regimen in combination with pegylated interferon and ribavirin in genotype 1 infected adults with compensated liver disease, including cirrhosis. OLYSIOTM may benefit patients with chronic hepatitis C, including those who are treatment naïve or who have failed prior interferon-based therapy.
Chronic hepatitis C is a blood-borne infectious disease of the liver that affects approximately 3.2 million people in the United States.
OLYSIOTM works by blocking the viral protease enzyme that enables the hepatitis C virus (HCV) to replicate in host cells. The goal of treatment for chronic hepatitis C is cure, also known as sustained virologic response (SVR), which is defined as undetectable levels of HCV in the patients’ blood 12 to 24 weeks after the end of treatment. For treatment-naïve and prior-relapser patients, a fixed treatment regimen of 12 weeks of OLYSIOTM combined with 24 weeks of pegylated interferon and ribavirin is recommended. For prior partial- and null-responder patients, a treatment regimen of 12 weeks of OLYSIOTM combined with 48 weeks of pegylated interferon and ribavirin is recommended.
“Given the complexity of the condition, OLYSIOTM was studied in a number of different patient populations, including individuals who have relapsed or failed to respond to previous treatments,” said Douglas Dieterich, M.D., Professor of Medicine in the Division of Liver Diseases, Mount Sinai School of Medicine, and OLYSIOTM clinical trial investigator. “The FDA approval of OLYSIOTM is an important milestone for people living with chronic hepatitis C as it means that patients have a new treatment option with the potential to cure this challenging disease.”
OLYSIOTM is a prescription medicine used with other antiviral medicines, pegylated interferon and ribavirin, to treat genotype 1 chronic hepatitis C in adults with stable liver problems. OLYSIOTM must not be taken alone. The efficacy of OLYSIOTM in combination with peginterferon and ribavirin is greatly decreased in patients who have genotype 1a Q80K. Please talk to your doctor about testing for genotype 1a Q80K and using a different therapy when genotype 1a Q80K is present. It is not known if OLYSIOTM is safe and effective in children under 18 years of age.
The New Drug Application (NDA) filed by Janssen Research & Development, LLC, for OLYSIOTM was based in part on efficacy and safety results from three pivotal Phase 3 studies – QUEST-1 and QUEST-2 in treatment-naïve patients and PROMISE in patients who have relapsed after prior interferon-based treatment – as well as data from the Phase 2b ASPIRE study in prior non-responder patients. Each of the studies evaluated OLYSIOTM dosed once daily in combination with pegylated interferon and ribavirin versus treatment with placebo plus pegylated interferon and ribavirin.
Results from a pooled analysis of QUEST-1 and QUEST-2 demonstrated that 80 percent of treatment-naïve patients in the group receiving OLYSIOTM achieved sustained virologic response 12 weeks after the end of treatment (SVR12), compared with 50 percent of patients in the placebo groups. In PROMISE, 79 percent of prior-relapser patients in the simeprevir group of the study achieved SVR12 compared with 37 percent of patients in the placebo group. Results from ASPIRE demonstrated that use of OLYSIOTM led to sustained virologic response 24 weeks after the end of treatment (SVR24) in 65 percent of prior partial-responder patients and 53 percent of prior-null responder patients compared with 9 percent and 19 percent of prior partial- and null-responder patients in the placebo groups, respectively.
In the QUEST-1 and QUEST-2 studies, among genotype 1a treatment-naïve patients receiving OLYSIOTM who had the Q80K polymorphism (a naturally occurring variation in the HCV NS3/4A protease enzyme), 58 percent achieved SVR12 versus 84 percent of patients without the Q80K polymorphism. In the placebo arm, 52 percent of patients with the Q80K polymorphism achieved SVR12. In the PROMISE study, among prior-relapser patients with the Q80K polymorphism who received OLYSIOTM, 47 percent achieved SVR12 versus 78 percent of patients without the polymorphism. In the placebo arm, 30 percent of patients with the Q80K polymorphism achieved SVR12.
“As an advocate working with the hepatitis C community, I’m pleased to know that Janssen has been working to make sure OLYSIOTM will be reasonably priced and available to the patients who need it,” said Sue Simon, President of the Hepatitis C Association. “It is notable that in addition to introducing a new treatment option for patients, Janssen is establishing comprehensive programs to support and assist patients in their treatment journey.”
Janssen has launched OLYSIOTM Support, a comprehensive support program designed in partnership with the HCV community to assist in the hepatitis C treatment journey so that patients and caregivers – and their healthcare providers – can focus on treatment. To register for OLYSIOTM Support or for additional information, please visit OLYSIO.com.
About OLYSIOTM (simeprevir)
OLYSIOTM (simeprevir) is an NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB and indicated in the U.S. for the treatment chronic hepatitis C infection in combination with pegylated interferon and ribavirin in HCV genotype 1 infected subjects with compensated liver disease, including cirrhosis.
Janssen is responsible for the global clinical development of OLYSIOTM and has exclusive, worldwide marketing rights, except in the Nordic countries. Medivir AB will retain marketing rights for OLYSIOTM in these countries under the marketing authorization held by Janssen-Cilag International NV. The treatment was approved in September 2013 in Japan under the trade name SOVRIADTM and in November 2013 in Canada under the trade name GALEXOSTM for the treatment of genotype 1 hepatitis C. A Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) in April 2013 by Janssen-Cilag International NV seeking approval of OLYSIOTM for the treatment of genotype 1 or genotype 4 chronic hepatitis C. To date, more than 3,700 patients have been treated with OLYSIOTM in clinical trials.
For additional information about OLYSIOTM, please visit www.OLYSIO.com
Important Safety Information
What is OLYSIO?
• OLYSIOTM (simeprevir) is a prescription medicine used with other antiviral medicines, peginterferon alfa and ribavirin, to treat genotype 1 chronic (lasting a long time) hepatitis C in adults with stable liver problems.
• OLYSIO must not be taken alone. The efficacy of OLYSIO in combination with peginterferon and ribavirin is greatly decreased in patients who have genotype 1a Q80K. Please talk to your doctor about testing for genotype 1a Q80K and using a different therapy when genotype 1a Q80K is present.
It is not known if OLYSIO is safe and effective in children under 18 years of age.
Important Safety Information
What is the most important information I should know and who should not take OLYSIO?
OLYSIO, in combination with peginterferon alfa and ribavirin may cause birth defects or death of your unborn baby. If you are pregnant or your sexual partner is pregnant, or plans to become pregnant, do not take these medicines. You or your sexual partner should not become pregnant while taking OLYSIO with peginterferon alfa and ribavirin and for 6 months after treatment is over.
Females and males must use two effective forms of birth control during treatment and for 6 months after treatment with OLYSIO, peginterferon alfa, and ribavirin combination therapy. Talk to your healthcare provider about forms of birth control that may be used during this time.
Females must have a pregnancy test before starting treatment with OLYSIO, peginterferon alfa, and ribavirin combination therapy, every month while being treated, and every month for 6 months after your treatment with OLYSIO, peginterferon alfa, and ribavirin combination therapy is over.
If you or your female sexual partner becomes pregnant while taking OLYSIO, peginterferon alfa, and ribavirin combination therapy or within 6 months after you stop taking these medicines, tell your healthcare provider right away. You or your healthcare provider should contact the Ribavirin Pregnancy Registry by calling 1-800-593-2214. The Ribavirin Pregnancy Registry collects information about what happens to mothers and their babies if the mother takes ribavirin while she is pregnant.
OLYSIO in combination with peginterferon alfa and ribavirin may cause rashes and skin reactions to sunlight. These rashes and skin reactions to sunlight can be severe and you may need to be treated in a hospital. Rashes and skin reactions to sunlight are most common during the first 4 weeks of treatment, but can happen at any time during treatment with OLYSIO, peginterferon alfa, and ribavirin combination therapy.
Use sunscreen, and wear a hat, sunglasses, and protective clothing when you will be exposed to sunlight during treatment with OLYSIO.
Limit sunlight exposure during treatment with OLYSIO
Avoid use of tanning beds, sunlamps, or other types of light therapy during treatment with OLYSIO.
Call your healthcare provider right away if you get any of the following symptoms:
burning, redness, swelling or blisters on your skin
mouth sores or ulcers red or inflamed eyes, like “pink eye” (conjunctivitis)
Do not take OLYSIO alone. OLYSIO should be used together with peginterferon alfa and ribavirin to treat chronic hepatitis C infection.
What should I tell my healthcare provider before taking OLYSIO?
Before taking OLYSIO, tell your healthcare provider if you:
have liver problems other than hepatitis C virus infection
have taken the medicines telaprevir (Incivek®) or boceprevir (Victrelis®)
had a liver transplant
are receiving phototherapy
have any other medical condition
are of East Asian descent
are breastfeeding. It is not known if OLYSIO passes into your breast milk. You and your healthcare provider should decide if you will take OLYSIO or breastfeed. You should not do both.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
OLYSIO and other medicines may affect each other. This can cause you to have too much or not enough OLYSIO or other medicines in your body, which may affect the way OLYSIO or your other medicines work, or may cause side effects. Do not start taking a new medicine without telling your healthcare provider or pharmacist.
Especially tell your healthcare provider if you take any of the following medicines: amiodarone (Cordarone®, Pacerone®), amlodipine (Norvasc®), atazanavir (Reyataz®), atorvastatin (Lipitor®, Caduet®), carbamazepine (Carbatrol®, Epitol®, Equetro®, Tegretol®), cisapride (Propulsid®, Propulsid Quicksolv®), clarithromycin (Biaxin®, Prevpac®), cobicistat-containing medicine: (Stribild®), cyclosporine (Gengraf®, Neoral®, Sandimmune®), darunavir (Prezista®), delavirdine mesylate (Rescriptor®), dexamethasone (when administered by injection or when taken by mouth), digoxin (Lanoxin®), diltiazem (Cardizem®, Dilacor XR®, Tiazac®), disopyramide (Norpace®), efavirenz (Sustiva®, Atripla®), erythromycin (E.E.S.®, Eryc®, Ery-Tab®, Erythrocin®, Erythrocin Stearate®), etravirine (Intelence®), felodipine (Plendil®), flecainide (Tambocor®), fluconazole (when taken by mouth or when administered by injection) (Diflucan®), fosamprenavir (Lexiva®), indinavir (Crixivan®), itraconazole (when taken by mouth) (Sporanox®, Onmel®), ketoconazole (when taken by mouth) (Nizoral®), lopinavir (Kaletra®), lovastatin (Advicor®, Altoprev®, Mevacor®), mexiletine (Mexitil®), midazolam (when taken by mouth), milk thistle (Silybum marianum) or products containing milk thistle, nelfinavir (Viracept®), nevirapine (Viramune®, Viramune XR®), nicardipine (Cardene®), nifedipine (Adalat CC®, Afeditab CR®, Procardia®), nisoldipine (Sular®), oxcarbazepine (Trileptal®), phenobarbital (Luminal®), phenytoin (Dilantin®, Phenytek®), pitavastatin (Livalo®), posaconazole (when taken by mouth) (Noxafil®), pravastatin (Pravachol®), propafenone (Rythmol SR®), quinidine (Nuedexta®, Duraquin®, Quinaglute®), rifabutin (Mycobutin®), rifampin (Rifadin®, Rifamate®, Rifater®), rifapentine (Priftin®), ritonavir (Norvir®), rosuvastatin (Crestor®), saquinavir mesylate (Invirase®), sildenafil (Revatio®, Viagra®), simvastatin (Zocor®, Vytorin®, Simcor®), sirolimus (Rapamune®), St. John’s wort (Hypericum perforatum) or products containing St. John’s wort, tacrolimus (Prograf®), tadalafil (Adcirca®, Cialis®), telithromycin (Ketek®), tipranavir (Aptivus®), triazolam (when taken by mouth) (Halcion®), verapamil (Calan®, Covera-HS®, Isoptin®, Tarka®), voriconazole (when taken by mouth or when administered by injection) (Vfend®), warfarin (Coumadin®)
This is not a complete list of medicines that could interact with OLYSIO. Ask your healthcare provider or pharmacist if you are not sure if your medicine is one that is listed above.
Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.
What are the most common side effects of OLYSIO?
The most common side effects of OLYSIO when used in combination with peginterferon alfa and ribavirin include skin rash, itching, nausea.
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all of the possible side effects of OLYSIO. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
About Janssen Therapeutics
At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in hepatitis C, HIV and other infectious diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Headquartered in Titusville, New Jersey, Janssen Therapeutics, Division of Janssen Products, LP, is one of the Janssen Pharmaceutical Companies of Johnson & Johnson. Visit www.JanssenTherapeutics.com for more information and follow us on Twitter at @JanssenUS.
###
(This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Therapeutics, Inc. and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to, general industry conditions and competition; economic factors, such as interest rate and currency exchange rate fluctuations; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; challenges to patents; impact of business combinations; changes in behavior and spending patterns or financial distress of purchasers of health care products and services; changes to governmental laws and regulations and domestic and foreign health care reforms; trends toward health care cost containment; and increased scrutiny of the health care industry by government agencies. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 30, 2012. Copies of this Form 10-K, as well as subsequent filings, are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertake to update any forward-looking statements as a result of new information or future events or developments.)
NOTE: Janssen Therapeutics, Division of Janssen Products, LP, provides support to the Hepatitis C Association for initiatives benefitting individuals living with hepatitis C.
Media Contact: Craig Stoltz
Mobile: +1 (215) 325-3612
Media Contact: Daniel De Schryver
Mobile: +49 173 76 89 149
Investor Contact: Stan Panasewicz
Office: +1 (732) 524-2524
HCV Drug Olysio (simeprevir) - The New Kid On The Block
OLYSIO Website
Prescribing Information
Patient Information
Important Safety Information
Simeprevir and Sofosbuvir-The Next Wave of Hepatitis C Treatment
U.S. FDA approves J&J hepatitis C pill
Reuters) - U.S. regulators on Friday approved the use of Johnson & Johnson's Olysio, also known as simeprevir, as a treatment for chronic infection with the liver-destroying hepatitis C virus.
Olysio, a protease inhibitor that blocks a specific protein needed by the virus to replicate, is to be used in combination with interferon, given by injection, and ribavirin, another pill.
Hepatitis C affects about 3.2 million Americans, killing more than 15,000 each year, mostly from illnesses such as cirrhosis and liver cancer.
The often-undiagnosed virus is transmitted through contaminated blood. Infection rates have dropped since the early 1990s, due in part to the introduction of blood and organ screening. Still, many older adults remain at risk, according to the Centers for Disease Control and Prevention, which has called for baby boomers to be routinely tested for the virus.
Olysio is a member of the same class of drugs as Merck & Co's Victrelis and Vertex Pharmaceuticals' Incivek. The FDA approved both those drugs in 2011.
Olysio was shown in clinical trials to cure patients with a shorter duration of treatment.
Drugmakers have been racing to develop more effective, easier-to-tolerate antivirals to treat hepatitis C. Wall Street analysts have forecast annual sales of billions of dollars for new drugs that would allow doctors to skip use of interferon, which can cause severe flu-like side effects.
The FDA is slated to decide by December 8 on Gilead Sciences' application for sofosbuvir, a member of a different class known as nucleotide analogue inhibitors, or "nukes," designed to block a different enzyme the virus needs to copy itself.
European regulators on Friday recommended approval of the Gilead drug, under the brand name Sovaldi.
Other companies working to develop new hepatitis C drugs include AbbVie and Bristol-Myers Squibb.
(Reporting By Deena Beasley)
Press Release
OLYSIO™ (simeprevir) Receives FDA Approval for Combination Treatment of Chronic Hepatitis C
OLYSIOTM is the first once-daily protease inhibitor approved for the treatment of chronic hepatitis C in a combination antiviral regimen for adults with compensated liver disease
TITUSVILLE, N.J. (November 22, 2013) – Janssen Therapeutics, Division of Janssen Products, LP (Janssen), announced today the U.S. Food and Drug Administration (FDA) has approved OLYSIOTM (simeprevir), an NS3/4A protease inhibitor, for the treatment of chronic hepatitis C infection as part of an antiviral treatment regimen in combination with pegylated interferon and ribavirin in genotype 1 infected adults with compensated liver disease, including cirrhosis. OLYSIOTM may benefit patients with chronic hepatitis C, including those who are treatment naïve or who have failed prior interferon-based therapy.
Chronic hepatitis C is a blood-borne infectious disease of the liver that affects approximately 3.2 million people in the United States.
OLYSIOTM works by blocking the viral protease enzyme that enables the hepatitis C virus (HCV) to replicate in host cells. The goal of treatment for chronic hepatitis C is cure, also known as sustained virologic response (SVR), which is defined as undetectable levels of HCV in the patients’ blood 12 to 24 weeks after the end of treatment. For treatment-naïve and prior-relapser patients, a fixed treatment regimen of 12 weeks of OLYSIOTM combined with 24 weeks of pegylated interferon and ribavirin is recommended. For prior partial- and null-responder patients, a treatment regimen of 12 weeks of OLYSIOTM combined with 48 weeks of pegylated interferon and ribavirin is recommended.
“Given the complexity of the condition, OLYSIOTM was studied in a number of different patient populations, including individuals who have relapsed or failed to respond to previous treatments,” said Douglas Dieterich, M.D., Professor of Medicine in the Division of Liver Diseases, Mount Sinai School of Medicine, and OLYSIOTM clinical trial investigator. “The FDA approval of OLYSIOTM is an important milestone for people living with chronic hepatitis C as it means that patients have a new treatment option with the potential to cure this challenging disease.”
OLYSIOTM is a prescription medicine used with other antiviral medicines, pegylated interferon and ribavirin, to treat genotype 1 chronic hepatitis C in adults with stable liver problems. OLYSIOTM must not be taken alone. The efficacy of OLYSIOTM in combination with peginterferon and ribavirin is greatly decreased in patients who have genotype 1a Q80K. Please talk to your doctor about testing for genotype 1a Q80K and using a different therapy when genotype 1a Q80K is present. It is not known if OLYSIOTM is safe and effective in children under 18 years of age.
The New Drug Application (NDA) filed by Janssen Research & Development, LLC, for OLYSIOTM was based in part on efficacy and safety results from three pivotal Phase 3 studies – QUEST-1 and QUEST-2 in treatment-naïve patients and PROMISE in patients who have relapsed after prior interferon-based treatment – as well as data from the Phase 2b ASPIRE study in prior non-responder patients. Each of the studies evaluated OLYSIOTM dosed once daily in combination with pegylated interferon and ribavirin versus treatment with placebo plus pegylated interferon and ribavirin.
Results from a pooled analysis of QUEST-1 and QUEST-2 demonstrated that 80 percent of treatment-naïve patients in the group receiving OLYSIOTM achieved sustained virologic response 12 weeks after the end of treatment (SVR12), compared with 50 percent of patients in the placebo groups. In PROMISE, 79 percent of prior-relapser patients in the simeprevir group of the study achieved SVR12 compared with 37 percent of patients in the placebo group. Results from ASPIRE demonstrated that use of OLYSIOTM led to sustained virologic response 24 weeks after the end of treatment (SVR24) in 65 percent of prior partial-responder patients and 53 percent of prior-null responder patients compared with 9 percent and 19 percent of prior partial- and null-responder patients in the placebo groups, respectively.
In the QUEST-1 and QUEST-2 studies, among genotype 1a treatment-naïve patients receiving OLYSIOTM who had the Q80K polymorphism (a naturally occurring variation in the HCV NS3/4A protease enzyme), 58 percent achieved SVR12 versus 84 percent of patients without the Q80K polymorphism. In the placebo arm, 52 percent of patients with the Q80K polymorphism achieved SVR12. In the PROMISE study, among prior-relapser patients with the Q80K polymorphism who received OLYSIOTM, 47 percent achieved SVR12 versus 78 percent of patients without the polymorphism. In the placebo arm, 30 percent of patients with the Q80K polymorphism achieved SVR12.
“As an advocate working with the hepatitis C community, I’m pleased to know that Janssen has been working to make sure OLYSIOTM will be reasonably priced and available to the patients who need it,” said Sue Simon, President of the Hepatitis C Association. “It is notable that in addition to introducing a new treatment option for patients, Janssen is establishing comprehensive programs to support and assist patients in their treatment journey.”
Janssen has launched OLYSIOTM Support, a comprehensive support program designed in partnership with the HCV community to assist in the hepatitis C treatment journey so that patients and caregivers – and their healthcare providers – can focus on treatment. To register for OLYSIOTM Support or for additional information, please visit OLYSIO.com.
About OLYSIOTM (simeprevir)
OLYSIOTM (simeprevir) is an NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB and indicated in the U.S. for the treatment chronic hepatitis C infection in combination with pegylated interferon and ribavirin in HCV genotype 1 infected subjects with compensated liver disease, including cirrhosis.
Janssen is responsible for the global clinical development of OLYSIOTM and has exclusive, worldwide marketing rights, except in the Nordic countries. Medivir AB will retain marketing rights for OLYSIOTM in these countries under the marketing authorization held by Janssen-Cilag International NV. The treatment was approved in September 2013 in Japan under the trade name SOVRIADTM and in November 2013 in Canada under the trade name GALEXOSTM for the treatment of genotype 1 hepatitis C. A Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) in April 2013 by Janssen-Cilag International NV seeking approval of OLYSIOTM for the treatment of genotype 1 or genotype 4 chronic hepatitis C. To date, more than 3,700 patients have been treated with OLYSIOTM in clinical trials.
For additional information about OLYSIOTM, please visit www.OLYSIO.com
Important Safety Information
What is OLYSIO?
• OLYSIOTM (simeprevir) is a prescription medicine used with other antiviral medicines, peginterferon alfa and ribavirin, to treat genotype 1 chronic (lasting a long time) hepatitis C in adults with stable liver problems.
• OLYSIO must not be taken alone. The efficacy of OLYSIO in combination with peginterferon and ribavirin is greatly decreased in patients who have genotype 1a Q80K. Please talk to your doctor about testing for genotype 1a Q80K and using a different therapy when genotype 1a Q80K is present.
It is not known if OLYSIO is safe and effective in children under 18 years of age.
Important Safety Information
What is the most important information I should know and who should not take OLYSIO?
OLYSIO, in combination with peginterferon alfa and ribavirin may cause birth defects or death of your unborn baby. If you are pregnant or your sexual partner is pregnant, or plans to become pregnant, do not take these medicines. You or your sexual partner should not become pregnant while taking OLYSIO with peginterferon alfa and ribavirin and for 6 months after treatment is over.
Females and males must use two effective forms of birth control during treatment and for 6 months after treatment with OLYSIO, peginterferon alfa, and ribavirin combination therapy. Talk to your healthcare provider about forms of birth control that may be used during this time.
Females must have a pregnancy test before starting treatment with OLYSIO, peginterferon alfa, and ribavirin combination therapy, every month while being treated, and every month for 6 months after your treatment with OLYSIO, peginterferon alfa, and ribavirin combination therapy is over.
If you or your female sexual partner becomes pregnant while taking OLYSIO, peginterferon alfa, and ribavirin combination therapy or within 6 months after you stop taking these medicines, tell your healthcare provider right away. You or your healthcare provider should contact the Ribavirin Pregnancy Registry by calling 1-800-593-2214. The Ribavirin Pregnancy Registry collects information about what happens to mothers and their babies if the mother takes ribavirin while she is pregnant.
OLYSIO in combination with peginterferon alfa and ribavirin may cause rashes and skin reactions to sunlight. These rashes and skin reactions to sunlight can be severe and you may need to be treated in a hospital. Rashes and skin reactions to sunlight are most common during the first 4 weeks of treatment, but can happen at any time during treatment with OLYSIO, peginterferon alfa, and ribavirin combination therapy.
Use sunscreen, and wear a hat, sunglasses, and protective clothing when you will be exposed to sunlight during treatment with OLYSIO.
Limit sunlight exposure during treatment with OLYSIO
Avoid use of tanning beds, sunlamps, or other types of light therapy during treatment with OLYSIO.
Call your healthcare provider right away if you get any of the following symptoms:
burning, redness, swelling or blisters on your skin
mouth sores or ulcers red or inflamed eyes, like “pink eye” (conjunctivitis)
Do not take OLYSIO alone. OLYSIO should be used together with peginterferon alfa and ribavirin to treat chronic hepatitis C infection.
What should I tell my healthcare provider before taking OLYSIO?
Before taking OLYSIO, tell your healthcare provider if you:
have liver problems other than hepatitis C virus infection
have taken the medicines telaprevir (Incivek®) or boceprevir (Victrelis®)
had a liver transplant
are receiving phototherapy
have any other medical condition
are of East Asian descent
are breastfeeding. It is not known if OLYSIO passes into your breast milk. You and your healthcare provider should decide if you will take OLYSIO or breastfeed. You should not do both.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
OLYSIO and other medicines may affect each other. This can cause you to have too much or not enough OLYSIO or other medicines in your body, which may affect the way OLYSIO or your other medicines work, or may cause side effects. Do not start taking a new medicine without telling your healthcare provider or pharmacist.
Especially tell your healthcare provider if you take any of the following medicines: amiodarone (Cordarone®, Pacerone®), amlodipine (Norvasc®), atazanavir (Reyataz®), atorvastatin (Lipitor®, Caduet®), carbamazepine (Carbatrol®, Epitol®, Equetro®, Tegretol®), cisapride (Propulsid®, Propulsid Quicksolv®), clarithromycin (Biaxin®, Prevpac®), cobicistat-containing medicine: (Stribild®), cyclosporine (Gengraf®, Neoral®, Sandimmune®), darunavir (Prezista®), delavirdine mesylate (Rescriptor®), dexamethasone (when administered by injection or when taken by mouth), digoxin (Lanoxin®), diltiazem (Cardizem®, Dilacor XR®, Tiazac®), disopyramide (Norpace®), efavirenz (Sustiva®, Atripla®), erythromycin (E.E.S.®, Eryc®, Ery-Tab®, Erythrocin®, Erythrocin Stearate®), etravirine (Intelence®), felodipine (Plendil®), flecainide (Tambocor®), fluconazole (when taken by mouth or when administered by injection) (Diflucan®), fosamprenavir (Lexiva®), indinavir (Crixivan®), itraconazole (when taken by mouth) (Sporanox®, Onmel®), ketoconazole (when taken by mouth) (Nizoral®), lopinavir (Kaletra®), lovastatin (Advicor®, Altoprev®, Mevacor®), mexiletine (Mexitil®), midazolam (when taken by mouth), milk thistle (Silybum marianum) or products containing milk thistle, nelfinavir (Viracept®), nevirapine (Viramune®, Viramune XR®), nicardipine (Cardene®), nifedipine (Adalat CC®, Afeditab CR®, Procardia®), nisoldipine (Sular®), oxcarbazepine (Trileptal®), phenobarbital (Luminal®), phenytoin (Dilantin®, Phenytek®), pitavastatin (Livalo®), posaconazole (when taken by mouth) (Noxafil®), pravastatin (Pravachol®), propafenone (Rythmol SR®), quinidine (Nuedexta®, Duraquin®, Quinaglute®), rifabutin (Mycobutin®), rifampin (Rifadin®, Rifamate®, Rifater®), rifapentine (Priftin®), ritonavir (Norvir®), rosuvastatin (Crestor®), saquinavir mesylate (Invirase®), sildenafil (Revatio®, Viagra®), simvastatin (Zocor®, Vytorin®, Simcor®), sirolimus (Rapamune®), St. John’s wort (Hypericum perforatum) or products containing St. John’s wort, tacrolimus (Prograf®), tadalafil (Adcirca®, Cialis®), telithromycin (Ketek®), tipranavir (Aptivus®), triazolam (when taken by mouth) (Halcion®), verapamil (Calan®, Covera-HS®, Isoptin®, Tarka®), voriconazole (when taken by mouth or when administered by injection) (Vfend®), warfarin (Coumadin®)
This is not a complete list of medicines that could interact with OLYSIO. Ask your healthcare provider or pharmacist if you are not sure if your medicine is one that is listed above.
Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.
What are the most common side effects of OLYSIO?
The most common side effects of OLYSIO when used in combination with peginterferon alfa and ribavirin include skin rash, itching, nausea.
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all of the possible side effects of OLYSIO. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
About Janssen Therapeutics
At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in hepatitis C, HIV and other infectious diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Headquartered in Titusville, New Jersey, Janssen Therapeutics, Division of Janssen Products, LP, is one of the Janssen Pharmaceutical Companies of Johnson & Johnson. Visit www.JanssenTherapeutics.com for more information and follow us on Twitter at @JanssenUS.
###
(This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Therapeutics, Inc. and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to, general industry conditions and competition; economic factors, such as interest rate and currency exchange rate fluctuations; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; challenges to patents; impact of business combinations; changes in behavior and spending patterns or financial distress of purchasers of health care products and services; changes to governmental laws and regulations and domestic and foreign health care reforms; trends toward health care cost containment; and increased scrutiny of the health care industry by government agencies. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 30, 2012. Copies of this Form 10-K, as well as subsequent filings, are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertake to update any forward-looking statements as a result of new information or future events or developments.)
NOTE: Janssen Therapeutics, Division of Janssen Products, LP, provides support to the Hepatitis C Association for initiatives benefitting individuals living with hepatitis C.
Media Contact: Craig Stoltz
Mobile: +1 (215) 325-3612
Media Contact: Daniel De Schryver
Mobile: +49 173 76 89 149
Investor Contact: Stan Panasewicz
Office: +1 (732) 524-2524