December Hepatitis C Newsletters
**Updated Dec 19 - Check out The American Liver Foundation newsletter; Liver Low Down and this months Hepatitis C News "Video Broadcast" - provided below.
Hello folks, welcome to this months edition of newsletters, brought to you by a small group of exceptional people devoted to bringing awareness, support and information to the HCV community.
As you all know by now, in the last few weeks two new oral drugs were approved by the U.S. Food and Drug Administration to treat hepatitis C, Merry Christmas to us!
The first drug was approved in November, Olysio (simeprevir) a protease inhibitor for people with HCV genotype 1 used in combination with interferon and ribavirin. The second drug is Solvadi (sofosbuvir) the first FDA approved polymerase inhibitor, used for genotypes 1 and 4, in combination with interferon and ribavirin. As for people with genotypes 2 and 3 Solvadi is used with ribavirin alone, making it the first interferon free combination!
We start out with a video from Joe Galati, M.D., covering some HCV basics, followed by information on future and current direct-acting antivirals including a quick summary of Gilead's clinical trial data and finally background information on this months HCV newsletters.
Holy Inhibitors
Moving
forward it may prove difficult for patients to decide on an ideal drug, even a motivated lay person will be overwhelmed as they muddle
through a sea of Direct-Acting Antiviral Agents (DAA's) including second-wave PIs, non-nucleoside inhibitors, and
for good measure, polymerase inhibitors combined with second generation
protease inhibitors, holy inhibitors, I feel a song coming on;
You put the lime in the coconut and drink it all up
You put the lime in the coconut and call the doctor up
I said Doctor! Is there nothing I can take
I said Doctor! So much is at stake
So where do you start? Start by knowing the bottom line, or cure rates - of each new agent. This can be accomplished by reviewing news and updates on HCV advocate's blog; HCV pipeline.
Another great place to find early clinical trial data is by starting with HCV Advocate's index of newsletters, open up the newsletters, check out a column called "Snapshots" written by Lucinda K. Porter, write down the bottom line, editorial comments, results and finally the conclusion of each drug scrutinized. This month in the December newsletter its all about the AASLD, with a focus on breakthough therapies and a snapshot of abstracts presented at this years meeting - priceless.
You put the lime in the coconut and drink it all up
You put the lime in the coconut and call the doctor up
I said Doctor! Is there nothing I can take
I said Doctor! So much is at stake
I said Doctor! Do you ever make mistakes?
Start With The Basics
So where do you start? Start by knowing the bottom line, or cure rates - of each new agent. This can be accomplished by reviewing news and updates on HCV advocate's blog; HCV pipeline.
Another great place to find early clinical trial data is by starting with HCV Advocate's index of newsletters, open up the newsletters, check out a column called "Snapshots" written by Lucinda K. Porter, write down the bottom line, editorial comments, results and finally the conclusion of each drug scrutinized. This month in the December newsletter its all about the AASLD, with a focus on breakthough therapies and a snapshot of abstracts presented at this years meeting - priceless.
Protease inhibitors
What Protease Inhibitors Are FDA Approved?
Johnson & Johnson's OLYSIO (Simeprevir), Merck's Victrelis and Incivek by Vertex are approved to use in HCV genotype 1 treatment-naïve and previously treated patients, all protease inhibitors are used in combination with peginterferon alfa and ribavirin.
Link
EASL - Revised clinical practice guidelines for management of hepatitis C
Link
EASL - Revised clinical practice guidelines for management of hepatitis C
Protease Inhibitors: The Next Generation
On November 22, the FDA approved OLYSIO (Simeprevir), the first, “second generation” direct acting antiviral approved for
the treatment of HCV genotype 1 patients used in combination with
peginterferon alfa and
ribavirin in adults with compensated liver disease, including cirrhosis,
who are treatment-naïve or who have failed previous interferon therapy
(pegylated or non‑pegylated) with ribavirin. OLYSIO (simeprevir) is also approved in Japan and Canada.
For more information check out; HCV Drug Olysio (simeprevir) - The New Kid On The Block
Simeprevir - Q80K polymorphism
OLYSIO improved tolerability, has a lower pill burden and appears to
be slightly more effective than the standard of care, curing 80 percent
of treatment-naïve patients, but there are some
drawbacks. Before starting simeprevir patients with HCV genotype 1a need
to be screened for a genetic mutation called Q80K polymorphism.
Alternative therapy should be considered for people with the mutation,
according to simeprevir prescribing information
Links
Healio; Screening available for HCV Q80K polymorphism, more on the mutation - here
How Do Protease Inhibitors Work?
NS3/NS4A
protease inhibitors (PIs) target specific hepatitis C
virus enzymes essential for HCV replication.
Excerpt from HH Haven, article written by Teri Gottlieb;
The hepatitis C virus uses its protease enzyme to cut, or cleave, long strands of virus into shorter pieces, so that they can be rearranged and reassembled to form new viruses.
The above mentioned protease inhibitors stop viral cleavage by binding to the protease enzyme so it cannot cut, similar to covering scissor blades with glue.
The process is demonstrated in the video, published online by Express Scripts in 2011 after the first direct-acting antivirals (DAAs) boceprevir and telaprevir received FDA approval.
Polymerase inhibitors -NS5B
Hepatitis C polymerase inhibitors are another promising DAA class.
How Do Polymerase Inhibitors Work?
The newly FDA approved direct-acting antiviral (DAA) agent sofosbuvir,
is a NS5B polymerase inhibitor that inhibits the HCV-specific NS5B
polymerase, an enzyme the virus needs to copy itself. The drug has a potent antiviral activity against all identified HCV
genotypes with a high barrier to resistance.
Sofosbuvir FDA Approved - Polymerase Inhibitor
On December 6, the Food and Drug Administration approved Gilead's Sovaldi (sofosbuvir), an oral nucleotide analog inhibitor. Sofosbuvir will help treat people with advanced cirrhosis, as well as those awaiting liver transplant.
Tell Me You Didn't Just Say That
According to Gilead, Sovaldi will cost $84,000 for the 12 weeks of treatment and $168,000 for 24-weeks of treatment.
Low Income Countries
Today three percent of the world’s population is living with hepatitis C. With an estimated 185 million people infected worldwide, activist say the high price of these new drugs will make access impossible for people living in low and middle income countries.
Dec 9 - Fair Pricing Coalition Condemns Gilead Sciences on the High Price of New Hepatitis C Drug Sovaldi™, and Urges Rapid and Wide Dissemination of Support Program Details for Uninsured and Underinsured People Living with Hepatitis C
Excerpt: Activists pounce on $1,000-a-day price for Gilead's hep C wonder drug, Sovaldi
Dr. Jennifer Cohn, medical director of the Doctors Without Borders access-to-medicines campaign. The international healthcare organization is already pushing Gilead to sell Sovaldi on the cheap--$500, including diagnostics--when it's launched in developing countries. Already, the legal activist group Initiative for Medicines, Access & Knowledge has filed an opposition to patent protection for Sovaldi in India, aiming to pre-empt Gilead's pricing power.
December 11 - Why Talk Of A Hepatitis C Price War Should Act As A Warning To The Pharma Industry-At-Large
Why Talk Of A Hepatitis C Price War Should Act As A Warning To The Pharma Industry-At-Large Simon King, Contributor
Bloomberg Bloomberg reporter Drew Armstrong may have broken one of the most important pharmaceutical news stories of the year on Tuesday when he revealed that a leading US pharmacy benefits manager (PBM) is to take an aggressive stance towards the pricing of new hepatitis C therapies.
The crux of the story is that Express Scripts ESRX -0.58% will not view the convenience of Gilead Sciences' GILD -2.11% proposed single-tablet, fixed-dose combination treatment – due to be approved in late 2014/early 2015 – as an adequate justification for higher pricing versus less convenient therapies (i.e. more tablets) that deliverer a similar level of efficacy.
Gilead also announced pricing for Sovaldi, and payers are happy to see that Gilead settled on a cost south of the rumored $100,000 mark. Still, there's little joy at insurers, given that its $84,000 bill for a course of treatment dwarfs the $15,000 to $20,000 a year they were paying a few years ago for Peg-interferon and ribavirin.
Sovaldi's stiff price tag is also a big jump from the $50,000-a-year price commanded by Johnson & Johnson's and Vertex's Incivek, and Merck's Victrelis. Both of those drugs were recently approved in 2011, and Incivek was the fastest drug ever to reach $1 billion in sales.
Balking at paying
The decision to price Sovaldi higher than Johnson & Johnson's recently approved Olysio, formerly known as simeprevir, was bound to result in push back.
The first shove came from Express Scripts . The company suggests that it's willing to substitute lower priced competitors, even if those therapies come with a more unfriendly dosing schedule.
For now, that may prove an empty threat.
No other treatment, including Johnson's Olysio, is as effective across as large a patient pool as Sovaldi. Olysio, despite a solid showing in trials, struggled when treating patients with the Q80K polymorphism, which occurs in 50% of patients with hepatitis C, genotype 1a -- the most commonly occurring genotype in the United States.
That means Express Scripts has to hope AbbVie , with an up-and-coming multi-drug oral cocktail, will be willing to deal. So far, AbbVie's cocktail has enjoyed impressive results, including a 96% cure rate after 12 weeks in its most recent phase 3 trial.
Alternately, insurers could look to Bristol-Myers's daclatisvir, which is seeking approval in Japan as the first all-oral, interferon- and ribavirin-free treatment for the disease.
Foolishly creative math
The argument over pricing isn't a new debate for next-generation therapies. That means Express Scripts may be all bark and no bite. After all, hoping that AbbVie or Bristol-Myers will cut a deal to charge pharmacies less may prove a long shot, given that each has invested big money ushering its compound through clinical trials.
That's not to say there big buyers and big pharma can't strike deals behind closed doors. However, Gilead and Johnson's drugs, while more expensive, are also significantly better than predecessors. They cut the treatment time in half, with better outcomes. That suggests doctors and patients will embrace Sovaldi regardless of cost.
The article Gilead's Sofosbuvir Gets New Name, Price, Headaches originally appeared on Fool.com.
Interferon Free - For Genotype 2 and 3
Interferon and Ribavirin For Genotype 1 and 4
Sovaldi is approved in HCV genotypes 1 and 4, treatment-naïve adults in combination with PEG-IFN and ribavirin and the first approved interferon-free treatment regimen for people with HCV genotypes 2 and 3. Overall cure rates are at 80%, response rates and treatment duration varies, depending on genotype, viral and host factors.
| Treatment | Duration | |
| Patients with genotype 1 or 4 CHC | SOVALDI + peginterferon alfaa + ribavirinb | 12 weeks |
| Patients with genotype 2 CHC | SOVALDI + ribavirinb | 12 weeks |
| Patients with genotype 3 CHC | SOVALDI + ribavirinb | 24 weeks |
Interferon Free For Genotype 1
For Patients That Are Interferon Ineligible
Patients with Hepatocellular Carcinoma Who Are Waiting For A Liver Transplant
Sovaldi in combination with ribavirin for 24 weeks can be considered for CHC patients with genotype 1 infection who are interferon ineligible. Additionally, Sovaldi should be used in combination with ribavirin for treatment of CHC patients with hepatocellular carcinoma awaiting liver transplantation for up to 48 weeks or until liver transplantation to prevent post-transplant HCV infection. Treatment regimen, duration and response to Sovaldi are dependent on viral genotype and patient population, and associated baseline factors. Monotherapy is not recommended.
Patients with Hepatocellular Carcinoma Who Are Waiting For A Liver Transplant
Sovaldi in combination with ribavirin for 24 weeks can be considered for CHC patients with genotype 1 infection who are interferon ineligible. Additionally, Sovaldi should be used in combination with ribavirin for treatment of CHC patients with hepatocellular carcinoma awaiting liver transplantation for up to 48 weeks or until liver transplantation to prevent post-transplant HCV infection. Treatment regimen, duration and response to Sovaldi are dependent on viral genotype and patient population, and associated baseline factors. Monotherapy is not recommended.
Physician Views: FDA throws up surprise labelling for Gilead Sciences' hepatitis C treatment Sovaldi – will it boost first year uptake?
Confirmed late on Friday, FDA approval of Gilead Sciences' hepatitis C therapy Sovaldi (sofosbuvir) has been highly anticipated.
Nevertheless, the company managed to spring a surprise on both investors and rivals by securing labelling for Sovaldi as an all-oral therapy – in combination with ribavirin – for the large genotype 1 patient population (estimated 75 percent of US patient pool), when dosed over 24 weeks among patients who are deemed to be ‘ineligible’ to interferon.
Continue reading....
Sovaldi’s FDA approval is supported primarily by data from the following four Phase 3 studies.
----Overall SVR12 Results----
SVR 12 results from four Phase 3 clinical trials (NEUTRINO, FISSION, POSITRON and FUSION)
SVR 12 results from four Phase 3 clinical trials (NEUTRINO, FISSION, POSITRON and FUSION)
For detailed information please see Sovaldi (sofosbuvir) - Summary of the basis of approval and highlights from prescribing information and download the FDA review package for sofosbuvir
Study - National Institutes of Health
Real World Response Rate - Sofosbuvir/Ribavirin Without Interferon - Genotype 1 - Liver Fibrosis
In a small government study, people who are often not included in clinical trials represented a real world response rate. The study using a 24-week regimen of Sofosbuvir and weight-based or low-dose ribavirin without interferon, investigated genotype 1 subjects with all stages of liver fibrosis, the study was published in the August issue; Journal of the American Medical Association. Of the 60 patients in the trial, SVR24 results were 48 percent to 68 percent, depending on the drug dose.
Sofosbuvir as most of you know, is being tested with some of Gilead's other drugs, the combinations are projected to be highly effective, surpassing what is out there now, in particular the combination using sofosbuvir with ledipasvir. A summary of Gilead's studies with SVR12 results and major third wave anti HCV DAA agents making their way to FDA approval are listed below:
Gilead Is The Gift That Keeps On Giving
ELECTRON - Sofosbuvir and Ledipasvir Plus Either Ribavirin or GS-9669 For 12 Weeks -
Genotype 1
Genotype 1
In the ELECTRON trial genotype 1 treatment-naive and prior nonresponder patients were treated with sofosbuvir and ledipasvir plus either ribavirin or GS-9669 for 12weeks.
Excerpt; In ELECTRON trial, 100% of hard-to-treat patients cured with sofosbuvir/ledipasvir plus ribavirin or GS-9669
Interferon-free regimens of sofosbuvir and ledipasvir plus either ribavirin or GS-9669 taken for 12 weeks produced sustained response in 100% of treatment-experienced people with genotype 1 chronic hepatitis C virus (HCV) with advanced liver fibrosis or cirrhosis.
A related analysis of previously untreated people without cirrhosis found that reducing treatment duration to six weeks led to relapses.
Gilead Science's phase 2 ELECTRON trial programme has tested the nucleotide HCV polymerase inhibitor sofosbuvir (formerly GS-7977) in various all-oral regimens for increasingly difficult-to-treat patient populations.
The 12-week dual regimen of sofosbuvir plus ribavirin cures most people with easier-to-treat HCV genotypes 2 or 3, but the dual regimen was not adequate, however, for prior non-responders with genotype 1.
Researchers then tried adding the HCV NS5A inhibitor ledipasvir (GS-5885), finding that the triple regimen taken for 12 weeks produced a sustained virological response rate at 12 weeks post-treatment (SVR12) of 100% for both treatment-naive patients and prior non-responders without cirrhosis.
Phase 2 Trial LONESTAR - One Pill Two Drugs - Genotype 1- First trial to evaluate sofosbuvir and Ledipasvir for only eight weeks of treatment.
The company's LONESTAR study enrolled 100 genotype 1 patients to evaluate a once daily fixed-dose "combination tablet" containing sofosbuvir and ledipasvir (GS-5885) with and without ribavirin.
60 patients had never received treatment, 40 patients had been treated unsuccessfully using existing drugs. Of patients in the latter group, just over half (22 patients or 55%) had cirrhosis.
Patients took the combination pill for either 8 weeks or 12 weeks, and some patients in the study also received ribavirin as part of their regimen. Participants were stratified into different groups according to whether they had previously received treatment for hepatitis C, their length of treatment, and whether they received the new combination pill alongside ribavirin or not.
Results
At 12 weeks following the completion of therapy, nearly all (97 or 97%) of the patients in the study had achieved a sustained virological response (SVR) – essentially a functional cure for hepatitis C, where the virus is eliminated, and prevented from replicating.
Side Effects
Just under half of the patients in the study experienced at least one adverse event, with the highest rates observed in the groups of patients who were receiving ribavirin as part of their treatment regimen. No patient in any group discontinued treatment because of an adverse event.
Source
Success Story Sofosbuvir, Ledipasvir and Ribavirin
Lucinda K. Porter, RN, a health educator and author, (our own advocate) treated for 12 weeks with the blockbuster combination pill and ribavirin. Mosey on over to read her story, check out; "Hepatitis C Treatment One Step at a Time", a must read before starting treatment, and learn more about HCV, here. Be honest, have you ever used the word mosey in a conversation?
ION-1, ION-2, and ION-3
Update - Dec 18 2013
Gilead Announces SVR12 Rates From Three Phase 3 Studies Evaluating a Once-Daily Fixed-Dose Combination of Sofosbuvir and Ledipasvir for Genotype 1 Hepatitis C Patien
Press Release:
Gilead's Sofosbuvir and Ledipasvir Outstanding Late-stage Hepatitis C Data
ION-1 and ION-2
Ongoing Phase 3 studies are examining all-oral HCV therapy with sofosbuvir and ledipasvir. ION-1 and ION-2 are testing 12- and 24-week courses of the fixed-dose combination with and without RBV among treatment-naïve and treatment-experienced genotype 1 HCV patients, including those with compensated cirrhosis. Based on the results of the LONESTAR trial, Gilead has amended ION-2 to shorten the duration of therapy in one of the two fixed-dose combination arms without RBV from 24 to 12 weeks.
ION-3 Trial
Connect With Patients Participating In - LONESTAR, ELECTRON, ION-1, ION-2, and ION-3
Love It Links
MedHelp is an established forum made up of people living with HCV. Questions, and discussions are based on HCV and treatment. An interesting thread with over 120 comments referring to Gilead's LONESTAR, ELECTRON, ION-1, ION-2, ION-3 trials, including participant statistics ranging from August - November 2013, is available here.
Gilead’s Sovaldi™ (Sofosbuvir)
U.S. Patient Assistance Program Gilead is committed to ensuring that people with hepatitis C can access Sovaldi and has launched Support Path™ (www.MySupportPath.com) to provide assistance to patients who are uninsured, underinsured or who need financial assistance to pay for the medicine
**Clinical Trials which are now enrolling can be found online @ HCV Advocate - Gilead
WebMD added a FAQ list for both newly approved protease inhibitor Olysio (simeprevir) and polymerase inhibitor Solvadi (sofosbuvir)
Play Nice, Just Play To Win
Despite their limitations, protease inhibitors have high antiviral efficacy and will play an important role in future therapies. Newer protease inhibitors in development: asunaprevir, danoprevir, vaniprevir, MK-5172, and faldaprevir (BI-201335) are expected to have improved tolerance and safety profiles and will likely be used in combination with pegylated interferon and ribavirin or in newer DAA combination regimens in the future.
Excerpt; Treatment of chronic hepatitis C virus infection in the near future, found in November-December issue of Annals Of Hepatology.
Protease Inhibitors End In The Suffix “previr”, NS5A Inhibitors End In “asvir” and so on...
Interestingly, the ending of the denomination of these new agents usually indicates the target of the molecule on the HCV molecule, so that NS3/4A pro-tease inhibitors end in the suffix “previr”, NS5A inhibitors end in “asvir” and NS5B polymerase inhibitors end in “buvir”
The main companies and drug combinations that make the bulk of the third wave anti HCV DAA agents are listed below:
1. BOHERINGER-INGELHEIM
• The phase 3 trial STARTVerso-124 explored the combination of faldaprevir (NS3/4A protease inhibitor) at a dose of 120 mg and 240mg, taken once daily, plus PEG-IFNα/RBV for 24 to 48 weeks according to response guided criteria vs. PEG-IFNa/RBV for 48 weeks ina group of treatment naïve chronic HCV geno-type-1 patients, with an SVR of 79% (faldaprevir 120 mg) vs. 80% (faldaprevir 240 mg) vs. 52% (PEG-IFNα/RBV), respectively.
Importantly, 88% of the patients in the faldaprevir120 mg arm were able to achieve response guided criteria and shortened therapy to24 weeks. Safety profile was good However,there were little more than 5% cirrhotics included in this trial .
Hepatitis C: Boehringer Ingelheim's faldaprevir granted accelerated assessment from European Medicines Agency - press release.
.
• Faldaprevir plus deleobuvir (NS5B non nucleoside polymerase inhibitor) with and without RBV were tested in a randomized,open-label, Phase 2b trial.25 SVR rates ranged from 56 to 85% among patients with genotype1b infection vs. 11 to 47% among patients with genotype 1a infection and 58 to 84%among patients with IL28B CC vs. 33 to 64%with non-CC genotypes. Rash, photosensitivity, nausea, vomiting, and diarrhea were the most common adverse events.
2. ABBVIE
• The AVIATOR26 is a Phase 2b study designed to assess the safety and efficacy of ABT-450/r (dosed 100/100 to 200/100 mg once daily), ABT-267 (25 mg once daily), ABT-333 (400 mg twice daily) and ribavirin in non-cirrhotic treatment-naive patients and prior PEG-IFNα/RBV null responders with HCV genotype
1. Duration varied from 8, 12 or 24 weeks of treatment.The 12-week triple-DAA regimen with RBV achieved SVR-12 in 99% of treatment naive patients and 96% of SVR-24 in intent to treat analysis. Furthermore, 93% of prior null responders achieved SVR-12 and SVR-24. 3.
Dec 10 - AbbVie Demonstrates 96 percent SVR(12) Phase III Treatment-Experienced Patients with Geno 1 Hepatitis C
GILEAD
• The ELECTRON 27 study tested Sofosbuvir (NS5B nucleotide polymerase inhibitor) plus ledipasvir (NS5A inhibitor) plus RBV for 12weeks in a small group of HCV genotype 1treatment-naive patients (n = 25) and prior null responders (n = 9), without cirrhosis. All patients (100%) achieved SVR-12. 4.
BRISTOL-MYERS SQUIBB
• The COMMAND-128 was a randomized, double-blinded, placebo-controlled, Phase 2b clinical study of daclatasvir (NS5A inhibitor) plus PEG-IFNα/RBV for 24 to 48 weeks in treatment naïve chronic HCV genotype-1 (n = 365)or 4 (n = 30) infected patients. Each treatment group included 5-10% compensated cirrhotic patients. The SVR-12 was 65%for genotype 1 and reached 100% in one of the genotype 4 arms. SVR was better among genotype 1b compared to 1a (87% vs. 58%,respectively). Tolerability was good overall.
• The COMMAND-229 study explored the combination of daclatasvir (NS5A inhibitor) plus PEG-IFNα/RBV for 12 to 16 weeks vs. PEG-IFNα/RBV for 24 weeks in 151 treatment naïve chronic HCV genotype-2 or 3 patients.SVR-12 among genotype-2 patients was 88%,83% and 63% in the daclatasvir 12 weeks, 16 weeks and controls, respectively. SVR-12among genotype-3 patients was 69, 70 and59% in the daclatasvir 12 weeks, 16 weeks and controls, respectively. Side-effects were those commonly experienced with PEG-IFNα/RBV alone
• The combination of daclatasvir (NS5A in-hibitor) plus asunaprevir (NS3/4A protease inhibitor) plus BMS-791325 (non-nucleosideNS5B inhibitor) was studied in a randomized,open-label, Phase 2 trial in treatment naïve patients with HCV Genotype 1 infection and without cirrhosis.30 Of the 66 enrolled patients, 74% had genotype 1a infection and 30% had IL-28B CC genotype. The SVR-12rate ranged from 88 to 94%, with no significant difference between 12 and 24 weeks.Tolerability was good overall. 5.
BRISTOL-MYERS SQUIBB PLUS GILEAD
• Daclatasvir (NS5A inhibitor) plus sofosbuvir(NS5B nucleotide polymerase inhibitor) for 12 to 24 weeks has 100% rate of SVR in treatment naïve chronic HCV genotype-1, 2 and 3patients.31In another study, 32 a total of 41 HCV genotype1 patients with previous failure to telaprevir and boceprevir were randomly assigned to daclatasvir 60 mg once daily plus sofosbuvir 400 mg once daily with or without ribavirin for a total of 24 weeks. Patients with cirrhosis were excluded. The majority had HCV genotype1a and 98% of patients had a non-CC IL-28Bgenotype. SVR-12 was 100%.
Sept - Doctor granted FDA emergency approval to use sofosbuvir/daclatasvir for hepatitis C transplant patient
Posted on June 17, 2013 by Kristine Novak, PhD, Science Editor
In patients with chronic Hepatitis C virus (HCV) infection, a sustained viral response to treatment regimens 12 weeks after therapy (SVR12) is a good indicator that the response will be maintained until week 24 (SVR 24), based on an analysis of pooled clinical trial data published in the June issue of Gastroenterology. Therefore SVR12 can be used instead of SVR24 as a primary end point for registration trials.
A SVR24 (undetectable levels of HCV RNA in serum 24 weeks after completion of therapy) is considered to indicate successful treatment—most patients who achieve SVR24 maintain their serum-negative status and have reduced complications from liver disease and increased survival times. It is therefore the primary endpoint of HCV therapy trials for regulatory approval—efficacies of all HCV therapies approved by the US Food and Drug Administration have been based on the proportion of patients attaining SVR24. However, earlier time points could increase efficiency of drug development.
Jianmeng Chen et al. assessed data from 15 phase 2 and 3 trials, 3 pediatric studies, and 5 drug-development programs to determine the concordance between SVR24 and SVR12, and even SVR4. They analyzed data from groups of subjects who received various combinations and regimens with interferon, ribavirin, and direct-acting antiviral agents.
Of the 13,599 adult subjects in the database analyzed, 50.6% achieved SVR24 and 51.8% achieved SVR12. These appeared to be mostly the same patients—the positive predictive value of SVR12 for SVR24 was 98% and the negative predictive value was 99% among subjects with genotype 1 HCV infection. A similar level of concordance was observed in subjects with HCV genotype 2 or 3 infections, as well as in pediatric studies.
The positive predictive value of SVR4 for SVR24 was 91% and the negative predictive value was 98% in subjects with genotype 1 HCV infection. Chen et al. observed similar values regardless of subjects’ race, sex, treatment experience, genotype 1a vs 1b, or presence of cirrhosis.
Why is there such a high level of agreement between SVR12 and SVR24, and to a lesser extent SVR4 and SVR24? Chen et al. explained that 65% of subjects who relapsed had detectable viral load by week 4 after treatment and 95% had detectable viral load by week 12. So if the virus is going to reappear, in generally does so within 12 weeks after the treatment ends.
The authors conclude that individual patients should be followed for 24 weeks or longer after treatment to confirm their responses. But SVR12, which is currently used as supportive information for registration trial design, can also be appropriate for regulatory approval of treatment regimens.
Welcome, The Hepatitis C Mentor and Support Group (HCMSG) to our monthly index of newsletters. Ronni Marks, the founder and director of HCMSG, is an advocate for people living with hepatitis C, devoting his time, energy and experience by traveling across the country providing training necessary for running successful HCV support groups. Mr. Marks recently mentioned he just returned from Alaska, with this wave of new HCV agents his services are invaluable, a service which is free of charge and an important step to ensure patients understand treatment.
Marks was diagnosed with Hepatitis C in 1997, he founded HCMSG to bring awareness, support, and services for people living with Hepatitis C (including patients co-infected with other conditions such as HIV/AIDS and Hepatitis B), and patients in need of or living with liver transplants. He writes;
• Faldaprevir plus deleobuvir (NS5B non nucleoside polymerase inhibitor) with and without RBV were tested in a randomized,open-label, Phase 2b trial.25 SVR rates ranged from 56 to 85% among patients with genotype1b infection vs. 11 to 47% among patients with genotype 1a infection and 58 to 84%among patients with IL28B CC vs. 33 to 64%with non-CC genotypes. Rash, photosensitivity, nausea, vomiting, and diarrhea were the most common adverse events.
2. ABBVIE
• The AVIATOR26 is a Phase 2b study designed to assess the safety and efficacy of ABT-450/r (dosed 100/100 to 200/100 mg once daily), ABT-267 (25 mg once daily), ABT-333 (400 mg twice daily) and ribavirin in non-cirrhotic treatment-naive patients and prior PEG-IFNα/RBV null responders with HCV genotype
1. Duration varied from 8, 12 or 24 weeks of treatment.The 12-week triple-DAA regimen with RBV achieved SVR-12 in 99% of treatment naive patients and 96% of SVR-24 in intent to treat analysis. Furthermore, 93% of prior null responders achieved SVR-12 and SVR-24. 3.
Dec 10 - AbbVie Demonstrates 96 percent SVR(12) Phase III Treatment-Experienced Patients with Geno 1 Hepatitis C
GILEAD
• The ELECTRON 27 study tested Sofosbuvir (NS5B nucleotide polymerase inhibitor) plus ledipasvir (NS5A inhibitor) plus RBV for 12weeks in a small group of HCV genotype 1treatment-naive patients (n = 25) and prior null responders (n = 9), without cirrhosis. All patients (100%) achieved SVR-12. 4.
BRISTOL-MYERS SQUIBB
• The COMMAND-128 was a randomized, double-blinded, placebo-controlled, Phase 2b clinical study of daclatasvir (NS5A inhibitor) plus PEG-IFNα/RBV for 24 to 48 weeks in treatment naïve chronic HCV genotype-1 (n = 365)or 4 (n = 30) infected patients. Each treatment group included 5-10% compensated cirrhotic patients. The SVR-12 was 65%for genotype 1 and reached 100% in one of the genotype 4 arms. SVR was better among genotype 1b compared to 1a (87% vs. 58%,respectively). Tolerability was good overall.
• The COMMAND-229 study explored the combination of daclatasvir (NS5A inhibitor) plus PEG-IFNα/RBV for 12 to 16 weeks vs. PEG-IFNα/RBV for 24 weeks in 151 treatment naïve chronic HCV genotype-2 or 3 patients.SVR-12 among genotype-2 patients was 88%,83% and 63% in the daclatasvir 12 weeks, 16 weeks and controls, respectively. SVR-12among genotype-3 patients was 69, 70 and59% in the daclatasvir 12 weeks, 16 weeks and controls, respectively. Side-effects were those commonly experienced with PEG-IFNα/RBV alone
• The combination of daclatasvir (NS5A in-hibitor) plus asunaprevir (NS3/4A protease inhibitor) plus BMS-791325 (non-nucleosideNS5B inhibitor) was studied in a randomized,open-label, Phase 2 trial in treatment naïve patients with HCV Genotype 1 infection and without cirrhosis.30 Of the 66 enrolled patients, 74% had genotype 1a infection and 30% had IL-28B CC genotype. The SVR-12rate ranged from 88 to 94%, with no significant difference between 12 and 24 weeks.Tolerability was good overall. 5.
BRISTOL-MYERS SQUIBB PLUS GILEAD
• Daclatasvir (NS5A inhibitor) plus sofosbuvir(NS5B nucleotide polymerase inhibitor) for 12 to 24 weeks has 100% rate of SVR in treatment naïve chronic HCV genotype-1, 2 and 3patients.31In another study, 32 a total of 41 HCV genotype1 patients with previous failure to telaprevir and boceprevir were randomly assigned to daclatasvir 60 mg once daily plus sofosbuvir 400 mg once daily with or without ribavirin for a total of 24 weeks. Patients with cirrhosis were excluded. The majority had HCV genotype1a and 98% of patients had a non-CC IL-28Bgenotype. SVR-12 was 100%.
Sept - Doctor granted FDA emergency approval to use sofosbuvir/daclatasvir for hepatitis C transplant patient
SVR12, SVR24 Which One Is Better?
Posted on June 17, 2013 by Kristine Novak, PhD, Science Editor
In patients with chronic Hepatitis C virus (HCV) infection, a sustained viral response to treatment regimens 12 weeks after therapy (SVR12) is a good indicator that the response will be maintained until week 24 (SVR 24), based on an analysis of pooled clinical trial data published in the June issue of Gastroenterology. Therefore SVR12 can be used instead of SVR24 as a primary end point for registration trials.
A SVR24 (undetectable levels of HCV RNA in serum 24 weeks after completion of therapy) is considered to indicate successful treatment—most patients who achieve SVR24 maintain their serum-negative status and have reduced complications from liver disease and increased survival times. It is therefore the primary endpoint of HCV therapy trials for regulatory approval—efficacies of all HCV therapies approved by the US Food and Drug Administration have been based on the proportion of patients attaining SVR24. However, earlier time points could increase efficiency of drug development.
Jianmeng Chen et al. assessed data from 15 phase 2 and 3 trials, 3 pediatric studies, and 5 drug-development programs to determine the concordance between SVR24 and SVR12, and even SVR4. They analyzed data from groups of subjects who received various combinations and regimens with interferon, ribavirin, and direct-acting antiviral agents.
Of the 13,599 adult subjects in the database analyzed, 50.6% achieved SVR24 and 51.8% achieved SVR12. These appeared to be mostly the same patients—the positive predictive value of SVR12 for SVR24 was 98% and the negative predictive value was 99% among subjects with genotype 1 HCV infection. A similar level of concordance was observed in subjects with HCV genotype 2 or 3 infections, as well as in pediatric studies.
The positive predictive value of SVR4 for SVR24 was 91% and the negative predictive value was 98% in subjects with genotype 1 HCV infection. Chen et al. observed similar values regardless of subjects’ race, sex, treatment experience, genotype 1a vs 1b, or presence of cirrhosis.
Why is there such a high level of agreement between SVR12 and SVR24, and to a lesser extent SVR4 and SVR24? Chen et al. explained that 65% of subjects who relapsed had detectable viral load by week 4 after treatment and 95% had detectable viral load by week 12. So if the virus is going to reappear, in generally does so within 12 weeks after the treatment ends.
The authors conclude that individual patients should be followed for 24 weeks or longer after treatment to confirm their responses. But SVR12, which is currently used as supportive information for registration trial design, can also be appropriate for regulatory approval of treatment regimens.
December Hepatitis Newsletters
Marks was diagnosed with Hepatitis C in 1997, he founded HCMSG to bring awareness, support, and services for people living with Hepatitis C (including patients co-infected with other conditions such as HIV/AIDS and Hepatitis B), and patients in need of or living with liver transplants. He writes;
My hope is that this newsletter will be a form of support to those newly diagnosed, just dealing, making decisions, on treatment and even after treatment.
The Hepatitis C Mentor and Support Group (HCMSG) was founded to address the lack of awareness, support, and services for people living with Hepatitis C (including patients co-infected with other conditions such as HIV/AIDS and Hepatitis B), and patients in need of or living with liver transplants. To address these needs, we provide resources and services to foster the development and operation of successful support groups for Hepatitis C and co-infected patients. These services are provided to prospective and current support group facilitators FREE OF CHARGE. In the future, we will also provide one-on-one mentoring services to Hepatitis C and liver transplant patients.
In This Issue
NEWS WATCH FOR 2015
Direct acting antiviral (DAA) combination without interferon.
Hepatitis terminology
Must ask questions about medications
and more........
We welcome your suggestions on what you would like to see in upcoming issues and any stories you want to share.
HCV Advocate - A Nice Place To Spend Some Quality Time
So much is going on at the Peoples Website!
Grab a cup of coffee, tea, or some expensive bottled water; priced at around a 4,000% markup, as my father would say, and start reading the news.
The HCV Advocate newsletter is a valuable resource designed to provide the hepatitis C community with monthly updates on events, clinical research, and education
December Newsletter
In This Issue:
AASLD: Focus on "Breakthrough Therapies"
Alan Franciscus, Editor-in-Chief
HEALTHWISE: Liver Meeting 2013 Update
Lucinda K. Porter, RN
Snapshots: AASLD Special
Lucinda K. Porter, RN
HIV/HCV Coinfection at AASLD 2013
Liz Highleyman
Simeprevir (Olysio): FDA Approved!
Alan Franciscus, Editor-in-Chief
‘Guide’ to AASLD 2013
Click Here
A Guide to AASLD 2013: We are pleased to offer our first ‘Guide’ to AASLD 2013, containing a whole bunch of important information about hepatitis C and HIV/HCV coinfection. Included in the guide is all of our coverage from AASLD including that from the December 2013 HCV Advocate newsletter.
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New: GT4 Treatment: Sovaldi Triple Therapy
Click Here
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Check out our new fact sheets and the prescribing information for simeprevir (Olysio)
Olysio (Simeprevir) –Easy C.
Olysio (Simeprevir) –Easy C.
Olysio (Simeprevir) –Fact Sheet.
Olysio (Simeprevir) –Package Insert. HEPATITIS B
HBV Journal Review by Christine Kukka
In this month's column Chris reviews the following studies that will help you understand the complexities of hepatitis B, including
Studies Find Hepatitis B Virus Can Mutate and Infect Even Immunized People
Hepatitis B Patients Appear to Be At Risk of Other Diseases
Experts: Do Not Rush to Treat HBV-Infected Children
Primary Care Doctors Essential in Treating Immigrants at Risk of Liver Cancer
Relapse Rate Low in Those Who Respond Well to Entecavir
Only 64% of U.S. Health Care Providers Are Immunized Against Hepatitis B
Studies Reveal Important Information about Hepatitis B in Women
Hepatitis B Risk in African Immigrants and African-Americans Studied
We have updated all of the Easy B fact sheets in the Diagnostic Tools & Markers, and Transmission / Prevention series.
HCV Advocate News & Pipeline Blog!
Be sure to check out the latest clinical trial postings at the HCV Advocate News & Pipeline Blog. Just click on the links to the Drug Companies below the banner to see which drugs are in trials right now, where the trials are, and how to register for one.
Be sure to check out the latest clinical trial postings at the HCV Advocate News & Pipeline Blog. Just click on the links to the Drug Companies below the banner to see which drugs are in trials right now, where the trials are, and how to register for one.
Connect With HCV Advocate
HepCBC’s MONTHLY NEWSLETTER
The hepc.bull, has been “Canada’s hepatitis C journal” since the late 1990′s and has been published nonstop since 2001. The monthly newsletter contains the latest research results, government policy changes, activities and campaigns you can get involved in, articles by patients and caregivers, and a list of support groups plus other useful links.
ARTICLES IN THIS ISSUE:
Treatment: Loads of Useful "How To Prepare" Tips from a newly-cured patient
Clinical Trials: Reflections, Inspiration, and Sobering Advice from (another!) newly-cured patient
Powerful Drugs in the Pipeline: simeprevir (recently approved by Health Canada and going under trade name Galexos), sofosbuvir (currently undergoing CADTH review), faldaprevir, and ledipasvir
Holiday Letter
Invitation to Dec. 8th Benefit Concert in Victoria
Conferences, Medication Assistance, Compensation
HCV Support Groups in Canada
AND MORE!!
Stay Connected
Treatment: Loads of Useful "How To Prepare" Tips from a newly-cured patient
Clinical Trials: Reflections, Inspiration, and Sobering Advice from (another!) newly-cured patient
Powerful Drugs in the Pipeline: simeprevir (recently approved by Health Canada and going under trade name Galexos), sofosbuvir (currently undergoing CADTH review), faldaprevir, and ledipasvir
Holiday Letter
Invitation to Dec. 8th Benefit Concert in Victoria
Conferences, Medication Assistance, Compensation
HCV Support Groups in Canada
AND MORE!!
Stay Connected
NYC Viral Hepatitis Monthly E-Newsletter
NYC Hep C Task Force | NYC Hep B Coalition
2013 December NYC Hepatitis ABC Newsletter
Upcoming Events
Hepatitis Health Care Access Training.
December 10 (12:30 - 5 PM). Beth Israel, 10 Union Square East, 2nd Floor Auditorium. Organized by NYC Hep C Task Force, NYC Hep B Coalition, NYC Department of Health & Centers for Medicaid & Medicare Services. Covering: The Affordable Care Act in NYC & Hepatitis Special Issues, Health Insurance eligibility and enrollment instructions, covered services, pharmacy issues & health care access for the uninsurable.
Register
NYS Hep C Testing Law: Stakeholder Meeting
NYS Department of Health. December 16 (10 AM - Noon). 90 Church Street.
NYS Hep C Testing Law: Stakeholder Meeting
NYS Department of Health. December 16 (10 AM - Noon). 90 Church Street.
Convened as a strategic way to
collect information, input and comments about the implementation
of the new Hepatitis C Testing Law.
It is also an opportunity for providers to ask questions.
Register: hepatabc@health.state.ny.us.
of the new Hepatitis C Testing Law.
It is also an opportunity for providers to ask questions.
Register: hepatabc@health.state.ny.us.
and more.......
Join Us
GI
& Hepatology News is the official newspaper of the AGA Institute
and provides the gastroenterologist with timely and relevant news and
commentary about clinical developments and about the impact of
health-care policy. The newspaper is led by an internationally renowned
board of editors.
Today we have a newsletter update, GI & Hepatology News the official newspaper of the AGA Institute just published their montly newsletter.
December Issue
Today we have a newsletter update, GI & Hepatology News the official newspaper of the AGA Institute just published their montly newsletter.
December Issue
Stay connected
American Liver Foundation
Liver Lowdown is the monthly general interest e-newsletter of the American Liver Foundation.
In accordance with the Foundation’s mission, the e-newsletter is disseminated to provide information about the prevention, treatment and cure of liver disease, as well as the organization’s research and advocacy endeavors.
In accordance with the Foundation’s mission, the e-newsletter is disseminated to provide information about the prevention, treatment and cure of liver disease, as well as the organization’s research and advocacy endeavors.
Content includes updates about the Foundation’s educational and signature programs; an in-depth focus on specific types of liver disease, and profiles of liver patients’ and caregivers’ personal experiences
December Newsletter
FEATURE
Living With Hepatitis C: Importance of Taking Medications as Directed
Prescription drugs can provide important benefits to individuals living with hepatitis C, but taking these medications as prescribed can be difficult. Some individuals struggle with drug side effects and costs while others may forget to take medication on time or order refills. Fortunately there are steps that can help address these challenges and better manage this condition through medication.
READ MORE
HEPATITIS C UPDATE
American Liver Foundation Hails Promise of Cure Signaled by Approval of New Hepatitis C Treatments
The FDA has approved two new treatments for hepatitis C: Sovaldi, to be used in combination with other anti‐virals; and Olysio, the first once-daily protease inhibitor. Welcoming the approval of these breakthrough drugs, American Liver Foundation National Board Chair Tom Nealon said: "This is the beginning of a new, gentler, era in the treatment of hepatitis.”
READ MORE
LOOKING BACK AT 2013
The Year in Pictures
Here’s a sampling of pictures to illustrate how we promoted the need for liver disease awareness during 2013. One of the highlights: A photo showing members of our Run for Research Team symbolically completing the Boston Marathon nearly three weeks after the event was the site of a shocking bombing. Their message: “We are Boston Strong!”
READ MORE
CHECK YOUR SCORE: HOW MUCH DO YOU KNOW ABOUT YOUR LIVER?
For the festive season, when you get a moment to relax, find out how much you know about the liver. This multiple choice quiz poses intriguing questions such as: Where did the first successful liver transplant take place? And why would we ask a question where the answer could be Michael Jackson, Ray Charles, John Lennon or Frank Sinatra?
READ MORE
HEALTHY RECIPES FOR THE HOLIDAYS
Looking to cook up something healthy and out of the ordinary for the holidays? The American Liver Foundation has the answer! Two celebrated chefs, who are involved with our annual Flavors events, suggest these mouthwatering recipes: Chestnut Stuffing (Chef Beau MacMillan) and Soup of Red Bell Pepper (Chef Christopher Gross). Happy cooking…and eating!
READ MORE
ALF Website
1-800-GOLIVER (1-800-465-4837)
In addition, questions sent on e-mail to info@liverfoundation.org will be promptly answered.
**Check Back For December Newsletter
Stay Connected
Check Us Out On Twitter and Facebook
Visit HepatitisCNews.com, an online community for those living with hepatitis C
Spotlight Series
In the latest entry in our ‘Spotlight on…’ series we focus on American vocalist, Anthony Kiedis. Best known for his work as the lead singer of US rock group Red Hot Chili Peppers, he has sold over 80 million albums and collected 7 Grammy awards with the group.
In December - Your Stories
In a word, my appraisal of telaprevir treatment is tough! I am now on week 8 and in the thick of it. It is very different to previous combo treatments I have had, and in many respects is a whole new ball game. Telaprevir has its own side-effects and magnifies other ones that you might expect from standard interferon/ribavirin treatment.
Discrimination is a burden faced on a daily basis by those living with hep C.
Hep C is sometimes seen as a disease that does not affect ‘nice’ people, because it is associated with ‘deviant’ behavior. This is largely due to lack of education and understanding. Indeed, most people will not think twice about how they react to a person infected with the hepatitis C virus.
Whilst discrimination can be subtle or overt, direct or indirect, it can occur in all areas of our lives. All of us have the right not to be discriminated against.
Stay connected
Other Health Websites
December Updates
You’re one of a kind. It’s not just your eyes, smile, and personality. Your health, risk for disease, and the ways you respond to medicines are also unique. Medicines that work well for some people may not help you at all. They might even cause problems.
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ACP Internist provides news and information for internists about the practice of medicine and reports on the policies, products and activities of ACP
November/December Issue
ACP Internist
Current Issue
November/December Issue
ACP Internist
Current Issue
Q&A: Doctors have an online presence, even if they don’t know it yet
Editor’s Note
Helping patients navigate the Web is tricky, but worthwhile
By Jennifer Kearney-Strouse
This issue includes stories on patients using the Internet to diagnose themselves, on low back pain (one of the most common reasons for a clinical visit), and on managing a physician’s online reputation.
Patients increasingly checking ‘Dr. Google’
By Stacey Butterfield
As a family physician who has used an electronic medical record for 12 years, Gary Bevill, MD, sees himself as open to new technological advances. But the advent of Internet tools that allowed patients to enter their symptoms and receive possible diagnoses displeased him and many physicians.
“I like to think I’m semi-wired,” Dr. Bevill said. “But as a general rule, the early symptom checkers, I basically hated with a passion.”
The increasing tendency of patients to visit “Dr. Google”—35% of U.S. adults have gone online to try to identify a medical condition in themselves or someone else, according to a 2013 survey from Pew Research Center—raised several concerns.
“The classic physician concern is the patient will put in headache, and they’re going to get freaked out because brain tumor will come up, and we’re going to be inundated with people coming in with [imagined] brain tumors,” said Jason Maude, founder and CEO of Isabel Healthcare, a company that offers an online symptom checker for patients.
Wishing you all a safe and happy holiday
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