Investment Commentary
What Everybody Ought to Know About Gilead and Johnson's New Hepatitis C Drugs
By Todd Campbell
December 6, 2013
A new class of oral drugs for curing hepatits C is hitting the markets this winter, displacing injectible predecessors and ushering in treatments that are shorter and in some cases avoid side-affect riddled interferon.
1. They work better, but not for everyone
This new class of drugs is more effective than the prior-generation injectibles, which include Incivek, now fully controlled by Johnson following Vertex's exit, and Victrelis, made by Merck. Both Gilead and Johnson's new drugs are approved for 12-week treatment courses, far shorter than the 24- to 48-week courses for those predecessors. But both Gilead's and Johnson's drugs don't cure everyone.
In studies, Gilead's sofosbuvir, which will likely be approved as a combination therapy alongside ribavirin, cured roughly 89% of patients with genotype 1, the most common genotype in America. Based on Phase 3 results, Johnson's Olysio cures 84% of cases, but stumbles in patients with the Q80K polymorphism, curing just 58%.
"Given the high frequency of the Q80K polymorphism in the U.S. population and its significant impact on rates of SVR12, DAVP is recommending that all GT1a patients be screened for the Q80K polymorphism. Alternative treatment options should be considered for patients found to be infected with this polymorphic variant," according to the FDA's advisory panel committee recommendation.
That should significantly reduce Olysio's appeal, given that nearly 50% of those with hepatitis C, genotype 1 have Q80K.
2. They come with fewer side effects, but still rely on interferon and ribavirin
The target for all of these drugmakers remains a therapy that is free of side-effect laden interferon and ribavirin. If approved on Dec. 8, Gilead's drug will do away with interferon in treating patients with hepatitis genotypes 2 and 3, but interferon will still be dosed alongside ribavirin for the majority of Americans. Meanwhile, Johnson's Olysio still relies on both interferon and ribavirin.
One of the closest to a truly interferon- and ribavirin-free therapy appears to be Bristol. Bristol's drug daclatasvir is being considered for approval in Japan for use in combination with Bristol's asunaprevir for the tough-to-treat genotype 1b population. That population accounts for 70% of Japanese hepatitis cases. and Bristol's interferon- and ribavirin-free, two-drug combination cleared the disease nearly 85% of the time.
3. Fewer pills, easier regimen
It's not just interferon and ribavirin that make it tough for patients to stick to their drug regimen -- it's the dosing, too. The dosing of multiple drugs and injections with varying treatment schedules makes it hard for patients to adhere to protocols. That can cause them to drop out of treatment, fail to clear the disease, or worse, choose to avoid treatment altogether. As a result, drugmakers are focusing on one-pill solutions.
Unfortunately, current treatments from Gilead and Johnson are multi-pill, which is better, but not ideal. However, one pill treatments should be coming soon. In November, Gilead reported data from a Phase 2 trial showing that 95% of patients were cured by a single, once-daily pill combining sofosbuvir and another Gilead drug, ledipasvir.
4. Increasingly expensive treatment
Some doctors will embrace off-label combinations of sofosbuvir with either daclatasvir or Olysio. Those combinations have shown impressive results in Phase 2 -- so impressive that European regulators have given the nod for compassionate use of daclatasvir, despite Bristol not yet filing for EU approval.
Interim data from a Phase 2 trials combining Olysio with sofosbuvir in patients with liver disease who had failed prior treatment are also remarkable. In that study, the combination delivered a 100% cure rate four weeks following a 12-week course of treatment.
While those combinations offer hope for the most critical cases, they pose a big question for patients and insurers. Analysts peg pricing of Olysio at $67,000 for 12 weeks, and estimates for sofosbuvir are running as high as $100,000 for 12 weeks. For comparison, the cost to treat patients with an interferon and ribavirin combination runs roughly $15,000 to $20,000.
5. Hypercompetitive marketplace
Gilead, Johnson, and Bristol are looking over their shoulders at AbbVie and Merck. Both companies have promising late-stage trials ongoing for treating hepatitis C, with AbbVie guiding for a Q2, 2014 filing with the FDA. In a Phase 3 trial, AbbVie's 3 drug, non-interferon, combination cured 95% of patients with genotype 1. And Merck's MK-5172, combined with MK-8742, produced a cure rate between 96% and 100% in a small Phase 2 trial, prompting the FDA to grant the therapy breakthrough status.
That means investors, patients, and doctors have a lot to consider over the coming year as all these contenders vie for a share of a market Express Scripts thinks will quadruple by the end of 2015.
http://www.fool.com/investing/general/2013/12/06/what-everybody-ought-to-know-about-gilead-and-john.aspx
Friday, December 6, 2013
Thursday, December 5, 2013
Need Help Paying For Simeprevir (Olysio): J & J Patient Access Programs
Simeprevir (Olysio): J & J Patient Access Programs
Hello, folks, and how are you all feeling today? I hope, healthy, happy and ready to take on the day.
I just came from visiting NATAP , a website that pretty much is like an online library, with a database of information including current news articles and comprehensive research on the development of promising new HCV medications.
Today, the site offered information on J&J's patient assistance program for Simeprevir (Olysio)
The program will help people who are interested in treating with simeprevir, but do not have prescription coverage and the financial means to do so.
Remember, patients can turn over the enrollment process to their healthcare providers.
To find out more about eligibility, requirements, and restrictions, begin here.
Hello, folks, and how are you all feeling today? I hope, healthy, happy and ready to take on the day.I just came from visiting NATAP , a website that pretty much is like an online library, with a database of information including current news articles and comprehensive research on the development of promising new HCV medications.
Today, the site offered information on J&J's patient assistance program for Simeprevir (Olysio)
The program will help people who are interested in treating with simeprevir, but do not have prescription coverage and the financial means to do so.
Remember, patients can turn over the enrollment process to their healthcare providers.
To find out more about eligibility, requirements, and restrictions, begin here.
Video - Dr. Joseph Galati talks about HCV drug OLYSIO (simeprevir)
Published on Dec 2, 2013
Dr. Joseph Galati with Liver Specialists of Texas, located in Houston, in this video talks about the new hepatitis C drugs that have been FDA approved. Dr. Galati has been treating patients with hepatitis C for over 20 years, and is involved in hepatitis C research.
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 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 www.texasliver.com for additional information.
Related-
Olysio (simeprevir) - Resistant Variant (Q80K)
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 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 www.texasliver.com for additional information.
Related-
Olysio (simeprevir) - Resistant Variant (Q80K)
Do Pharma Gifts Influence Doctors
In an article over at Berkeley Wellness, David Tuller, Dr. PH., wrote about a rather difficult situation he was confronted with during a HIV meeting he attended in Boston.
The journalist was offered financial compensation indirectly from a pharmaceutical company to cover his transportation and motel costs, did he accept it?
In addition, Tuller pointed out the pharmaceutical industry supplies our doctor with pens, notepads, mugs and yep, those free drug samples stored away in your medicine cabinet. Well, he didn't imply that we have free drugs hidden in our bathroom, or that because we accepted the samples, we indirectly received compensation from a drug company, I did that all by myself.
Whenever a pharmaceutical "rep" supplies our doctor with drug-labeled calendars and other free goods, it can easily create an ethical dilemma, but then, so can we.
Do Pharma Gifts Influence Doctors?
by David Tuller, Dr.ph. | December 04, 2013
The extensive web of financial ties between drug companies and other industry groups, doctors, academic researchers and medical institutions has for decades remained largely hidden from public view. In recent years, public and political pressure toward greater transparency has led to far more disclosure of conflicts of interest in the medical profession, and in particular the large consulting fees, free trips and other goodies that drug companies sprinkle among physicians in a position to prescribe their products. For their part, peer-reviewed medical and public health journals have promulgated increasingly stringent disclosure policies for authors, although how strictly they enforce the policies is a separate question. But does disclosure alone offer the reader sufficient protection from any influence the funder might try to wield? In academic publishing, the answer is considered to be “yes.” In a non-academic publication, such sponsored material would simply be called advertising...
That last bit—about dispelling physicians’ “sense of denial”—sounds like wishful thinking to me. So until that happens, patients themselves can play their own part in pushing for greater disclosure....
Although most patients might feel uncomfortable asking their doctors if they receive financial compensation or free goods from pharmaceutical companies, medical-device makers or other commercial interests, they have a right to know....
Continue reading.........
Photo Credit - www.drugwatch.com
Tuesday, December 3, 2013
Sofosbuvir for Hepatitis C: Simpler, Shorter, Safer?
Medscape Gastroenterology
Sofosbuvir for Hepatitis C: Simpler, Shorter, Safer?
William F. Balistreri, MD
Dec 3 2013
Aiming for the Ideal Strategy
In 2011, the American Association for the Study of Liver Diseases (AASLD) issued an updated version of its practice guidelines for the treatment of chronic genotype 1 hepatitis C virus (HCV) infection.[1] The current standard-of-care regimens include a protease inhibitor -- telaprevir or boceprevir -- in combination with pegylated interferon (PEG-IFN) and ribavirin. Protease inhibitor-based strategies for patients with genotype 1 HCV have led to high rates of sustained virologic response (SVR); however, there are several recurring concerns.
The disadvantages of IFN treatment are well known. Moreover, this strategy presents a complex and prolonged therapeutic course (24-48 weeks), low tolerability, a low barrier to resistance, and reduced efficacy in prior null responders or cirrhotic patients. These regimens are not an option for many patients because of contraindications or intolerability to IFN.[2-7]
To address these concerns, there has been a massive effort to create the ideal agent or strategy for use in updated therapeutic efforts. The pace of discovery has been unprecedented, and several agents are in the later phases of development. The approach has been to discover drugs that directly target various aspects of the HCV life cycle -- hopefully leading to combinations of agents that will more effectively treat patients, while minimizing intolerable side effects or adverse events
Sofosbuvir Enters the Fray
A recent article discussed simeprevir, an HCV NS3/4A protease inhibitor. [Editor's note: The US Food and Drug Administration (FDA) approved simeprevir (Olysio™) on November 22, 2013.]
The latest drug to emerge from this effort is sofosbuvir. In late October, an FDA advisory panel recommended the approval of sofosbuvir for the treatment of 2 groups of patients with chronic HCV: previously untreated adults with genotypes 1 and 4 infections (in combination with PEG-IFN and ribavirin) and adults with genotype 2 and 3 infections (in combination with ribavirin alone), which would allow an all-oral, IFN-free treatment for these 2 genotypes.
Sofosbuvir, an orally administered nucleotide analogue inhibitor of the HCV NS5B polymerase, exerts potent antiviral activity against HCV genotypes 1 through 6. This drug is meant to be taken once daily at a dose of 400 mg. Sofosbuvir has been extensively studied in various patient populations in combination with PEG-IFN/ribavirin, as well as with other direct-acting antiviral agents in treatment-naive patients with genotype 1 HCV infection.[8-12]
The FDA advisory committee reviewed primary efficacy and safety data from a series of clinical trials. The data supported the possibility of effectively treating HCV infection with a brief, well-tolerated, all-oral, once-daily regimen that has no known safety issues and no resistance development. Phase 3 trials of sofosbuvir in treatment-naive patients with hepatitis C virus genotypes 1 through 6 demonstrated that patients with genotype 1 infection have excellent treatment response that is superior overall to published response rates for combination therapy and currently available triple therapies. For patients with genotypes 2 and 3, efficacy was similar between an IFN-free sofosbuvir regimen and a standard PEG-IFN/ribavirin regimen.
Evidence for Sofosbuvir
Numerous studies have emerged; a brief overview of a few representative studies of sofosbuvir in combination with other direct-acting antiviral agents is offered here:
• Sofosbuvir was combined with simeprevir with and without ribavirin; SVR rates of 93%-96% were reported.[11]
• Sofosbuvir plus the NS5A inhibitor daclatasvir led to SVR at 12 weeks (SVR12) rates of 86%-100%.[13]
• Ledipasvir is a novel HCV NS5A inhibitor that has shown potent antiviral activity against genotypes 1a and 1b HCV infection.[14,15] It is active against HCV with the S282T mutation, the only variant known to reduce susceptibility to sofosbuvir.[16] All treatment-naive patients and prior null responders (noncirrhotic) who received 12 weeks of sofosbuvir and ledipasvir plus ribavirin achieved high SVR12 rates (95%-100%). Patients treated for 12 weeks had a similar response to patients who received 8 weeks of therapy, suggesting that this shorter treatment strategy might be sufficient for noncirrhotic patients who have not previously been treated for HCV.
In all of these studies, sofosbuvir was well tolerated, with a low incidence of adverse events. In conjunction with the suggested brief duration of this regimen, this indicates that drug combinations should improve treatment adherence compared with IFN-based treatment. Traditional predictors of response, such as IL28B genotype and baseline viral load, do not seem to affect response rates. Other large multicenter trials are under way, designed to address the optimal treatment combination and duration, the need for ribavirin, and the efficacy in patients with compensated cirrhosis in both treatment-naive and previously treated patients.
Data on the Drug
Presentations offered at the AASLD's Liver Meeting 2013 abetted the data submitted to the FDA. Several studies reported pan-genotypic efficacy and safety of sofosbuvir, as well as other potential uses for this agent in various drug combinations and in various populations, including the following:
• In a phase 3 trial, 12 weeks of sofosbuvir plus ribavirin demonstrated high SVR rates in a predominantly treatment-experienced patient population with genotypes 2 and 3 HCV infection, with higher response rates in patients infected with genotype 2 than in those infected with genotype 3 HCV.[17]
• In a phase 2, randomized, open-label study, the combination of sofosbuvir plus simeprevir plus ribavirin for 12 or 24 weeks in patients with HCV genotype 1 infection resulted in high SVRs. This study included null responders and patients with cirrhosis.[18]
• Sofosbuvir plus ledipasvir given in a fixed combination elicited a rapid decline in HCV RNA levels in all patient populations, with no viral breakthrough. In treatment-naive patients with genotype 1 infection and without cirrhosis, a reduction in duration of therapy from 12 to 6 weeks increased the rate of relapse.[19] In genotype 1-infected patients who were prior null responders and had cirrhosis, the addition of ribavirin to sofosbuvir and ledipasvir reduced the rate of relapse.
• Treatment-naive patients with HCV genotype 2 and 3 who were coinfected with HIV achieved high SVR12 rates with an IFN-free, oral regimen of sofosbuvir plus ribavirin.[20] The SVR12 rates were 76% among patients with HCV genotype 1, 88% among those with genotype 2, and 67% among those with genotype 3; these are similar to the rates observed for patients infected with HCV only. These preliminary data suggest that sofosbuvir plus ribavirin treatment was well tolerated and safe, even with the coadministration of multiple antiretroviral drugs.
A Markov model, developed to evaluate the long-term outcomes of sofosbuvir-based therapy for HCV infection, indicated that regimens incorporating this agent are highly effective in preventing progression to advanced liver disease.[21]
New Opportunities Bring New Challenges
Recurrence of HCV infection is the most common cause of graft loss and mortality in HCV-infected liver transplant recipients. IFN-based post-transplantation antiviral regimens, including those using protease inhibitors, are poorly tolerated and achieve SVRs that are lower than those in nontransplant patients.
Administration of sofosbuvir plus ribavirin after liver transplantation in the setting of established HCV recurrence was well tolerated, and approximately 80% of patients achieved an early SVR at 4 weeks. There were no episodes of rejection or drug interaction, and there was no apparent effect of sofosbuvir on serum levels of immunosuppressive medications, offering the potential for an all-oral therapy for treatment of HCV infection after liver transplantation.[22] Sofosbuvir and ribavirin may, in fact, be used in the pretransplant phase to prevent recurrence of HCV infection after transplantation.[23]
In summary, 2 novel direct-acting antiviral agents -- sofosbuvir and simeprevir -- target various components of the HCV genome. Advantages of these drugs include a high barrier to viral resistance, a shorter duration of treatment, once-daily dosing, absence of food restrictions, few clinically significant drug interactions, and similar efficacy in all genotypes. This will offer clinicians new options as well as new challenges. A recent review addressed some of these anticipated issues, such as the off-label use of HCV medications and the roles of the FDA, consumer pressure, medical society guidelines, and third-party payers.[24]
The availability of these agents will provide unprecedented opportunities for off-label use of these therapies in many patients, including those with decompensated cirrhosis or chronic kidney disease, pediatric populations, and those with HIV coinfection. Because many of these populations represent relatively small numbers of patients with HCV, it may be difficult to accumulate the requisite data and possibly cost-prohibitive for manufacturers to apply for FDA approval.
The bottom line is that simpler, shorter, and safer strategies for treatment of patients infected with HCV are at hand.
http://www.medscape.com/viewarticle/815115_4
Sofosbuvir for Hepatitis C: Simpler, Shorter, Safer?
William F. Balistreri, MD
Dec 3 2013
Aiming for the Ideal Strategy
In 2011, the American Association for the Study of Liver Diseases (AASLD) issued an updated version of its practice guidelines for the treatment of chronic genotype 1 hepatitis C virus (HCV) infection.[1] The current standard-of-care regimens include a protease inhibitor -- telaprevir or boceprevir -- in combination with pegylated interferon (PEG-IFN) and ribavirin. Protease inhibitor-based strategies for patients with genotype 1 HCV have led to high rates of sustained virologic response (SVR); however, there are several recurring concerns.
The disadvantages of IFN treatment are well known. Moreover, this strategy presents a complex and prolonged therapeutic course (24-48 weeks), low tolerability, a low barrier to resistance, and reduced efficacy in prior null responders or cirrhotic patients. These regimens are not an option for many patients because of contraindications or intolerability to IFN.[2-7]
To address these concerns, there has been a massive effort to create the ideal agent or strategy for use in updated therapeutic efforts. The pace of discovery has been unprecedented, and several agents are in the later phases of development. The approach has been to discover drugs that directly target various aspects of the HCV life cycle -- hopefully leading to combinations of agents that will more effectively treat patients, while minimizing intolerable side effects or adverse events
Sofosbuvir Enters the Fray
A recent article discussed simeprevir, an HCV NS3/4A protease inhibitor. [Editor's note: The US Food and Drug Administration (FDA) approved simeprevir (Olysio™) on November 22, 2013.]
The latest drug to emerge from this effort is sofosbuvir. In late October, an FDA advisory panel recommended the approval of sofosbuvir for the treatment of 2 groups of patients with chronic HCV: previously untreated adults with genotypes 1 and 4 infections (in combination with PEG-IFN and ribavirin) and adults with genotype 2 and 3 infections (in combination with ribavirin alone), which would allow an all-oral, IFN-free treatment for these 2 genotypes.
Sofosbuvir, an orally administered nucleotide analogue inhibitor of the HCV NS5B polymerase, exerts potent antiviral activity against HCV genotypes 1 through 6. This drug is meant to be taken once daily at a dose of 400 mg. Sofosbuvir has been extensively studied in various patient populations in combination with PEG-IFN/ribavirin, as well as with other direct-acting antiviral agents in treatment-naive patients with genotype 1 HCV infection.[8-12]
The FDA advisory committee reviewed primary efficacy and safety data from a series of clinical trials. The data supported the possibility of effectively treating HCV infection with a brief, well-tolerated, all-oral, once-daily regimen that has no known safety issues and no resistance development. Phase 3 trials of sofosbuvir in treatment-naive patients with hepatitis C virus genotypes 1 through 6 demonstrated that patients with genotype 1 infection have excellent treatment response that is superior overall to published response rates for combination therapy and currently available triple therapies. For patients with genotypes 2 and 3, efficacy was similar between an IFN-free sofosbuvir regimen and a standard PEG-IFN/ribavirin regimen.
Evidence for Sofosbuvir
Numerous studies have emerged; a brief overview of a few representative studies of sofosbuvir in combination with other direct-acting antiviral agents is offered here:
• Sofosbuvir was combined with simeprevir with and without ribavirin; SVR rates of 93%-96% were reported.[11]
• Sofosbuvir plus the NS5A inhibitor daclatasvir led to SVR at 12 weeks (SVR12) rates of 86%-100%.[13]
• Ledipasvir is a novel HCV NS5A inhibitor that has shown potent antiviral activity against genotypes 1a and 1b HCV infection.[14,15] It is active against HCV with the S282T mutation, the only variant known to reduce susceptibility to sofosbuvir.[16] All treatment-naive patients and prior null responders (noncirrhotic) who received 12 weeks of sofosbuvir and ledipasvir plus ribavirin achieved high SVR12 rates (95%-100%). Patients treated for 12 weeks had a similar response to patients who received 8 weeks of therapy, suggesting that this shorter treatment strategy might be sufficient for noncirrhotic patients who have not previously been treated for HCV.
In all of these studies, sofosbuvir was well tolerated, with a low incidence of adverse events. In conjunction with the suggested brief duration of this regimen, this indicates that drug combinations should improve treatment adherence compared with IFN-based treatment. Traditional predictors of response, such as IL28B genotype and baseline viral load, do not seem to affect response rates. Other large multicenter trials are under way, designed to address the optimal treatment combination and duration, the need for ribavirin, and the efficacy in patients with compensated cirrhosis in both treatment-naive and previously treated patients.
Data on the Drug
Presentations offered at the AASLD's Liver Meeting 2013 abetted the data submitted to the FDA. Several studies reported pan-genotypic efficacy and safety of sofosbuvir, as well as other potential uses for this agent in various drug combinations and in various populations, including the following:
• In a phase 3 trial, 12 weeks of sofosbuvir plus ribavirin demonstrated high SVR rates in a predominantly treatment-experienced patient population with genotypes 2 and 3 HCV infection, with higher response rates in patients infected with genotype 2 than in those infected with genotype 3 HCV.[17]
• In a phase 2, randomized, open-label study, the combination of sofosbuvir plus simeprevir plus ribavirin for 12 or 24 weeks in patients with HCV genotype 1 infection resulted in high SVRs. This study included null responders and patients with cirrhosis.[18]
• Sofosbuvir plus ledipasvir given in a fixed combination elicited a rapid decline in HCV RNA levels in all patient populations, with no viral breakthrough. In treatment-naive patients with genotype 1 infection and without cirrhosis, a reduction in duration of therapy from 12 to 6 weeks increased the rate of relapse.[19] In genotype 1-infected patients who were prior null responders and had cirrhosis, the addition of ribavirin to sofosbuvir and ledipasvir reduced the rate of relapse.
• Treatment-naive patients with HCV genotype 2 and 3 who were coinfected with HIV achieved high SVR12 rates with an IFN-free, oral regimen of sofosbuvir plus ribavirin.[20] The SVR12 rates were 76% among patients with HCV genotype 1, 88% among those with genotype 2, and 67% among those with genotype 3; these are similar to the rates observed for patients infected with HCV only. These preliminary data suggest that sofosbuvir plus ribavirin treatment was well tolerated and safe, even with the coadministration of multiple antiretroviral drugs.
A Markov model, developed to evaluate the long-term outcomes of sofosbuvir-based therapy for HCV infection, indicated that regimens incorporating this agent are highly effective in preventing progression to advanced liver disease.[21]
New Opportunities Bring New Challenges
Recurrence of HCV infection is the most common cause of graft loss and mortality in HCV-infected liver transplant recipients. IFN-based post-transplantation antiviral regimens, including those using protease inhibitors, are poorly tolerated and achieve SVRs that are lower than those in nontransplant patients.
Administration of sofosbuvir plus ribavirin after liver transplantation in the setting of established HCV recurrence was well tolerated, and approximately 80% of patients achieved an early SVR at 4 weeks. There were no episodes of rejection or drug interaction, and there was no apparent effect of sofosbuvir on serum levels of immunosuppressive medications, offering the potential for an all-oral therapy for treatment of HCV infection after liver transplantation.[22] Sofosbuvir and ribavirin may, in fact, be used in the pretransplant phase to prevent recurrence of HCV infection after transplantation.[23]
In summary, 2 novel direct-acting antiviral agents -- sofosbuvir and simeprevir -- target various components of the HCV genome. Advantages of these drugs include a high barrier to viral resistance, a shorter duration of treatment, once-daily dosing, absence of food restrictions, few clinically significant drug interactions, and similar efficacy in all genotypes. This will offer clinicians new options as well as new challenges. A recent review addressed some of these anticipated issues, such as the off-label use of HCV medications and the roles of the FDA, consumer pressure, medical society guidelines, and third-party payers.[24]
The availability of these agents will provide unprecedented opportunities for off-label use of these therapies in many patients, including those with decompensated cirrhosis or chronic kidney disease, pediatric populations, and those with HIV coinfection. Because many of these populations represent relatively small numbers of patients with HCV, it may be difficult to accumulate the requisite data and possibly cost-prohibitive for manufacturers to apply for FDA approval.
The bottom line is that simpler, shorter, and safer strategies for treatment of patients infected with HCV are at hand.
http://www.medscape.com/viewarticle/815115_4
Olysio (simeprevir) - Resistant Variant (Q80K)
Resistant Variant (Q80K)
Good morning everyone, while we're all waiting this week for news from the FDA on Gilead's sofosbuvir, LabCorp has captured our attention with a press release announcing the company's enhanced version of a drug resistance test used to screen for the Q80K polymorphism; a naturally occurring polymorphism that develops in certain strains of HCV, making the virus less susceptible to Janssen Therapeutics' OLYSIO(TM) (simeprevir), Quest Diagnostics also offers the Hepatitis C Viral RNA NS3 genotype test.
OLYSIO™ (simeprevir) - Q80K polymorphism
Last month, Olysio (simeprevir), the first "second wave direct-acting antiviral" was FDA approved in combination with peginterferon alfa and ribavirin to treat HCV genotype 1, adults, with compensated liver disease, including cirrhosis, who are treatment-naïve or who have failed previous interferon therapy (pegylated or non‑pegylated) with ribavirin. 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. Alternative therapy should be considered for people with the mutation, according to simeprevir prescribing information.
In the QUEST-1 and QUEST-2 studies, researchers reported in QUEST-1 patients with HCV genotype 1a had almost a 20% less SVR than HCV genotype 1b. As noted, at baseline, the mutation Q80K was found in approximately 1/3 of genotype 1a patients. On the contrary, in QUEST-2 this mutation was infrequent and did not impact significantly the SVR rate.
Johnson & Johnson went on to perform an analysis pooling all subjects from the C205, C206, C208, C216, and HPC3007 trials, and found 48 percent of U.S. patients with a HCV genotype 1a had the Q80K polymorphism at baseline, compared to only 19 percent of patients in Europe. The mutation is almost nonexistent in those with a genotype 1b infection.
**Notably, no Q80K-related reductions in efficacy were observed during the pivotal trials of the currently approved NS3/4A protease inhibitors, telaprevir and boceprevir.
Excerpt: OLYSIO™ (simeprevir) Receives FDA Approval for Combination Treatment of Chronic Hepatitis C, November 2013
Genotype 1a treatment-naïve patients receiving OLYSIO who had the Q80K polymorphism
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.
Table 2 presents SVR12 data by subgroups from the pooled studies in treatment-naïve subjects (C208 and C216) as well as from the trial in subjects who relapsed after prior interferon-based therapy (HPC3007). In all other subgroup analyses presented in Table 2, SVR12 rates were significantly higher in the simeprevir group compared to the Control group.
*A study of an all-oral combination of simeprevir
with Gilead's sofosbuvir has shown that the regimen mitigates the
effect Q80K has on simeprevir, Gaston Picchio, hepatitis disease area
leader at J&J's Janssen unit, said during the meeting.
Source - FDA review package for simeprevir and Johnson & Johnson document released Oct 23.
FDA review package for simeprevir is available at NATAP, no download required to view.
Monday, December 2, 2013
Medivir: HELIX-2, phase II all-oral study of Simeprevir, TMC647055 and Samatasvir (IDX719) for hepatitis C has been initiated
Press releases - Published Monday, 02 December 2013 14:11
Medivir: HELIX-2, a phase II all-oral combination study of Simeprevir, TMC647055 and Samatasvir (IDX719) for the treatment of hepatitis C has been initiated
Press release published at The Swedish Wire
Stockholm, Sweden-Medivir AB (OMX: MVIR), announces that IDENIX has initiated a phase II clinical trial (HELIX-2) evaluating an all-oral, direct-acting antiviral (DAA) HCV combination regimen of simeprevir, samatasvir and TMC647055 with a pharmacokinetic enhancer.
The HELIX-2 trial is a 12-week, randomized, open-label study evaluating the efficacy, safety and tolerability of simeprevir, TMC647055 and samatasvir. The trial will evaluate genotype 1 HCV-infected patients who are either treatment-naïve or who have relapsed after prior treatment with interferon and ribavirin. Patients will receive 75 mg of simeprevir, 50 mg samatasvir and 450 mg of TMC647055 plus a low dose of ritonavir as a pharmacokinetic enhancer, each once daily for 12 weeks, with or without the addition of ribavirin.
The HELIX-2 trial is the second study in HCV-infected patients to commence under a non-exclusive collaboration agreement between Idenix and Janssen established in January 2013. The HELIX-1 trial of samatasvir in combination with simeprevir was initiated in May 2013 and is ongoing.
For additional information about this study, please visit www.clinicaltrials.gov
For more information please contact:
Rein Piir, EVP Corporate Affairs & IR, mobile: +46 708 537 292
About Simeprevir
Simeprevir is an NS3/4A protease inhibitor jointly developed by Medivir and Janssen R&D Ireland for the treatment of chronic hepatitis C infection in combination with other antivirals in HCV genotype 1 & 4 infected subjects with compensated liver disease, including cirrhosis.
Simeprevir was approved for the treatment of genotype 1 hepatitis C in September 2013 in Japan and in the USA and Canada in November. A Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) in April 2013 by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic hepatitis C. To date, more than 3,700 patients have been treated with simeprevir in clinical trials.
About TMC647055
TMC647055 is a potent non-nucleoside hepatitis C polymerase inhibitor with broad genotypic coverage. TMC647055 is in phase II clinical development and is developed by Janssen R&D Ireland to treat chronic hepatitis C virus infections. TMC647055 is being investigated in combination with other DAA agents in all oral interferon-free regimens. There have been no treatment-emergent serious adverse events reported in the program.
About Samatasvir (IDX719)
Samatasvir is an NS5A inhibitor with low picomolar, pan-genotypic antiviral activity in vitro. To date, samatasvir has been safe and well-tolerated after single and multiple doses of up to 150 mg in healthy volunteers up to 14 days duration, and in HCV-infected patients up to 12 weeks duration. There have been no treatment-emergent serious adverse events reported in the program. Samatasvir has demonstrated potent pan-genotypic antiviral activity in HCV-infected patients with mean maximal viral load reductions up to approximately 4.0 log10 IU/mL across HCV genotypes 1-4 in a proof-of-concept, three-day monotherapy study.
About Medivir
Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. The company is also working with research and development in other areas, such as bone disorders and neuropathic pain. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.
For more information about Medivir AB, please visit the Company's website: www.medivir.com
Medivir is a collaborative and agile pharmaceutical company with an R&D focus on infectious diseases and a leading position in hepatitis C. We are passionate and uncompromising in our mission to develop and commercialize innovative pharmaceuticals that improve people's health and quality of life.
This information was distributed by Cision
Medivir: HELIX-2, a phase II all-oral combination study of Simeprevir, TMC647055 and Samatasvir (IDX719) for the treatment of hepatitis C has been initiated
Press release published at The Swedish Wire
Stockholm, Sweden-Medivir AB (OMX: MVIR), announces that IDENIX has initiated a phase II clinical trial (HELIX-2) evaluating an all-oral, direct-acting antiviral (DAA) HCV combination regimen of simeprevir, samatasvir and TMC647055 with a pharmacokinetic enhancer.
The HELIX-2 trial is a 12-week, randomized, open-label study evaluating the efficacy, safety and tolerability of simeprevir, TMC647055 and samatasvir. The trial will evaluate genotype 1 HCV-infected patients who are either treatment-naïve or who have relapsed after prior treatment with interferon and ribavirin. Patients will receive 75 mg of simeprevir, 50 mg samatasvir and 450 mg of TMC647055 plus a low dose of ritonavir as a pharmacokinetic enhancer, each once daily for 12 weeks, with or without the addition of ribavirin.
The HELIX-2 trial is the second study in HCV-infected patients to commence under a non-exclusive collaboration agreement between Idenix and Janssen established in January 2013. The HELIX-1 trial of samatasvir in combination with simeprevir was initiated in May 2013 and is ongoing.
For additional information about this study, please visit www.clinicaltrials.gov
For more information please contact:
Rein Piir, EVP Corporate Affairs & IR, mobile: +46 708 537 292
About Simeprevir
Simeprevir is an NS3/4A protease inhibitor jointly developed by Medivir and Janssen R&D Ireland for the treatment of chronic hepatitis C infection in combination with other antivirals in HCV genotype 1 & 4 infected subjects with compensated liver disease, including cirrhosis.
Simeprevir was approved for the treatment of genotype 1 hepatitis C in September 2013 in Japan and in the USA and Canada in November. A Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) in April 2013 by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic hepatitis C. To date, more than 3,700 patients have been treated with simeprevir in clinical trials.
About TMC647055
TMC647055 is a potent non-nucleoside hepatitis C polymerase inhibitor with broad genotypic coverage. TMC647055 is in phase II clinical development and is developed by Janssen R&D Ireland to treat chronic hepatitis C virus infections. TMC647055 is being investigated in combination with other DAA agents in all oral interferon-free regimens. There have been no treatment-emergent serious adverse events reported in the program.
About Samatasvir (IDX719)
Samatasvir is an NS5A inhibitor with low picomolar, pan-genotypic antiviral activity in vitro. To date, samatasvir has been safe and well-tolerated after single and multiple doses of up to 150 mg in healthy volunteers up to 14 days duration, and in HCV-infected patients up to 12 weeks duration. There have been no treatment-emergent serious adverse events reported in the program. Samatasvir has demonstrated potent pan-genotypic antiviral activity in HCV-infected patients with mean maximal viral load reductions up to approximately 4.0 log10 IU/mL across HCV genotypes 1-4 in a proof-of-concept, three-day monotherapy study.
About Medivir
Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company's key pipeline asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. The company is also working with research and development in other areas, such as bone disorders and neuropathic pain. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.
For more information about Medivir AB, please visit the Company's website: www.medivir.com
Medivir is a collaborative and agile pharmaceutical company with an R&D focus on infectious diseases and a leading position in hepatitis C. We are passionate and uncompromising in our mission to develop and commercialize innovative pharmaceuticals that improve people's health and quality of life.
This information was distributed by Cision
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