Hepatitis C Screening and Evaluation: Clinical Decision Tool

Gastroenterology
Volume 145, Issue 5 , Pages 1144-1145, November 2013

John I. Allen

Publication of the Clinical Decision Tool (CDT) for Hepatitis C Screening and Evaluation marks a milestone for the American Gastroenterological Association (AGA). This CDT is the first in a series of care pathways created for the “Clinical Service Lines” (CSL) component of AGA's “Roadmap to the Future of GI” initiative. The Roadmap to the Future of GI is designed to provide gastroenterologists with a single source for clinical tools needed to practice within the emerging value-based reimbursement environment. These tools have been created using a process steeped in the scientific rigor characteristic of AGA publications, combined with immediate access and the applicability needed for clinical practice.

The Roadmap to the Future of GI was originally presented to the AGA Governing Board during its strategy retreat in July 2011. It was first described in a July 2012 article in Clinical Gastroenterology and Hepatology¹ and subsequent sections of the AGA website (www.gastro.org). The AGA initially committed to fully develop 3 CSL including (a) Hepatitis C Screening and Evaluation; (b) Colorectal Cancer Prevention; and (c) Inflammatory Bowel Disease. Beginning components of these 3 CSL can be referenced within the Practice Section of the AGA website.

The following components populate each CSL:

1.Clinical practice guidelines

2.Clinical Decision Tool

3.Performance measures

4.Methods to collect data on performance measures

5.Guides to reimbursement

6.Patient tools

7.Professional education

Hepatitis C virus (HCV) was endorsed as an important first CSL because of the substantial impact of chronic HCV infection on the adult population, the new recommendation for population-based screening and the enormous progress made in its treatment.², ³, ⁴ Chronic HCV infection is a leading cause of liver disease, cirrhosis, hepatocellular cancer, liver transplantation, and death.⁵ Newly developed therapies, including direct acting antiviral therapies, have been developed and it is likely that therapies will become entirely oral and of shorter duration compared with traditional interferon-based treatments.⁵

Within the last year, the Centers for Disease Control and the United States Preventative Services Task Force both recommended one time screening for HCV for all people born between 1945 and 1965 in an effort to identify the 2.7–3.9 million Americans who are living with a chronic HCV infection.², ³ Seventy-six percent of those infected with HCV are contained within this age group, and an estimated 45%–85% of those people with HCV are unaware they are infected, with 15%–40% expected to eventually develop cirrhosis or cancer.

It is clear that the burden of age cohort-based HCV screening, not to mention subsequent management of screen-positive patients, will overwhelm the capacity of United States hepatologists. General gastroenterologists must engage in HCV management to the highest level of their comfort. As a result of this sobering realization, the AGA, in partnership with the American Association for Study of Liver Disease (AASLD), set out to develop an easy-to-use care pathway with evidence-based recommendations for managing the initial phase of HCV evaluation.

An initial advisory group met in October 2012 in Chicago, IL. The final Task Force (listed at the end of this article) developed the CDT and evaluated each of its 15 decision points as part of a series of meetings and teleconferences from January to June of 2013. We gratefully acknowledge the participation of physician leaders and staff from the AGA, AASLD, and the Infectious Disease Society of America, plus practice leaders from both academic and community gastroenterology practices.

This CDT will aid gastroenterologists in the early management of HCV-positive patients and is intended to become a map for both clinical practice and construction of standard order sets, alerts, and dynamic point of care feedback within electronic medical records. The unique aspect of this CDT is that each decision point was evaluated and graded for its strength of evidence and strength of recommendation. Using the CDT, gastroenterologists can complete an evidence-based, cost-effective initial evaluation of patients whose screening for HCV is positive. It is important to emphasize that initial HCV screening positivity is not sufficient to begin therapy since further testing should confirm infection and must be coupled with expert evaluation of liver status including inflammation and histologic stage. Treatment of HCV infection was not included in this CDT since therapies are changing rapidly, however, care delivery infrastructure will need to adapt quickly in order to manage the number of expected HCV infected patients and the complexities of emerging therapies. Programs like Extension for Community Healthcare Outcomes (ECHO), represent a model of treatment that might help with capacity management.⁶

As the United States moves into a health care delivery world constrained by financial pressures and characterized by accountable care, risk contracting for population management, and reimbursements tied to outcomes, the tools created by the AGA will aid gastroenterologists to redesign their practice to meet these challenges. AGA leadership and staff hope that clinical decision tools like this and other tools within the Roadmap to the Future of GI will support the critical role that gastroenterologists play in providing care for the people that entrust us with their lives and health.

Appendix

The Hepatitis C Task Force includes: Mark D. Boldt, RN, CNP, Minnesota Gastroenterology; Joel V. Brill, MD, AGAF, Predictive Health; Gary L. Davis, MD, Baylor University Medical Center Dallas(retired); Stuart C. Gordon, MD, AGAF, Henry Ford Health System; Arthur Y. Kim, MD, FIDSA, Massachusetts General Hospital; Lawrence R. Kosinski, MD, MBA, AGAF, Illinois Gastroenterology Group; Arnold G. Levy, MD, Capital Digestive Care; Ronald G. Nahass, MD, MHCM, FIDSA, ID Care; John I. Allen, MD, MBA, AGAF (Chair), Yale School of Medicine.

References

Conflicts of interest The author discloses no conflicts.

PII: S0016-5085(13)01286-9

doi:10.1053/j.gastro.2013.09.008

© 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Source

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Gastroenterology
Volume 145, Issue 5 , Pages 1146-1149, November 2013

Hepatitis C Screening: Summary of Recommendations From the Clinical Decision Tool

The Hepatitis C Task Force, Mark D. Boldt, RN, CNP, Joel V. Brill, MD, AGAF, Gary L. Davis, MD, Stuart C. Gordon, MD, AGAF, Arthur Y. Kim, MD, FIDSA, Lawrence R. Kosinski, MD, MBA, AGAF, Arnold G. Levy, MD, Ronald G. Nahass, MD, MHCM, FIDSA, John I. Allen, MD, MBA, AGAF (Chair)

Decision Point 1: Adults Born Between 1945–1965 Who Have Never Been Evaluated for HCV 

Strong Recommendation Based on Strong Evidence

•Adults born between 1945 and 1965 should receive one-time testing for HCV without prior ascertainment of HCV risk (CDC Recommendation).¹

•The US Preventive Services Task Force (USPSTF) recommends that clinicians consider offering screening for HCV infection in adults born between 1945 and 1965 (USPSTF GRADE B recommendation).²

Decision Point 2: Those at High Risk, Including Any Blood Transfusions Prior to 1992, or History of Intravenous Drug Use 

Strong Recommendation Based on Strong Evidence

•The USPSTF recommends screening for HCV infection in adults at high risk, including those with any history of intravenous drug use or blood transfusions prior to 1992 (USPSTF GRADE B Recommendation).²

Decision Point 3: Testing for Current Intravenous Drug Users 

Strong Recommendation based on Strong Evidence

•The USPSTF recommends screening for HCV infection in adults at high risk, including those with any history of intravenous drug use or blood transfusions prior to 1992 (USPSTF Grade B recommendation).²

Decision Point 4: Hepatitis C Antibody Testing 

Strong Recommendation Based on Strong Evidence

•A person whose anti-HCV test is reactive should be considered to either (1) have current HCV infection or (2) have had HCV infection in the past that has subsequently resolved (ie, cleared). To identify persons with active HCV infection, persons who initially test anti-HCV positive should be tested by an HCV nucleic acid test (NAT).²

Decision Point 5: Quantitative HCV RNA Testing 

Strong Recommendation Based on Strong Evidence

•HCV ribonucleic acid (RNA) testing should be performed in:

(a)Patients with a positive anti-HCV test (Class IB).

(b)Patients for whom antiviral treatment is being considered, using a sensitive quantitative assay (Class IA).

(c)Patients with unexplained liver disease whose anti-HCV test is negative and who are immunocompromised or suspected of having acute HCV infection (Class IB).³

•HCV RNA should be tested by a highly sensitive quantitative assay at the initiation of or shortly before treatment and at week 12 of therapy, (Class I, Level A).³

•For the diagnosis of acute hepatitis C, HCV RNA testing is required since HCV RNA appears before anti-HCV antibodies may be detectable.⁴

Decision Point 6: Counseling and Retesting and Other Testing as Appropriate 

Evidence not Sufficient; Recommendation to Include is Based on Expert Opinion

•Persons who use or inject illegal drugs should be advised: To stop using and injecting drugs; to enter and complete substance abuse treatment.⁵

•Persons who are at risk for sexually transmitted diseases should be advised: That the surest way to prevent the spread of HIV infection and other STDs is to have sex with only one uninfected partner or not to have sex at all; To use latex condoms correctly and every time to protect themselves and their partners from diseases.⁵

Decision Point 7: Initial Test for HCV: Comprehensive Metabolic Panel 

Strong Recommendation Based on Strong Evidence

•Laboratory monitoring should include measurement of the serum creatinine, and ALT levels, and HCV RNA by a sensitive assay at weeks 4, 12, and 24 of treatment, 4 to 12 week intervals thereafter, the end of treatment, and 24 weeks after stopping treatment.³

Decision Point 8: Initial Test for HCV: HCV Genotype 

Strong Recommendation Based on Strong Evidence

•HCV genotyping should be performed in all HCV-infected persons prior to interferon-based treatment in order to plan for the dose and duration of therapy and to estimate the likelihood of response (Class I, Level A).³

•The HCV genotype must be assessed prior to antiviral treatment initiation and will determine the dose of ribavirin and treatment decision.⁴

Decision Point 9: Initial Test for HCV: International Normalized Ratio 

Evidence not Sufficient; Recommendation to Include is Based on Expert Opinion

•International normalized ratio recommended at baseline (anti-HCV positive), pre-treatment, and as part of ongoing monitoring if patient exhibits signs and symptoms of liver disease.⁶

Decision Point 10: Initial Test for HCV: Complete Blood Count and Differential 

Strong Recommendation Based on Strong Evidence

•Complete Blood Count and Differential recommended at baseline (anti-HCV positive), pre-treatment, and at weeks 2 and 4 of treatment, 4 to 8 week intervals thereafter, 24 weeks post-treatment, and 12 months post-treatment.⁶

Decision Point 11: Initial Test for HCV: HIV Antibody 

Evidence not Sufficient; Recommendation to Include is Based on Expert Opinion

•Because of the high prevalence of HIV/HCV co-infection, and because the management of each infection can differ in dually-infected persons, all HIV-infected persons should be tested for HCV and all HCV-infected persons with HIV risk factors should be tested for HIV.³

Decision Point 12: Initial Test for HCV: HBV Surface Antigen 

Evidence not Sufficient; Recommendation to Include is Based on Expert Opinion

•Because dual infection is associated with worse prognosis than HCV infection alone and because the management of each virus can differ in dually infected persons, all HCV-infected persons with HBV risk factors should be tested for HBV.³

Decision Point 13: Administer HAV Vaccination if No Documented Immunity 

Evidence not Sufficient; Recommendation to Include is Based on Expert Opinion

•All persons with chronic HCV infection who lack antibodies to hepatitis A and B should be offered vaccination against these 2 viral infections (Class IIa, Level C).³

Decision Point 14: Administer HBV Vaccination if No Documented Immunity 

Evidence not Sufficient; Recommendation to Include is Based on Expert Opinion

•All persons with chronic HCV infection who lack antibodies to hepatitis A and B should be offered vaccination against these 2 viral infections (Class IIa, Level C).³

Decision Point 15: Conduct Brief Alcohol Screening and Intervention as Clinically Indicated 

Strong Recommendation Based on Strong Evidence

•All persons identified with HCV infection should receive a brief alcohol screening and intervention as clinically indicated, followed by referral to appropriate care and treatment services for HCV infection and related conditions (Strong Recommendation, Moderate Quality of Evidence).¹

References

Reprint requests Address requests for reprints to: Chair, Clinical Practice and Quality Management Committee, AGA National Office, 4930 Del Ray Avenue, Bethesda, Maryland 20814. e-mail:lclote@gastro.org; telephone: (301)-272-1188.

Conflicts of interest The authors disclose the following: Stuart C. Gordon has received grant/research support from Abbvie Pharmaceuticals, Bristol-Myers Squibb, Gilead Pharmaceuticals, GlaxoSmithKline, Intercept Pharmaceuticals, Merck, and Vertex Pharmaceuticals, is a consultant/adviser for Bristol-Myers Squibb, CVS Caremark, Gilead Pharmaceuticals, Merck, Novartis, and Vertex Pharmaceuticals, and is member on the Data Monitoring Board of Tibotec/Janssen. Mark D. Boldt is on the advisory board of Gilead and Janssen. Arthur Y. Kim is a consultant for Gilead Sciences and Abbvie Pharmaceuticals and has received research grants and support from Bristol-Myers Squibb. Joel V. Brill is a member of The American Association for the Study of Liver Diseases, American Gastroenterological Association, and American Medical Association-convened Physician Consortium for Performance Improvement^® workgroup that developed the Hepatitis C Performance Measurement Set. Gary L. Davis is a member on the Data and Safety Monitoring Boards for Gilead and BMS. Ronald G. Nahass is a speaker for Merck and Vertex, completed clinical research for Merck, Gilead, Janssen, Abbvie Pharmaceuticals, and BMS and is on the advisory board for Janssen and Merck. The remaining authors disclose no conflicts.

PII: S0016-5085(13)01285-7

doi:10.1053/j.gastro.2013.09.007

© 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Source

Daclatasvir: potential role in hepatitis C

Authors: Lee C

Published Date October 2013 Volume 2013:7 Pages 1223 - 1233

DOI: http://dx.doi.org/10.2147/DDDT.S40310

Received: 29 July 2013
Accepted: 29 August 2013
Published: 16 October 2013

Choongho Lee
College of Pharmacy, Dongguk University-Seoul, Goyang, Republic of Korea

Abstract: Chronic hepatitis C virus (HCV) infection is responsible for the development of liver cirrhosis and hepatocellular carcinoma. It has been a tremendous burden on global health care systems. With the advent of a number of new direct-acting and host-targeting antiviral agents, current interferon-a- and ribavirin-based HCV therapy has started to move towards an interferon-sparing or even interferon-free strategy. In this regard, a recently identified NS5A inhibitor, daclatasvir, showed a great promise in clinical trials as another new class of direct-acting anti-HCV therapeutics, with a distinct mechanism of action. In this review, a variety of preclinical as well as clinical proof-of-concept studies of daclatasvir, including the studies of its discovery, mechanism of action, viral resistance, and host polymorphism profiles are reviewed. In addition, a role of daclatasvir in the future therapy for HCV patients is discussed briefly.

Keywords: hepatitis C virus, nonstructural protein 5A, NS5A inhibitor, hepatitis C treatment

Read full article here (PDF)

FDA panel backs approval of new protease inhibitor for hepatitis C

By: ELIZABETH MECHCATIE, Family Practice News Digital Network

10/25/13  

SILVER SPRING, MD. – A Food and Drug Administration advisory panel unanimously supported the approval of the antiviral drug simeprevir as a treatment for chronic hepatitis C.

The approval was based on the highly favorable benefit-risk profile of the drug in studies that included sustained viral response rates of 79%-80% in phase III studies of patients with chronic HCV.

At a meeting on October 24, the FDA’s Antiviral Drugs Advisory Committee voted 19-0 that simeprevir, a hepatitis C virus (HCV) protease inhibitor, in combination with pegylated interferon and ribavirin (PR), be approved for the treatment of chronic hepatitis C genotype 1 (GT1) infection in adults with compensated liver disease, including cirrhosis, who are treatment-naive or have failed previous interferon-based therapy. The dosing proposed by the manufacturer, Janssen Pharmaceutical Co., is a 150-mg capsule once a day for 12 weeks, combined with PR for 24 weeks, in patients who have never been treated for HCV and for those who have relapsed on treatment. For patients who have not responded to previous treatments, PR is continued for 48 weeks.

The panel agreed that the risk-benefit profile was favorable, and with the once-daily dose, simeprevir was much easier to take than the first-generation protease inhibitors currently approved for treating chronic HCV, telaprevir and boceprevir, which are the current standard of care and require a total of 6-12 pills a day, taken at three times a day. Simeprevir inhibits HCV NS3/4A serine protease, which is "essential for viral replication," according to Janssen.

"We clearly need better drugs, and evidence is strong that this is a better drug," said panelist Dr. Curt Hagedorn, chief of the medicine service, Central Arkansas Veterans Healthcare Services, Little Rock.

"As someone who treats patients with chronic hepatitis C every day, this regimen represents a much simpler one and much safer" than currently available treatments, added panelist Dr. Marc Ghany, staff physician in the liver disease branch of the National Institute of Diabetes, Digestive and Kidney Diseases.

Panelists, however, urged Janssen to study more black patients in postmarketing trials, since black patients were greatly underrepresented in the studies but make up a large proportion of those infected with HCV in the United States. Postmarketing studies should also evaluate the drug in Hispanics, those coinfected with HIV, pediatric patients, patients with renal failure, and more patients with cirrhosis, they added.

The main safety issue discussed was the higher rates of rashes and photosensitivity reactions associated with treatment, which the FDA has proposed be included in the warnings and precautions section of the drug’s prescribing information, including a recommendation for patients to use sun protection measures while taking the drug. The panel agreed with the FDA and the manufacturer that before starting treatment, patients with HCV genotype 1a infections should be screened for the "Q80K" viral polymorphism – which is common in the United States and was associated with lower efficacy rates in the studies.

If approved, simeprevir will be the third HCV protease inhibitor approved in the United States for treating hepatitis C. In May 2011, boceprevir (Victrelis) and telaprevir (Incivek), which are also HCV NS3/4A protease inhibitors, were approved. In addition to the number of daily pills required, adverse events associated with these drugs include anemia and rash.

In three phase III studies of almost 1,200 patients most of whom were white, with chronic HCV genotype 1 infections, who had not been treated previously or had relapsed on previous treatment, simeprevir, 150 mg once a day for 12 weeks, combined with PR, followed by PR alone for 12 or 36 weeks (depending on the patient’s response), was compared with PR alone for 48 weeks (which included a placebo for the first 12 weeks). The primary efficacy endpoint was the sustained virologic response at 12 weeks (SVR 12), defined as HCV RNA that was undetectable or was detected at a level below 25 IU/mL 12 weeks after treatment was planned to end. (In the different arms of the studies, 40%-57% of the patients had HCV genotype/subtype 1a, and 43%-59% had 1b.)

In the two studies of 785 treatment-naive patients, 80% of those treated with simeprevir achieved an SVR12, compared with 50% of controls. The "on-treatment failure" rates (those who had detectable HCV RNA at the end of treatment) were 8% of those treated with simeprevir, compared with 33% of controls. The rates of viral relapse were 12% among those on simeprevir, compared with 22% of those on placebo.

In the third study of 393 relapsers, the SVR12 rate was 79% among those on simeprevir, compared with 36% among those on PR alone. Among those on simeprevir, 3% were on-treatment failures and 19% had a viral relapse, compared with 29% and 48%, respectively, of those on placebo.

In phase III studies, fatigue, headache, and influenzalike illness, associated with PR, were the most common adverse events. The only deaths reported were in three patients treated with simeprevir after they stopped taking the drug, but were not considered related to the drug. During the first 12 weeks of treatment, dyspnea was also higher among those on simeprevir (12% vs. 8%), but so far, the cause has not been determined, according to the FDA reviewer. Hyperbilirubinemia was also higher among those on simeprevir (49% vs. 26%), mostly grade 1 and 2 abnormalities.

In the first 12 weeks in the phase III studies, rashes (including photosensitivity) were reported in 28% of those on simeprevir, vs. 20% of those on PR only. Pruritus was also more common among those on simeprevir (22% vs. 15%); 1% of patients discontinued treatment because of a rash.

Janssen is investigating the appropriate dose in people of Eastern Asian descent. Exposure in these patients is higher, and rashes, photosensitivity, and other adverse events are increased with greater drug exposures, according to the FDA. A 100-mg daily dose of simeprevir has been approved in Japan (the only country where the drug has been approved to date). The drug is also being reviewed for approval in the European Union.

Among people with chronic HCV infections in the United States, genotype 1 is the most common, accounting for 75% of cases, according to the FDA.

The FDA usually follows the recommendations of its advisory panels and is expected to make a decision on this application by Nov. 27. Members of FDA panels have been cleared of conflicts related to the product under review; occasionally, a panelist is given a waiver, but not at this meeting.

emechcatie@frontlinemedcom.com

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FDA's Hamburg on Research Investment and Clearing the Hurdles to Drug Approvals

Medscape Internal Medicine

Marrecca Fiore, Margaret Hamburg, MD
October 17, 2013

Editor's Note :
US Food and Drug Administration (FDA) Commissioner Margaret Hamburg, MD, spoke with Medscape during the recent National Health Research Forum in Washington, DC, and discussed clearing the hurdles to drug and device approvals, advancing personalized medicine, and smart spending to leverage scientific enterprise.

Medscape: Your panel today talked about "clearing the hurdles to a research and healthcare renaissance." Some researchers and clinicians see the FDA as a hurdle to getting new lifesaving medications and medical devices to patients. Can you discuss what the FDA is doing right now to streamline and speed up the drug and device approval process?

Dr. Hamburg: Sure. When you look at what is required to move an important discovery in science into a real-world product that patients and consumers want and need, obviously we play a critical role. We are responsible for reviewing the data to really examine critical questions about safety and efficacy. We see that as a clear value for patients and their families, and also for the industry sponsors of these products. Because if the product doesn't work, if it is going to cause problems, it is not in the industry's best interest either.

We need to all work together, and I think part of the discussion in the conference today was how important it is to have all the voices and perspectives represented around the table. FDA is one important player in that process, and we play a critical role because we sit in a position where we can look on one side and see what the unmet medical and public health needs are, and we can also see what is in the pipeline.

But we have an obligation to do our jobs as effectively and efficiently as possible. During my tenure as commissioner, I have worked hard to make sure that, number one, we are as engaged in the science as we can possibly be, and to make sure that we have people with the right scientific expertise and experience to appropriately review applications that come before us. More important, to engage with the scientific community early and often so that, as products are being developed, as new discoveries are moving through the pipeline, we help identify what kinds of data are going to be needed, what kinds of questions have to be asked and answered as part of the ultimate review process, and our ability to approve a drug to go into the marketplace. And we know that by working together in that way, we can actually speed the development process and the review process.

We also have to commit ourselves to making sure that our business processes are as efficient as possible so that we don't sit on applications, so that we return phone calls, so that we have the kind of mechanisms to hire the people that we need, train them properly, etc. We have focused very much on really strengthening our ability to do our job, but we see our job as part of a bigger mission to really advance biomedical product innovation.

Record Numbers of Drug and Device Approvals

Medscape: Correct me if I am wrong, but I believe you said that the FDA has actually been approving more drugs and devices than in the past.

Dr. Hamburg: In the past couple of years, we have had record numbers of new medical product approvals and, more important, we approve more drugs first. If you compare us with other countries, we approve new drugs more quickly. I think we are providing a critical and unique service to the American people.

We can always do better. We must do better, but I think one of the lessons from our panel today -- and certainly a lesson from my experience at FDA and working as a bench scientist and a healthcare provider -- is that we have to always recognize that real, sustainable progress doesn't happen by operating in a silo. We need this kind of partnership and coordination across all of the components and all of the stakeholders [in the approval process] to really make the difference we want to make.

Medscape: Turning to clinical trials, there are some who believe that the randomized, placebo-controlled trial is somewhat antiquated and not always the best method of gauging real-world results when it comes to new drugs and devices. How is the FDA working to improve the way it tests new products?

Dr. Hamburg: We are so far down that path that this question is almost irrelevant, to be honest. Obviously, the randomized controlled clinical trial is the absolute gold standard in terms of rigorous science and getting really solid answers. But there are lots of other ways to get robust scientific answers without using that, and there are many circumstances where you simply can't do a randomized controlled clinical trial for ethnical reasons or practical reasons. We look at [this kind of trial] as one tool in our toolbox, and we use many other strategies in terms of the kinds of clinical data that we will use for review.

We have also funded a lot of work in this area to really look at innovative clinical trial design, working with our academic partners and in some cases with industry. We see it as an area ripe for continuing collaboration and development of new strategies and approaches. But it is critically important, as we learn more and do more, that we become increasingly flexible and innovative in our approaches.

Advancing Personalized Medicine and Scientific Enterprise

Medscape: One of the FDA's science and research initiatives is to stimulate innovation, clinical trials, and personalized medicine. Personalized medicine and genomic medicine are becoming increasingly important in the treatment of diseases. Can you explain what is being done in this area?

Dr. Hamburg: As we learn a lot more about the underlying mechanisms of disease and the relationship of certain disease processes to certain genetic traits, we also understand that even within one disease category, responsiveness to certain treatments may be different depending on certain genetic traits of the individual -- or in the case of oncology, the tumor.

We have an opportunity now to really deepen these understandings and build on them in terms of the therapies that are developed and how they are used, and that requires some new approaches in terms of the types of therapies that are being developed and the use of diagnostics that are a companion to therapy so that you can identify the subsets of responders and nonresponders. We are very deeply immersed in these activities. We have seen a number of really exciting approvals in recent years linking the diagnostic with the therapeutic, and we have seen some dramatic translations of new scientific understandings into products for people based on this approach. We are going to see more and more as time goes on.

Medscape: Finally, what is on your wish list for the future in terms of research and research funding of drugs and devices?

Dr. Hamburg: When we look at the sort of scientific enterprise overall, the understanding and investment in regulatory science have not been adequate. I think that if we really want to be able to deliver the biomedical products that the public wants and deserves, we have to address that. My wish list would be that we at FDA could get additional resources to help fund research in critical areas that will enable us to apply the advances in science and technology more effectively to the drug development process and the drug review process, whether it is genomics or bioinformatics, bioimaging, new clinical trial designs, etc.

There is so much opportunity, but it hasn't been fully developed. We have started some centers of excellence for regulatory science in academic centers, and it has been very, very productive and very valuable. We have created new partnerships, including precompetitive collaborative research with industry academia and government, including the National Institutes of Health. All of that has demonstrated real benefit in helping to move research and development forward and getting some of these exciting new understandings of disease and health out to people in terms of new products. But it is not enough.

We really need to capitalize on the opportunities [presented at the conference] today -- that would be my wish list. Of course, the reality as we know it is that dollars are constricting, so we have to be as smart as possible about leveraging resources. Part of what we talked about in the conference today was that we are going to have to make some hard choices. We are going to have to think about how we spend limited dollars, but I think that we really need to recognize that this arena of regulatory science is so key, and that it has been the weakest link in the chain of science that is necessary to truly realize the potential of science today.

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Can liver transplantation provide the statistical cure?

Liver Transplantation

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Original Article

A. Cucchetti M.D^1,*, A. Vitale M.D., Ph.D.², M. Cescon M.D. Ph.D.¹, M. Gambato MD³, L. Maroni M.D.¹, M. Ravaioli M.D. Ph.D.¹, G. Ercolani M.D.¹, P. Burra M.D., Ph.D.³, U. Cillo M.D., Ph.D.², A.D. Pinna M.D. Ph.D.¹

DOI: 10.1002/lt.23783

Publication History
Accepted manuscript online: 26 OCT 2013 04:38AM EST
Manuscript Accepted: 19 OCT 2013
Manuscript Revised: 16 SEP 2013
Manuscript Received: 25 JUN 2013

©2013. American Association for the Study of Liver Diseases

Keywords:Liver transplantation; cure model; relative survival; excess hazard rate

ABSTRACT

Liver transplantation (LT) represents the only chance of long-term survival for patients with end-stage liver disease. When the mortality among transplanted patients returns to the same level as in the general population, they can be considered “statistically cured”. However, cure models in the setting of LT have never been applied. Data from 1371 adult patients, undergoing a first LT between January 1999 and December 2012 at two Italian centers, were reviewed in order to establish probabilities of being cured by LT. A parametric Weibull model was applied to compare mortality after LT to that expected in the general population, matched by sex and age. The observed 3-, 5- and 10-year overall survival after LT was 77.8%, 73.3% and 65.6%, respectively, and did not differ between the two centers (P=0.366). The cure fraction for the entire study population was 63.4% (95%CI: 52.6%–72.0%) and the time-to-cure was 10 years with 90% of confidence level. The best cure fraction was observed for younger non-hepatitis C (HCV) recipients with favorable donor-recipient match, namely low Donor-Model for End-stage Liver Disease (D-MELD) scores (90.1%); conversely, the lowest probability was observed in elderly HCV recipients with high D-MELD scores (34.6%). The time-to-cure was 6.22 years for non-HCV patients and 14.78 years for HCV patients. Median survival of “uncured” patients was 2.29 years. Among uncured recipients, the longest survival was observed for younger patients (7.31 years). In conclusion, we provide here a new clinical measure in the LT scenario that suggests that survival after transplantation can approximate that of general population, providing the “statistical cure”. Liver Transpl , 2013. © 2013 AASLD.

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Alcoholism is a complicating factor for women with hepatitis C

By Tele management

TeleManagement) Women with hepatitis C lose survival advantage over men if they drink heavily.
Hepatitis C is a chronic infection of the liver which is passed on through contaminated blood and often linked with drug use. It sometimes leads to severe liver damage and liver cancer. Previous research has suggested that hepatitis C progresses more slowly among women, giving them a survival advantage. Drinking, to the point of alcoholism, on the other hand, worsens the outcome.

Researchers for the National Institute on Alcohol Abuse and Alcoholism put together these trends to look at the outcome for women with both hepatitis C and alcoholism. They analyzed 132,468 deaths related to hepatitis C or alcoholism. Women with hepatitis C who were not heavy drinkers died at an average age of 61. Those women with both hepatitis C and alcoholism died at an average age of 49. For men, the corresponding average ages at death were 55 and 50 years. Therefore, alcoholism wipes out the gender advantage women have over men when it comes to survival from hepatitis C. The researchers admit the study has one limitation – alcoholism often precludes access to treatment for hepatitis C because those affected are less likely to benefit. This may be a contributing factor to the lower survival rates seen when hepatitis C and alcoholism are combined.

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Organs From High Risk Patients May Be Okay for Donation

Transplants of high risk donor kidneys had no sign of HIV or hepatitis infection years later

October 25, 2013

(dailyRx News) People at risk for certain infectious diseases are usually disqualified from being blood donors. However, new research suggests that they may still be safe organ donors.

A recent study looked at organ recipients who received organs from donors who were at high-risk for infection with HIV or the hepatitis viruses B and C.

The results of the study showed that the vast majority of these organ recipients were doing well and showed no signs of infection more than two years later.

Moya Gallagher, RN, from New York-Presbyterian Hospital/Columbia University Medical Center, led this investigation into organ selection guidelines for donors who may have had certain types of infections.

According to the authors of this study, roughly 10 percent of kidneys procured for organ donation met the criteria laid out by the Centers for Disease Control and Prevention (CDC) as “high-risk” for infection and possible transference of the disease to the organ recipient.

High-risk infections included human immunodeficiency virus (HIV), hepatitis C (HCV) and hepatitis B (HBV).

For this study, the researchers looked at 170 organ transplant patients who had been given a kidney from a donor with a high-risk for infection. 

All of the recipient patients were given the standard of care immunosuppressive medications for organ transplant recipients.

Most of the patients had been on an organ wait list for an average of 1.7 years and 27.7 percent of them experienced some level of delayed function with the organ after transplant.

Among the organ donors, 57.1 percent had a history of injected drug use, 25.9 percent had a history of high-risk sexual behavior, 11.8 percent had been in prison or jail, 7.1 percent of the men had a history homosexual intercourse and 4.7 percent had received several blood transfusions.

After 2.4 years from the time of the organ transplant, 86.5 percent of the organ recipients were doing well with no evidence of having picked up the infection present in the organ donor.

The study authors concluded that all 170 of the high-risk organs were relatively safe for the recipients, and that donors with risk factors for HIV, HCV or HBV should be labeled as “identified risk” instead of “high risk.”

“Utilization of these organs represents an opportunity for shortening wait time for patients while providing good outcomes and an extremely low level of risk for transmission of infections,” Gallagher said in a press statement.

Michelle Segovia, Senior Communications Coordinator for the northern region of the Texas Organ Sharing Alliance (TOSA), said "Organ Procurement Organizations (OPO) conduct extensive medical screenings to assess the quality of organs and identify the risk of transmittable diseases such as HIV and Hepatitis B and C. At our organization, HIV would be an automatic rule out for donation but donors with Hepatitis B and C can certainly donate to a patient who already has Hepatitis."

She continued, "There are more than 120,000 people awaiting a life-saving transplant in this country and 19 die each day because of the drastic organ shortage. Transplant centers, OPOs and the CDC recognize that a patient’s risk of dying without a transplant is often much higher than the possible risk of acquiring a disease."

This study was presented at the American Society of Nephrology Kidney Week 2013 in Atlanta, Georgia. This study has not yet been published in a peer-reviewed journal.

Several of the study's co-authors reported potential conflicts of interest with Alexion, Novartis, Pfizer, Genetech, Gambro, Quark, Bristol Myers Squibb, Genzyme, Astelas and Sandoz.

Source

Gilead's hepatitis C 'cure' moves ahead at FDA

Oct 25, 2013, 2:49pm PDT Updated: Oct 25, 2013, 3:05pm PDT

Gilead's Norbert Bischofberger: Sofosbuvir is aimed at curing hepatitis C.

Ron Leuty
Reporter- San Francisco Business Times

A kinder, gentler hepatitis C treatment from Gilead Sciences Inc. — seen as a potential cure for the debilitating and deadly liver disease — was green-lighted Friday by an FDA advisory panel.

The Food and Drug Administration isn't required to follow the committee's recommendation — which was unanimous in this case — but often does. What's more, FDA staff gave the drug, called sofosbuvir, a favorable review earlier this week.

The FDA is expected to approve the drug — actually a once-a-day combination of sofobuvir with antiviral ribavirin in adults with chronic hepatitis C with genotype 2 and 3 infection — by Dec. 8.

Foster City-based Gilead (NASDAQ: GILD) acquired the drug as part of its $11 billion January 2011 buyout of Pharmasset Inc. But the initial use of the drug is only the first step toward a crucial one-pill oral cure for the leading cause of liver cancer. Gilead is working on a combination of sofoxbuvir and another drug it is developing, called ledipasvir, that targets the largest subset of hepatitis C patients.

Gilead, led by CEO John Martin, hopes to follow up that with another once-daily combination, called GS-5816, aimed at obliterating the virus in all hepatitis C patients.

"This could potentially eliminate hepatitis C from the face of the earth," Gilead Chief Scientific Officer Norbert Bischofberger told the San Francisco Business Times earlier this year.

Gilead has faced criticism from some patients and their advocates, however, because it opted not to work with Bristol-Myers Squibb, Pharmasset's one-time partner.

Gilead also is seeking approval of sofosbuvir in the European Union, Canada, Australia, New Zealand, Switzerland and Turkey.

Sofosbuvir is part of a new class of hepatitis C treatments — nicknamed "nucs" — that block a specific enzyme of the virus. Besides stunning cure rates from clinical trials, nucs are important because they could shift patients from today's treatment of weekly injections of interferon and ribavirin to an all-oral cure.

An easily dosed cure, Gilead and others say, would increase the number of patients who stay on therapy. The interfron-ribavirin treatment is so brutal, they say, that only about half of patients who start therapy continue with it.

"One argument for not collaborating is, if you do it yourself, you can move faster," Bischofberger told the Business Times earlier this year. "Patients will benefit from this single pill much sooner than in a collaboration."

Gilead stock closed down 15 cents to $69.68 per share, near its 52-week high of $70.30.

Source

Gilead’s Hepatitis C Pill Wins Backing From U.S. Advisers

By Anna Edney - Oct 25, 2013 4:05 PM ET

Gilead Sciences Inc. (GILD) won the backing of U.S. advisers for its hepatitis C pill, helping solidify the company’s drive to lead the growing market for drugs to defeat the disease.

Gilead’s drug, known as sofosbuvir, should be approved, a panel of outside advisers to the Food and Drug Administration voted unanimously today in Silver Spring, Maryland. The FDA is expected to decide whether to clear sofosbuvir for sale by Dec. 8. The agency doesn’t have to follow the panel’s advice.

Gilead, Johnson & Johnson, AbbVie Inc. (ABBV) and Bristol Myers Squibb Co. are among companies working on new hepatitis C drugs that alleviate the burden of current treatments that include interferon injections, which can cause flu-like symptoms. The market for hepatitis C medicines may reach more than $100 billion over a decade, according to Bloomberg Industries.

“This is a historic vote,” said Daniel Raymond, the consumer representative on the panel and policy director at the Harm Reduction Coalition in New York. “This is the first vote for a interferon-free regimen to treat hepatitis C. This is going to be a very important move forward.”

About 4 million Americans have hepatitis C, which can cause liver cirrhosis, according to the National Institutes of Health. The disease, which is classified into six genotypes, can be passed through infected blood or body fluids, most commonly through needle-sharing by drug users.

First Request

Gilead is seeking approval of once-daily sofosbuvir for patients with the genotype 1 form of the infection, the most common type, in combination with pegylated interferon and another pill called ribavirin. The Foster City, California-based company, the world’s biggest maker of AIDS drugs, hopes to gain approval for an all-oral combination that omits interferon for those patients within about a year. Gilead also is seeking sofosbuvir approval in other genotypes with and without interferon.

Sofosbuvir may generate $1.82 billion in sales next year, according to the average of nine analysts’ estimates compiled by Bloomberg. The drug can shrink the current treatment time to 12 weeks from about a year for most patients.

The panel voted 15-0 that sofosbuvir should be approved in combination with pegylated interferon and ribavirin for genotype 1 and genotype 4 patients who haven’t previously been treated. About 70 percent of patients in the U.S. have genotype 1.

Different Patients

The panel also voted 15-0 that the treatment in combination with only ribavirin should be cleared for genotype 2 and genotype 3 patients, which include as much as 25 percent of those with hepatitis C in the U.S. The combination for these patients would be the first all-oral regimen.

Gilead shares fell less than 1 percent to $69.68 at the close in New York.

“There were already high expectations going into the panel and the stock was at its all-time high yesterday already,” said Michael Yee, an analyst at RBC Capital Markets.

The panel today offered glowing reviews of sofosbuvir and discussed a question asked by the FDA about whether patients with genotype 1 hepatitis C who tried other treatments should have access to the drug as well, Yee said in an e-mail. Gilead only studied the treatment in genotype 1 patients who had never been treated before.

‘Important’ Therapy

“As we reviewed this application we realized how important a drug this was and we also realized that not every patient population was represented,” Debra Birnkrant, director of FDA’s Division of Antiviral Products, said during the meeting.

FDA modeled data to hypothesize whether the drug could be used in treatment-experienced patients.

Advisers voted 19-0 yesterday that a Johnson & Johnson (JNJ) and Medivir AB (MVIRB) hepatitis C medicine known as simeprevir should be approved for genotype 1 patients in combination with pegylated interferon and ribavirin. The drug can reduce current treatment time in half to 24 weeks. Potential simeprevir users need screening for a genetic mutation that renders the drug ineffective.

Analysts assumed treatment-experienced patients would use J&J and Medivir’s drug though Gilead now may be available for those patients, Yee said. He estimates sales of Gilead’s sofosbuvir will total $300 million in the first quarter of next year versus a consensus estimate of $223 million.

For the majority of current patients interferon and ribavirin are combined with Merck & Co.’s Victrelis or Vertex Pharmaceuticals Inc. (VRTX)’s Incivek. Victrelis, Incivek and J&J’s simeprevir are protease inhibitors that battle genotype 1 hepatitis C. Sofosbuvir, if approved, will be the first in a new class of drugs called nucleotide polymerase inhibitors.

Treatment-experienced patients made up 40 percent of first-year sales of Victrelis and Incivek, Yee said. Sales of the two drugs totaled $1 billion in 2011, the year they came on the market, and $1.7 billion last year, according to data compiled by Bloomberg.

To contact the reporter on this story: Anna Edney in Washington at aedney@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

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FDA Issues Revised Draft Guidance on Hepatitis C Drug Development

You are receiving this message as a subscriber to the FDA hepatitis electronic list serve. The purpose of the list serve is to relay important information about viral hepatitis-related products and issues, including product approvals, significant labeling changes, safety warnings, notices of upcoming public meetings and alerts to proposed regulatory guidances for comment.

Please do not reply to this message.

The Food and Drug Administration (FDA) has published draft guidance to assist sponsors in the clinical development of direct-acting antiviral (DAA) drugs for the treatment of chronic hepatitis C (CHC) from the initial pre­-investigational new drug application (pre-IND) through the new drug application (NDA) and postmarketing stages.

You can read the draft guidance at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM225333.pdf

Although comments on guidance may be submitted at any time, to ensure that the Agency considers your comment on this draft guidance before it begins work on the final version of the guidance, please  submit either electronic or written comments on the draft guidance by December 23, 2013.

Comments may be submitted electronically at http://www.regulations.gov. Alternatively, written comments can be submitted to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.

This guidance revises the draft guidance for industry entitled “Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Agents for Treatment” issued in September 2010. Significant changes in this revision include:

• Details on phase 2 and phase 3 trial design options for the evaluation of interferon (IFN)-free and IFN-containing regimens in treatment-naïve and treatment-experienced populations, including DAA-experienced populations.
• Revised primary endpoint to sustained virologic response at 12 weeks post-treatment cessation.
• Greater emphasis on DAA drug development in special populations including trial design options for human immunodeficiency virus/hepatitis C virus co-infected patients, patients with decompensated cirrhosis, and patients pre- or post-liver transplant.
• More details on clinical virology considerations for DAA drugs.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration

FDA has created a Patient Network web site, designed from the ground up for patients and patient advocates. It provides information on what FDA does, and various topics of interest to patients, including opportunities to comment on a variety of regulatory issues like this one.

A New Day

Hopkins Medicine Magazine Fall 2013

The new therapies are arriving at a crucial time, says Mark Sulkowski. “We’re just now getting into the peak of the impact of hepatitis C in the United States.”

Date: October 1, 2013

One day in late 1995, David Frick began to suffer severe abdominal pain. A few months earlier, he had completed a PhD in biology at Johns Hopkins, and now he was doing a postdoctoral research fellowship on the Homewood campus, studying bacterial enzymes. When the pain hit, his first assumption was that it was appendicitis. He’d go under the knife, be away from his lab bench for a week or so, and then life would return to normal.

Or so he thought. A few days later, the diagnosis arrived: Frick had hepatitis C. He had probably acquired the virus from a contaminated blood product shortly after he was born, when he received transfusions to treat a rare disorder. After 20-odd years of silent destruction, the virus had caused extensive cirrhosis in his liver. He would need a transplant.

Two years later in Boston, where he was doing a postdoc at Harvard, Frick’s liver went into severe failure, and he received his transplant. It was a grueling experience, with long weeks in a hospital bed. “But the transplant year wasn’t the worst year of my life,” Frick says today. “The worst year of my life was the following year, when I went through the treatment for hepatitis C.”

After his transplant Frick needed to try to eradicate the virus from his body, so that hepatitis C wouldn’t ruin his second liver. That meant taking what was, in the late 1990s, the cutting-edge therapy for hepatitis C: 48 weeks of injections with interferon-alfa, a synthetic version of one of the body’s common antiviral proteins. Interferon-alfa carries brutal side effects: fevers, sweats, chills, depression, fatigue. “It felt like I had the flu for nearly an entire year,” Frick says. “I’m glad I did it—I’ve been perfectly fine ever since. But that was very, very tough.”

Frick, who now studies the hepatitis C virus (HCV) at the University of Wisconsin-Milwaukee, vowed to devote the rest of his career to hepatitis C until a more effective and tolerable cure was discovered. That moment appears finally to have arrived—thanks in part to decades of effort by Johns Hopkins researchers.

In the last three years, several new classes of drugs have emerged that directly target enzymes specific to the hepatitis C virus. As early as December 2013, the FDA might approve the first-ever interferon-free therapy for certain hepatitis C patients. Within a few years, says Mark Sulkowski, medical director of the Viral Hepatitis Clinic at Johns Hopkins, the standard treatment for hepatitis C might be just 12 weeks long—or even eight—and involve no interferon. Even better, the new medications appear to be effective for almost everyone, whereas roughly 50 percent of patients have failed to respond to interferon-alfa.

“These have truly been breakthroughs,” says Sulkowski. “The treatment stands to become dramatically simpler, more effective, and easier to tolerate.” Sulkowski has waited a long time to see these victories. For nearly two decades, he has directed clinical trials of hepatitis C medications at Hopkins. While most of those drugs have been brewed in pharmaceutical companies’ private labs, Hopkins researchers have played a central role in testing their safety and efficacy, especially among vulnerable populations such as people co-infected with HIV and HCV.

The new therapies are arriving at a crucial moment, Sulkowski adds. “We’re just now getting into the peak of the impact of hepatitis C in the United States,” he says. Millions of baby boomers are believed to have been exposed to the virus via intravenous drug use, tattooing, and contaminated blood transfusions between 1965 and 1990. (Blood products have been screened for the virus since 1992, so transfusion is no longer a danger.)  Because it takes decades for the virus to do its silent damage to the liver, the national rates of cirrhosis and liver cancer have only recently begun to spike upward. Each year since 2007, hepatitis C has been estimated to kill more Americans than HIV; liver cancer is one of the few types of cancer with a rising mortality rate.

“People say, [the virus] has a very slow progression rate,” Sulkowski says. “And that’s true. It takes decades to progress. But the peak infections in the U.S. occurred 30 or 40 years ago. So, now we’ve reached the time when many people are progressing. This is a major issue right now.”

When david frick received his blood transfusions as an infant in the late 1960s, hepatitis C was an unknown concept. The year 1974 saw the first scientific publication about transfusion-related liver infections that were not caused by the familiar hepatitis A or hepatitis B viruses. But it took another decade and a half until the viral pathogen behind what was then known as “non-A-non-B hepatitis” was finally found. In April 1989, a pair of papers in Science announced the discovery and basic structure of the hepatitis C virus.

A year later, a young physician named David L. Thomas began a fellowship in infectious diseases at Johns Hopkins. Early in his fellowship, he was asked to lead a journal club discussion of the 1989 Science papers. He has been hooked on hepatitis C ever since. “It was a cutting-edge topic,” says Thomas, who is now director of the Division of Infectious Diseases at Hopkins. “But it wasn’t immediately clear what a significant public health challenge hepatitis C would turn out to be.”

Thomas, perhaps more than any other single scientist, helped alert the world to the severity of the hepatitis C problem. “We knew that it was a transfusion issue,” he says. “So it was natural to ask whether the virus could also be transmitted through other blood vectors.”

Sadly, the answer turned out to be yes. Throughout the 1990s, Thomas worked with Hopkins colleagues at the schools of Medicine and Public Health to document the alarmingly high rates of hepatitis C infection among IV drug users in Baltimore and other sites around the world. The team also studied sexual transmission (which turned out not to be a major vector), transmission during childbirth, and needle stick injuries among Johns Hopkins Hospital employees.

Those early needle stick studies became a vital source of information about the virus’s life cycle: Because Thomas and his colleagues knew almost the exact time of transmission, they could draw blood samples from the employees daily to learn how the virus evaded the human immune system during the acute phase of infection.

The studies also allowed Hopkins researchers to examine the mechanisms that allow a lucky minority of people—roughly 20 to 30 percent—to clear the virus from their systems without developing chronic infections. That line of research, which was led by Chloe Thio, an associate professor of medicine, and Priya Duggal, a geneticist at the Bloomberg School of Public Health, has helped lay the groundwork for potential vaccines.

After several years of study, a basic epidemiological portrait emerged. After exposure to the virus, between 70 and 80 percent of patients develop chronic infections. (More than 150 million people internationally, including 3.2 million in the United States, are now estimated to have chronic hepatitis C.) Of those chronic infections, between 15 and 30 percent will eventually cause liver cirrhosis, though that process can take as long as 30 years. And among hepatitis C patients who progress to cirrhosis, between 1 and 3 percent each year will develop liver cancer.

“The most alarming thing is that roughly half of the people with chronic hepatitis C in the United States have not been diagnosed,” says Scott Holmberg, chief of the epidemiology and surveillance branch of the viral hepatitis center at the Centers for Disease Control, which recently recommended that all Americans born between 1945 and 1965 be screened for the virus. “And among those who have been diagnosed, only a relatively small proportion have been treated, in part because the treatments have been so difficult to take.”

That will soon change. While his Hopkins colleagues have analyzed the virus and traced the vectors of public infection, Sulkowski has spent years leading clinical trials of potential new treatments. He has seen firsthand the side effects that made David Frick’s year of treatment so miserable. But in the last two years, Sulkowski’s team has led trials of drugs that appear to radically change the nature of treatment for hepatitis C.

“The cornerstone of hepatitis C treatment since the late 1990s has been interferon-alfa and ribavirin, a regimen that carries severe side effects,” Sulkowski says. “So what we have had, in effect, is a treatment that’s effective for many people, but toxic. And the special challenge is that hepatitis C is an asymptomatic disease, right up to the time your liver has already sustained severe damage.”

“It can be hard for people to wrap their heads around the idea that they have a potentially fatal illness,” Sulkowski continues. “They feel fine, and now you’re asking them to take medications that will make them feel sick for a year.”

In the last five years, however, several new drugs have emerged that promise radical improvements on the traditional regimen. In 2011, the FDA approved two medications—boceprevir and telaprevir—that target one of the virus’s protease enzymes, much as the cornerstone medications for HIV target that virus’s protease. Taken in combination with interferon and ribavirin, those medications have dramatically improved the proportion of patients who can completely clear the virus from their systems, from roughly 40 percent to roughly 75 percent, according to Sulkowski. But they have only added to the traditional therapy’s burden of side effects.

It is the next generation of medications that most excites Sulkowski, because they promise to do away entirely with interferon injections and ribavirin. These medications target the virus’s polymerase enzyme, which helps to assemble new strands of RNA when the virus replicates, as well as a viral protein known as NS5A. In recent clinical trials, a pair of these new agents—sofosbuvir, a polymerase inhibitor, and declatasvir, an NS5A inhibitor—have demonstrated the ability to clear the virus in almost 100 percent of patients, and they appear to be far better tolerated than the traditional therapies. Sofosbuvir was submitted to the FDA for approval this summer, with a decision expected in December.

“The flu-like symptoms of interferon are gone,” Sulkowski says. “The severe fatigue is gone. Anemia, which has been a consequence of the first protease inhibitors, is no longer a major issue. And the treatment duration has been reduced to, in some cases, 12 weeks, down from 24.”

Because the medications in the pipeline appear so promising, many physicians are urging their patients to defer treatment unless they already show signs of significant liver fibrosis. “I’m encouraging my patients to wait until the new medications come on line,” Thomas says.

“I wouldn’t take any of the old stuff,” says Lynda Dee, a Baltimore attorney who tested positive for hepatitis C several years ago. From firsthand observation of friends and acquaintances, she drew her own conclusion: “Interferon-alfa and ribavirin are a nightmare.” 

Since early tests showed that her liver had not been severely damaged, Dee decided to wait for better treatments to emerge. When she learned last year about the opportunity to participate in a clinical trial of the new antiviral drugs, she chose to sign on. “There’s always a lot of angst associated with something like that,” she says. “But it seems to have worked beautifully.”

Andrew Cameron, who directs the liver transplant program at Hopkins, also sees great promise in the new medications. Among hepatitis C patients whose livers have already deteriorated so badly that they require transplantation, the traditional therapies have usually done poorly, both before and after transplant, Cameron says. People with end-stage liver disease are especially intolerant of interferon’s side effects.

“If we can use easy-to-tolerate drugs to clear the virus or reduce the viral load before surgery, that will make a huge difference,” Cameron says. Among other things, it will broaden the range of livers available to hepatitis C patients. Traditionally, these patients have been restricted to livers from donors younger than 50 or 55, because (for reasons not well understood) the hepatitis C virus tends to roar back and quickly destroy livers from older donors. Since roughly half the transplant pool is from donors older than 55, this has been a major burden for hepatitis C patients. “We might soon be able to open up the entire range of donors to hepatitis C cases,” Cameron says. “That’s very, very exciting.”

Alongside their excitement, hepatitis researchers like Sulkowski also raise four notes of caution about the new wave of medications. One is that the drugs have not been thoroughly tested so far on some of the most medically vulnerable populations, including people who carry both HIV and HCV and those with advanced liver disease. (Clinical trials in that group are presently under way, and Sulkowski says that the early findings are promising.)

A second concern: It’s not known yet whether viral resistance will emerge as these drugs are used in real-world settings. “That’s a question that I don’t think we have much data for yet,” says Susanna Naggie, a Duke University scientist who earned her MD at Hopkins in 2002. “But the early signs are that it probably will matter. Some recent data suggested that of the people who have failed treatment on [the protease inhibitors approved in 2011], half of them have protease-related mutations in the virus.” The solution, Naggie says, will probably be to use combinations of drugs from different classes, as is done in HIV therapy.

Third, scientists hope that the apparent success of the new drugs will not slow down funding of vaccine development for hepatitis C. Andrea Cox, an associate professor at Hopkins, is currently conducting a clinical trial of a potential vaccine [see sidebar].

Finally, researchers foresee difficult conflicts ahead about how many people should be offered the new medications, which are expected to carry a price tag of tens of thousands of dollars, at least initially. Should the drugs be given to the millions of people who are HCV-positive, or only to those who have already suffered actual liver damage? Should some patients be asked to wait until the drugs get cheaper? “I don’t know of any precedent for this kind of thing in the history of medicine,” says Hopkins virologist Stuart Ray. “This won’t be an easy ethical decision.” Recall that only 15 to 30 percent of chronic hepatitis C infections are estimated to result in full-blown liver cirrhosis. If you’re an HCV-positive individual, you might understandably feel that it’s worth $70,000 to reduce that risk to zero. But will private insurance companies and Medicare agree?

Even with all of those cautions in mind, these scientists seem palpably joyous about the imminent transformation of hepatitis C therapy.  “It was completely unimaginable a decade ago, or even two years ago, that we would have these kinds of treatment advances,” Sulkowski says. “Soon we’ll be able to tell patients that they’ll only have to take one pill, once or twice a day, for 12 weeks.”

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Canada falling behind in tackling hepatitis C

Hepatitis C symposium highlights need for national action plan

Toronto, ON (October 25, 2013) – Today, international researchers will present a compelling case for government action on hepatitis C. The disease can now effectively be screened, diagnosed, treated and often cured. Unfortunately, progress has hit a critical moment; in order to prevent thousands of unnecessary deaths and to avoid soaring acute care costs, Canada needs a national action plan to identify, treat and cure more patients with hepatitis C.

“We have the knowledge, the diagnostic tests and an ever-improving crop of therapies that we can use to treat patients,” says Dr. Morris Sherman, chairman of the Canadian Liver Foundation. “However, our ability to help people is hampered by our lack of resources. We have to find innovative and affordable ways to bring advancements to patients; otherwise we will waste the efforts of researchers in Canada and around the world.”

During Hepatitis C Virus: From Discovery to Cure, a symposium jointly presented by the Gairdner Foundation and the Canadian Liver Foundation, Dr. Harvey Alter and Dr. Daniel Bradley, both winners of the prestigious 2013 Canada Gairdner International Award, will recount their ground-breaking work in isolating and identifying the hepatitis C virus. This research led to the development of the first screening tests for the virus.

Leading Canadian and American specialists will join Dr. Alter and Dr. Bradley, highlighting the ongoing challenges in measuring the current and future burden of hepatitis C and in overcoming the social, financial and administrative barriers standing between patients and the care they need.

“It’s incredible how far we’ve come and how much we’ve learned in the last 20 years,” says Dr. Gary Levy, former director of the Multi-Organ Transplant Program at the University Health Network in Toronto and one of the organizers of the symposium. “Hepatitis C is the leading cause of liver transplantation in this country, but with advances in treatment it doesn’t have to be. Transplants are, and always should be, a last resort, but we are often left with no choice because patients already have advanced forms of the disease by the time they are diagnosed. We should be using what we know to identify patients and intervene long beforehand.”

At Toronto General Hospital, which has the largest transplant program in the country, about 35 per cent of liver transplants performed each year are for patients living with hepatitis C.

Sergeant Lance Gibson was diagnosed with hepatitis C in January 2009 and discovered he had been living with the virus for 28 years after receiving blood products as a teenager. While in the process of being released from the Canadian Armed Forces (CAF), his medical examination revealed that he had the disease. As a result, he had to turn down a lucrative civilian position and stay in the CAF for treatment. He received a liver transplant in May 2012.

“While I’m grateful to the donor and the doctors who saved my life, I don’t think that liver transplants should be the answer,” says Lance. “If doctors were routinely testing for hepatitis C, mine might have been identified much earlier and I might have had more options for treatment.”

Canada needs a national action plan for hepatitis C

Earlier this year, the Canadian Liver Foundation’s report – Liver Disease in Canada: A Crisis in the Making – highlighted the gaps in knowledge, care and resources for all forms of liver disease. For hepatitis C, the report called for widespread screening of adults born between 1945 and 1975. This recommendation was supported by Canadian specialists in a recently published Canadian Medical Association Journal (CMAJ) article1. The report also recommended changes to how hepatitis care is funded and managed as well as how patients qualify for treatment reimbursement.

“We estimate that only two per cent of the more than 300,000 Canadians living with hepatitis C have undergone treatment,” says Dr. Sherman. “We recognize the financial implications of diagnosing and treating each Canadian with the disease, but if we don’t figure out a strategy now, we will end up spending even more in acute care costs or resorting to transplants to save the lives of patients that could have otherwise been cured.”

About the Canadian Liver Foundation
Founded in 1969 by a group of doctors and business leaders concerned about the increasing incidence of liver disease, the CLF was the first organization in the world devoted to providing support for research and education into the causes, diagnoses, prevention and treatment of all liver disease. Through its chapters across the country, the CLF strives to promote liver health, improve public awareness and understanding of liver disease, raise funds for research and provide support to individuals affected by liver disease.

Media contact:
Melanie Kearns
416-491-3353 x4923
mkearns@liver.ca

Additional resources:
B-roll is available for download here.

Canadian Liver Foundation’s Report, Liver Disease: A Crisis in the Making can be accessed here.

Canadian Liver Foundation’s Position Statement on Hepatitis C Testing can be accessed here.

References:
1 Canadian Medical Association Journal. A Canadian screening program for hepatitis C: Is now the time? H. Shah, J. Heathcote, J. Feld http://www.cmaj.ca/content/early/2013/09/30/cmaj.121872.extract

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FDA Panel Backs Sofosbuvir for Hepatitis C– (Excellent breakdown of the studies presented) – From Medscape

Troy Brown, RN
October 25, 2013

An advisory committee to the US Food and Drug Administration (FDA) voted unanimously (15-0) to recommend sofosbuvir (Gilead Sciences, Inc) in combination with ribavirin for the treatment of adults with chronic hepatitis C virus (HCV) genotypes (GT) 2 and 3 infections.

The committee also recommended (15-0) sofosbuvir in combination with pegylated interferon and ribavirin for treatment of chronic HCV in treatment-naïve adults with GT 1 and 4 infections.

Sofosbuvir is an NS5B polymerase inhibitor and the first drug in this class to be reviewed in the US. It is intended to be administered as a 400-mg oral dose once daily in combination with other drugs. The approval is momentous because it provides the first interferon-free regimen for adult patients with HCV GTs 2 and 3.

"This is a tremendous advance for patients, and I think both the sponsor and the FDA should be applauded for having gotten us here," said voting member Elizabeth Connick, MD, a professor of medicine at University of Colorado Denver, Division of Infectious Diseases, in Aurora, Colorado.

The vote follows a discussion of 4 pivotal phase 3 trials:

In patients with HCV GT 2 or 3:

· P7977-1231 (FISSION) evaluated sofosbuvir + ribavirin (SOF + RBV) treatment for 12 weeks in treatment-naïve patients (499 patients: 256 in the SOF + RBV group; 243 in a pegylated interferon + ribavirin [PEG + RBV] group);

· GS-US-334-0107 (POSITRON) evaluated SOF + RBV for 12 weeks in patients who were interferon intolerant, ineligible, or unwilling to take interferon (278 patients: 207 in the SOF + RBV group; 71 in the placebo group);

· GS-US-334-0108 (FUSION) evaluated SOF+RBV for 12 or 16 weeks in treatment-experienced patients (201 patients: 103 in the SOF+RBV 12-week group; 98 in the SOF+RBV 16-week group).

In patients with HCV GT 1, 4, 5, or 6:

· GS-US-334-0110 (NEUTRINO), evaluated SOF (400 mg once daily) + PEG (180 μg/week) + RBV (1000 or 1200 mg/day) for 12 weeks in treatment-naïve patients (N = 327).

Efficacy

For all 4 trials, the primary endpoint was sustained virologic response (SVR), defined as HCV RNA less than the lower limit of quantification (LLOQ) 12 weeks after stopping active treatment (SVR12).

FISSION

In FISSION, the overall SVR12 rate was 67% for both groups. When they looked at the subgroups (by genotype) of the SOF+ RBV group, the SVR12 rate was 95% in the subgroup of HCV genotype 2 subjects, and 56% in the subgroup of genotype 3 subjects.

In the PEG + RBV group, SVR12 rates were 78% in those with HCV GT2 and 63% in those with HCV GT3.

POSITRON

In POSITRON, the overall SVR12 rate was 78% in the SOF + RBV group and 0% in the placebo group. In the SOF + RBV group, SVR12 rates were 93% in those with HCV GT2 and 61% in those with HCV GT3.

Relapse was the reason for most treatment failures (HCV GT3, 38%; HCV GT2, 5%). No patients in the placebo group achieved SVR.

FUSION

In FUSION, the SVR12 rate was higher in the SOF + RBV16 week group (71%) than the SOF + RBV12 week group (50%). Each of these was significantly higher ( P < .001), when compared with the null rate of 25%. When treatment duration was increased by 4 weeks in the 12-week group, SVR12 rates in those with HCV GT2 increased from 82% to 89%, and in those with HCV GT3, SVR12 rates increased from 30% to 62%.

NEUTRINO

In NEUTRINO, overall, SVR12 was achieved by 90% of subjects compared with a historical SVR12 rate of 60%, and this was statistically significant (P < .0001). The overall relapse rate was 9%.

The SVR12 rate in those with GT1 (N = 292) was 89% (GT1a-92%; GT1b 82%). In those with GT4 (N = 28) the SVR12 rate was 96%. Too few subjects with GT5 and GT6 were in the clinical trial to allow for definitive dosing recommendations for those groups.

Safety

No serious or severe cardiac adverse events occurred in sofosbuvir-treated patients, and no treatment discontinuations occurred due to cardiac adverse events. Palpitations were the only Grade 2 event found in the SOF + RBV group. Eleven patients in the SOF + RBV group experienced Grade 1 events including palpitations, tachycardia, sinus bradycardia, extrasystoles, and ventricular extrasystoles.

"It's a great step forward," noted voting member Lawrence S. Friedman, MD, chair of the department of medicine at Newton-Wellesley Hospital, Massachusetts, assistant chief of medicine at Massachusetts General Hospital, a professor of medicine at Harvard Medical School, and a professor of medicine at Tufts University School of Medicine, in Boston.

"I was particularly impressed by the very favorable resistance data," said voting member Russell B. Van Dyke, MD, a professor of clinical pediatrics and head of the Section of Pediatric Infectious Diseases at Tulane University School of Medicine, New Orleans, Louisiana.

The committee was largely supportive of offering sofosbuvir in combination with pegylated interferon and ribavirin to adults with GT1 infection who are nonresponders to a previous course of pegylated interferon and ribavirin. Several members would like to see additional studies including those on long-term effects of treatment and management of complex patients.

The FDA is expected to make a decision by December 8.

The advisory committee members reported no relevant financial relationships.

US Food and Drug Administration (FDA) Antiviral Drugs Advisory Committee meeting October 25, 2013. FDA Briefing, Gilead Briefing

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Panel recommends FDA approve sofosbuvir for hepatitis C – (Excellent summary from Healio)

Provided by Healio

October 25, 2013

The FDA’s Antiviral Drugs Advisory Committee today recommended approval of sofosbuvir, a first-in-class, once-daily oral nucleotide inhibitor from Gilead Sciences, for treatment of chronic hepatitis C virus genotypes 1, 2, 3 and 4.

The panel voted unanimously and enthusiastically in support of approving sofosbuvir in combination with ribavirin for treatment of HCV GT 2 and 3 in adult patients.

“This is a game-changer,” committee member Marc G. Ghany, MD, MHSc, staff physician with the liver diseases branch of the National Institute of Diabetes and Digestive and Kidney Diseases, said.

The panel also voted 15-0 but offered more reservations in support of approving sofosbuvir in combination with pegylated interferon and ribavirin (PR) for treatment of HCV GT 1 and 4 in treatment-naive patients.

“I was hesitant to give approval for a one-arm study,” committee member Dean Follmann, PhD, chief, biostatistics research branch, National Institute of Allergy and Infectious Diseases, said. “The 90% success rate is what really made me comfortable with this.”

The votes followed a discussion on a series of phase 3 studies of a sofosbuvir-based regimen, generally of 12 to 16 weeks, that demonstrated similar or superior effectiveness to current treatment options at primary endpoint of sustained virologic response (SVR) at 12 weeks.

The committee also discussed, but did not vote, on whether evidence supported sofosbuvir in combination with PR for treatment of chronic hepatitis C in patients with GT 1 infection who are nonresponders to a prior course of PR.

Studies did not directly analyze this patient population, but the FDA presented extrapolated data that suggested about 75% of treatment-experienced patients might respond positively to the therapy.

Several committee members expressed concern over the lack of real data, while others suggested it was a risk worth taking.

Thomas P. Giordano, MD, MPH, associate professor of medicine at Baylor College of Medicine, questioned whether voicing approval was appropriate.

“Clinicians are going to do what they have to do to take care of their patients, but the agency’s responsibility is at a different level,” he said.

On the discussion of whether evidence supported use of sofosbuvir in combination with ribavirin in hepatocellular carcinoma patients meeting Milan criteria awaiting liver transplantation, panel Chairman Yoshihiko Murata, MD, PhD, division of infectious diseases, University of Rochester School of Medicine and Dentistry, said there was a consensus among the panel on the need to treat this population.

“It’s work in progress, but it’s work that has to be done,” Donald J. Alcendor, PhD, associate professor, department of microbiology  and immunology at Meharry Medical College, said.

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Hepatitis C: CHMP Backs 'Compassionate Use' of Sofosbuvir

International Approvals > Medscape Medical News

Miriam E. Tucker

October 25, 2013

The European Medicines Agency's (EMA's) Committee for Medicinal Products for Human Use (CHMP) has issued a "compassionate use" opinion for Gilead Sciences Inc's antiviral drug sofosbuvir in patients who have chronic hepatitis C virus (HCV) infection and who are awaiting a liver transplant or have already received one.

This is the third time the CHMP has used the compassionate use designation for a drug. Set up at the national level, compassionate use programs aim to give patients with life-threatening, chronic, or seriously disabling disease who do not have other treatment options access to drugs that are still under development or consideration and that have not yet been authorized for wider use.

Sofosbuvir, an NS5B polymerase inhibitor, is currently under evaluation by the EMA for wider use in patients with chronic HCV. In the meantime, Sweden had requested a CHMP opinion for use of the antiviral in combination with other agents specifically in patients before or after liver transplantation.

In the United States, sofosbuvir is being discussed today at a US Food and Drug Administration advisory committee hearing for the treatment of chronic HCV infection in combination with other agents in adult patients with genotypes 1 to 6 and/or adult patients awaiting liver transplantation.

HCV infection occurs in 0.4% to 3.5% of the population in different EU member states and is the most common single cause of liver transplantation in the European Union. There is currently no standard therapy for patients with chronic HCV who are awaiting transplantation or who have already received a liver transplant, and there are no approved treatments for most of these patients.

"Many patients with HCV infection in the pre- and post-transplant setting are therefore in urgent medical need of therapy to prevent graft reinfection or to treat recurrent HCV infection in the graft," the EMA said in a statement.

The CHMP opinion is intended to ensure a common approach for member states that are considering setting up a compassionate use program. It is not mandatory. An assessment report and conditions of use of sofosbuvir in this setting will be published shortly on the agency's Web site, the EMA says.

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Also See: European Medicines Agency advises on compassionate use of sofosbuvir

FDA Advisory Committee Supports Approval of Gilead's Sofosbuvir for Chronic Hepatitis C Infection

- Final FDA Decision on Sofosbuvir Anticipated by December 8, 2013 -

FOSTER CITY, Calif., Oct 25, 2013 (BUSINESS WIRE) -- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the Antiviral Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) has voted unanimously (15-0) that the available data support approval of the once-daily nucleotide analogue sofosbuvir in combination with ribavirin for the treatment of chronic hepatitis C in adult patients with genotype 2 and 3 infection. Committee members also voted unanimously (15-0) that the available data support approval of sofosbuvir in combination with pegylated interferon and ribavirin for the treatment of chronic hepatitis C in treatment-naive adult patients with genotype 1 and 4 infection.

The recommendations of the Advisory Committee are not binding, but will be considered by FDA as the agency completes its review of Gilead's New Drug Application (NDA) for sofosbuvir. Gilead submitted the NDA on April 8, 2013 and was granted a priority review. The FDA also granted sofosbuvir a Breakthrough Therapy designation. The FDA grants Breakthrough Therapy designation and priority review status to drug candidates that may offer major advances in treatment over existing options. A target review date of December 8, 2013 has been set under the Prescription Drug User Fee Act (PDUFA). Applications for marketing approval of sofosbuvir are also pending in the European Union, Australia, Canada, New Zealand, Switzerland and Turkey.

The sofosbuvir NDA is supported primarily by data from four Phase 3 studies, NEUTRINO, FISSION, POSITRON and FUSION, in which 12 or 16 weeks of sofosbuvir-based therapy was found to be superior or non-inferior to currently available treatment options or historical controls, based on the proportion of patients who had a sustained virologic response (HCV undetectable) 12 weeks after completing therapy (SVR12). During the review, data from an additional Phase 3 study, VALENCE, were filed to the NDA. In this study, patients with genotype 3 HCV infection were treated with sofosbuvir and ribavirin for 24 weeks. Patients who achieve SVR12 are considered cured of HCV.

About Sofosbuvir

Sofosbuvir is a nucleotide analogue inhibitor of the HCV NS5B polymerase enzyme, which plays an essential role in HCV replication. Sofosbuvir is a direct-acting agent, meaning that it interferes directly with the HCV life cycle by suppressing viral replication. Sofosbuvir is an investigational product and its safety and efficacy have not been established.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North and South America, Europe and Asia Pacific.

Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that FDA, EMA and other regulatory agencies may not approve sofosbuvir in the currently anticipated timelines or at all, and that any marketing approvals, if granted, may have significant limitations on their use. In addition, future studies of sofosbuvir, including in combination with other products, may not produce favorable results. Further, even if approved, Gilead may not be able to successfully commercialize sofosbuvir, and may make a strategic decision to discontinue its development if, for example, the market for the product fails to materialize as expected. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in Gilead's Quarterly Report on Form 10-Q for the quarter ended June 30, 2013, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

For more information on Gilead Sciences, please visit the company's website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

Source: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Patrick O’Brien, 650-522-1936 (Investors)
Cara Miller, 650-522-1616 (Media)

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Gilead sweeps FDA panel vote for pioneering hep C drug sofosbuvir

Provided by FierceBiotech

October 25, 2013 | By John Carroll

There were no big surprises for Gilead's $11 billion hepatitis C drug sofosbuvir at today's FDA panel review. The therapy, which promises to help create an entirely new standard of care for the millions of people afflicted with the virus, won a clear endorsement from agency experts. And now it's likely headed for a near-term approval as the FDA formally considers the application.

The panel voted unanimously that the drug and various combinations should be approved for all four basic genotypes. Sofosbuvir was endorsed in combination with ribavirin for genotypes 2 and 3, and in genotypes 1 and 4 in combination with ribavirin as well as in combination with interferon for treatment-naive patients.

The agency already signaled its views in an internal review released earlier this week which heralded the therapy as the first interferon-free drug that clearly demonstrated its efficacy and safety among important groups of hep C patients.

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FDA panel unanimously backs Gilead's hepatitis C drug sofosbuvir

WASHINGTON | Sat Oct 26, 2013 12:25am IST

WASHINGTON (Reuters) - A federal advisory panel recommended on Friday that U.S. health regulators approve Gilead Sciences Inc's experimental hepatitis C drug sofosbuvir.

The panel voted 15 to 0 in favor of approval of the drug in patients with two variants of the liver-damaging disease - genotype 2 and genotype 3 - in combination with an existing treatment, ribavirin.

If approved, it would be the first all-oral treatment for genotypes 2 and 3.

The panel also voted unanimously to approve the drug in patients with genotype 1 and genotype 4 variants in combination with ribavirin and the injectible drug interferon in patients who have not received prior therapy.

Genotype 1 accounts for roughly 70 percent of hepatitis C cases. The FDA is not bound to follow the advice of its panels but typically does so.

(Reporting by Toni Clarke in Washington; Editing by Gerald E. McCormick)

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