April 24, 2013

HCV Treatment — No More Room for Interferonologists?

EDITORIAL

Joost P.H. Drenth, M.D., Ph.D.

April 23, 2013DOI: 10.1056/NEJMe1303818

The landscape of therapy for hepatitis C virus (HCV) infection is changing rapidly. Until recently, the standard of care for HCV infection was a combination of peginterferon and ribavirin. Our increased understanding of the basic biology of HCV led to the identification of specific proteins involved in the replication of the virus. These proteins can be targeted by protease and polymerase inhibitors.

Two years ago, the advent of protease inhibitors, such as telaprevir and boceprevir, profoundly affected the field.1,2 These agents improved the likelihood of cure but came with a number of inherent limitations. Protease inhibitors do not have antiviral activity in HCV genotypes other than the predominant genotype 1, which leaves at least five other HCV genotypes without coverage. Moreover, protease inhibitors can promote viral resistance, which usually signals therapeutic failure, and have multiple pharmacokinetic interactions with other drugs. Finally, protease inhibitors need to be administered with peginterferon and ribavirin, two drugs with extensive and well-established side-effect profiles that are aggravated by the addition of telaprevir or boceprevir.

Clinicians who treat patients with HCV infection have learned to accept and treat adverse effects as an integral part of patient care, but the inclusion of protease inhibitors in the therapeutic arsenal has added a layer of complexity. Indeed, the major challenge of contemporary interferon therapy is adequate management of side effects. Physicians and patients are ready for less toxic therapeutic options.

Two groups of investigators (Jacobson et al.3 and Lawitz et al.4) now suggest in the Journal that change is about to happen. They describe the use of sofosbuvir, a novel polymerase inhibitor, in a series of four experimental studies targeting patients with HCV infection. In three randomized trials — FISSION, POSITRON, and FUSION — investigators focused on patients with HCV genotype 2 or 3, as seen in everyday clinical practice, including patients who had received no previous treatment, those who were unwilling to take interferon or had unacceptable side effects, and those who did not have a response to previous therapy. All the studies had a similar end point: a sustained virologic response at 12 weeks after the end of therapy. In addition, in the single-group, open-label NEUTRINO study, investigators studied the use of a sofosbuvir-based regimen in patients with genotype 1, 4, 5, or 6 infection.

The FISSION study examined the efficacy of 12 weeks of sofosbuvir plus ribavirin, as compared with the standard of care, peginterferon alfa-2a plus ribavirin, administered for 24 weeks. Standard therapy was successful in 78% of patients with genotype 2 infection and 63% of those with genotype 3 infection, as compared with rates of 97% and 56%, respectively, with the sofosbuvir-based regimen.

The POSITRON study evaluated a population that was not deemed to be eligible for interferon-based therapy and compared 12 weeks of sofosbuvir plus ribavirin with placebo. The primary reasons for ineligibility were a preexisting psychiatric disorder (57%) or autoimmune disorder (19%). None of the patients in the placebo group achieved the end point, but 93% of those with genotype 2 infection and 61% of those with genotype 3 infection had a sustained virologic response with sofosbuvir plus ribavirin.

The FUSION study, which targeted patients without a sustained response to interferon-based therapy, compared a 12-week regimen of sofosbuvir–ribavirin with a 16-week regimen. Four additional weeks of treatment made a difference, with an increase in the rate of sustained virologic response from 86% to 94% in patients with genotype 2 infection and from 30% to 62% in those with genotype 3 infection.

Finally, the investigators captured some evidence for the pangenotypic anti-HCV properties of sofosbuvir. In the NEUTRINO study, patients with genotype 1 infection (89%), genotype 4 infection (9%), or genotype 5 or 6 infection (2%) who received 12 weeks of treatment with a combination of sofosbuvir, peginterferon, and ribavirin had a collective rate of sustained virologic response of 90%.

The speed of development of drugs to treat HCV infection is unprecedented. The publication of clinical data with respect to sofosbuvir comes only 3 years after the publication of the chemical discovery of the compound.5 Although the data from the four trials discussed here are encouraging, the design of the trials may have suffered from the intense competition that drug companies face in this market. In the tower of evidence-based medicine, randomized clinical trials are superior to open-label studies. However, of the four studies that are discussed here, only three were randomized, and only one was placebo-controlled. In addition, the results for sofosbuvir in these studies falls short of the findings reported for the drug in an earlier study by Gane et al.,6 in which the rate of sustained virologic response was 100%. One of the reasons for the difference may be that the design of the study by Gane et al. was less rigorous than the designs of the studies discussed here. Also of note, the end point that was used in the four studies differed from that used in the study by Gane et al. The Food and Drug Administration only recently approved an end point of a sustained virologic response at 12 weeks (rather than the previously approved 24 weeks) as acceptable for HCV trials.7

Our current therapy for HCV infection revolves around side-effect management in patients receiving interferon, who require intense monitoring. Current therapies are typically offered in dedicated centers by physicians (aptly termed interferonologists) who are well versed in dealing with the toxic effects of interferon. Without alternatives to interferon therapy, we are pushing the envelope in the acceptance of risks to certain patients (e.g., those with a psychiatric history). The data from the sofosbuvir trials suggest that a radical change in clinical practice is imminent. But it may be premature to start dismantling the dedicated centers now that interferon is in retreat, since ribavirin is still part of the most successful interferon-free regimens. Data from the study by Gane et al. suggest that excluding ribavirin compromises the efficacy of sofosbuvir. The use of ribavirin has been associated with hemolytic anemia, a condition that requires close attention, especially in patients with the most pressing need for treatment, such as those with cirrhosis. Even so, the studies by Jacobson et al. and Lawitz et al. suggest an acceptable safety profile for sofosbuvir plus ribavirin, with low rates of anemia and leukopenia among patients receiving this regimen, as compared with standard-of-care therapy. On the other hand, a note of caution is appropriate, since long-term data in larger populations are lacking, and rare but irreversible adverse events still may emerge with wider use of sofosbuvir.

What are we to conclude from these studies? The low incidence of side effects, the relatively short duration of treatment, and the pangenotypic properties of the drugs are strong selling points of a sofosbuvir–ribavirin regimen and will probably lower the threshold for HCV treatment for both patients and physicians. The likely next step is to combine sofosbuvir with other direct-acting antivirals to enhance its potency. Is the interferonologist down and out? I do not think so, but it is surely time for reeducation.

Disclosure forms provided by the author are available with the full text of this article at NEJM.org.

This article was published on April 23, 2013, at NEJM.org.

Source Information

From the Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.

References

Source

Ribavirin Levels 50% Higher With Than Without Telaprevir

14th International Workshop on Clinical Pharmacology of HIV Therapy, April 22-24, 2013, Amsterdam

Mark Mascolini

Ribavirin area under the concentration-time curve (AUC) was 50% higher with telaprevir than without telaprevir in 21 HCV-positive people enrolled in a trial of telaprevir plus pegylated interferon/ribavirin (PR) versus PR alone [1]. That finding, and other study results, could partly explain why anemia is more frequent with than without telaprevir in people taking PR.

Both telaprevir and boceprevir, the other licensed HCV protease inhibitor, contribute to anemia in people taking PR for HCV. Pinning down the mechanism is difficult because telaprevir, boceprevir, and ribavirin all may contribute independently to anemia risk.

This analysis included 21 treatment-naive people infected with HCV genotype 1 and enrolled in an ongoing trial of telaprevir plus PR versus PR alone (NCT01097395). Five people were taking triple therapy and 16 only PR. Ribavirin dose was based on weight, either 1000 or 1200 mg. After 9 to 14 weeks of therapy--with ribavirin levels at steady state--the researchers collected plasma, red blood cells, and peripheral blood mononuclear cell (PBMC) samples before and up to 12 hours after dosing.

Median ages were 56 and 50 in the triple-therapy and dual-therapy groups, while median respective weights were 78 and 77. All triple-therapy patients were men, as were 9 of 15 dual-therapy patients. Three people (60%) in the triple-therapy group and 5 (32%) in the dual-therapy group had fibrosis stage 3-4.

Ribavirin AUC was 1.54 times higher in the triple-therapy group than in people not taking telaprevir (P = 0.002). In red blood cells, ribavirin monophosphate, diphosphate, and triphosphate were 3.3-fold (P = 0.03), 2.3-fold (P = 0.0005), and 2.4-fold (P = 0.001) higher with than without telaprevir. In PBMCs, ribavirin mono-, di-, and triphosphate levels were 2.5-fold (P = 0.003), 3-fold (P = 0.006), and 2-fold (P = 0.04) higher with than without telaprevir.

The researchers "speculate that increased ribavirin exposures due to telaprevir might be a factor in the anemia observed during telaprevir-based antiviral therapy of HCV."

Reference

1. Hammond KP, Jimmerson L, MacBrayne CE, et al. Increased plasma and intracellular ribavirin concentrations associated with telaprevir use. 14th International Workshop on Clinical Pharmacology of HIV Therapy, April 22-24, 2013,

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All-Oral Triple Combo Has High HCV Cure Rate

By John Gever, Deputy Managing Editor, MedPage Today

Published: April 24, 2013

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania

AMSTERDAM -- Hitting hepatitis C virus (HCV) from three directions was a winner in a phase II trial involving patients with the particularly hard-to-treat viral genotype 1a, researchers said here.

Sustained 12-week viral response (SVR12) rates, indicating HCV viral loads too low to be measured, were seen in 89% to 94% of patients receiving various regimens that combined the investigational agents daclatasvir, asunaprevir, and BMS-791325, according to data slated for presentation this week at the annual meeting of the European Association for the Study of the Liver.

Two of the 66 patients enrolled in the trial had serious adverse events, but one was judged to be unrelated to study medications and the other occurred after a patient with viral breakthrough went on to receive conventional anti-HCV drugs.

Earlier results were reported last fall by Gregory Everson, MD, of the University of Colorado at Aurora, at which point SVR12 results were available for only one of the ongoing study's four arms. Everson is to present SVR12 outcomes for two of the remaining three arms at the EASL meeting, as well as some SVR24 and SVR36 (24- and 36-week sustained viral responses, respectively) results.

Data were made available at a press conference held prior to Everson's presentation and separately by the study's sponsor, Bristol-Myers Squibb.

Daclatasvir is an NS5A replication complex inhibitor, asunaprevir is an NS3 protease inhibitor, and BMS-791325 is a non-nucleoside NS5B polymerase inhibitor.

The trial assigned previously untreated patients to one of four regimens, all of which involved daclatasvir once daily and the other two agents twice daily. Two doses of BMS-791325 were tested (75 and 150 mg) and treatment duration was either 12 or 24 weeks.

Nearly three-quarters of patients had HCV genotype 1a, with the remainder genotyped as HCV 1b. In an earlier study of daclatasvir and asunaprevir, patients with genotype 1a fared poorly. Leaders of the current trial suspected that adding the polymerase inhibitor could boost responses.

SVR12 results for patients receiving the regimen with 150 mg of BMS-791325 for 24 weeks are still not available. For the other three arms, SVR12 rates were as follows:

  • Low-dose BMS-791325, 12 weeks: 94%
  • Low-dose BMS-791325, 24 weeks: 94%
  • High-dose BMS-791325, 12 weeks: 89%

In addition, SVR24 rates for the low-dose 12- and 24-week treatment groups were 94% and 88%, respectively. In the low-dose group treated for 12 weeks, the SVR36 rate was 88%.

Those data were from an intent-to-treat analysis that classified three patients who failed to complete the planned follow-up as treatment failures. When the analysis was restricted to 28 patients for whom complete post-treatment data were available, all 28 met SVR24 or SVR36 criteria.

Two patients, both receiving the higher dose of BMS-791325, had viral breakthrough. One other patient, also in one of the high-dose groups, experienced a relapse after initially successful treatment.

The most common adverse events, each seen in at least 10% of patients, were headache, asthenia, diarrhea, and nausea. None of these were considered serious except for a case of grade 3 headache, which resolved in one week without interrupting study medications.

Although some elevations in liver enzymes and bilirubin were seen, none reached grade 3 or 4. One case of lymphopenia occurred in a patient with an influenza infection.

No results stratified by patient genotype were available prior to Everson's presentation.

Press conference co-moderator Mark Thursz, MD, of St. Mary's Hospital in London, said the data looked "extremely encouraging, but [based on] small numbers in a phase II study."

He noted that a race is already on to find replacements for the current oral anti-HCV drugs boceprevir (Victrelis) and telaprevir (Incivek), approved less than 2 years ago, because of their substantial side-effect profiles. These agents are now "in sick bay," he said, and before very long are likely to be replaced in clinical practice with newer drugs such as asunaprevir in combination regimens.

The study was funded by Bristol-Myers Squibb.

Everson reported that he had unspecified relationships with commercial entities that could be perceived as having a connection with the presentation.

Thursz reported relationships with Gilead and Abbott.

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Research finds targeted screening for hepatitis C is cost-effective

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April 24, 2013 in Diseases, Conditions, Syndromes

Researchers at the University of Cincinnati have found that targeted screening for populations with a higher estimated prevalence for hepatitis C may be cost-effective.

These findings, published in the April 24, 2013, online edition of the journal Clinical Infectious Diseases, indicate that targeted screening for chronic hepatitis C virus infection is cost-effective when the prevalence of hepatitis C in a population exceeds 0.84 percent (84/10,000).

The study further demonstrates how a screening tool, which can be incorporated into an electronic health record, can target such patients and help in preventing the spread of the illness.

Mark Eckman, MD, Alice Margaret Posey Professor of Internal Medicine, professor in the division of general internal medicine and UC Health physician, and Kenneth Sherman, MD, PhD, Robert & Helen Gould Endowed Chair, professor in the division of digestive diseases and UC Health physician, co-authored the study.

"Hepatitis C is the most common chronic blood-borne infection in the United States and will become an increasing source of morbidity and mortality with aging of the infected population," says Sherman, adding that hepatitis C is a viral disease that leads to inflammation of the liver and can be spread through exchange of bodily fluids with an infected person.

"Our objective in this study was to develop decision analytic models, exploring the cost-effectiveness of screening in populations with varying prevalence of hepatitis C and risks for liver fibrosis—or scarring—in those with the illness who do not receive treatment. Liver fibrosis results in a damaged liver, and the patient eventually needs a transplant, increasing cost of care."

Researchers developed a computerized Markov state transition model—a mathematical framework for modeling decision-making in situations where outcomes are partly due to chance and partly under the control of a decision maker—to examine screening in a U.S. community whose residents showed no symptoms.

"The base case was an ethnically and gender-mixed adult population with no prior knowledge of diagnosis: 49 percent male, 78 percent white, 13 percent black and 9 percent Hispanic, with a mean age of 46 years," says Eckman.

The model explored strategies of screening followed by guideline-based treatment, if needed, and not screening. Effectiveness was measured in quality-adjusted life years (QALYs)—accounting for both duration of survival and quality of life—and costs were measured in U.S. dollars.

"In the base case, screening followed by guideline-based treatment—using boceprevir as the standard antiviral treatment—of those with chronic hepatitis C infection cost roughly $47,000 per QALY—a 'cost-effective' result," says Eckman. "The overall hepatitis C prevalence in the U.S. is reported to be between 1.3 and 1.9 percent, but prevalence varies among patients with different risk factors."

He continues that the marginal cost-effectiveness ratio (mCER) of screening decreases as prevalence increases.

"Below a prevalence of 0.84 percent within a population, the mCER is greater than the generally accepted societal willingness-to-pay threshold of $50,000 per QALY," he says. "Therefore, it is not considered highly cost-effective. However, by targeting screening in populations with a higher estimated prevalence, screening and subsequent treatment of those infected would be cost effective."

"Recently released guidelines by the Centers for Disease Control and Prevention advocate 'birth-cohort' focused screening for those born between 1945 and 1965. However, such a strategy may miss screening higher risk patients born in years outside of this cohort," Eckman adds. "Alternatively, patients with no risk factors for hepatitis C infection, other than their membership in the 'birth cohort,' may be at a low enough risk to make their screening less cost-effective."

Eckman and Sherman "argue for the development and proliferation of tools to assist in the implementation of guidelines. The increasing use of electronic health records and computerized order entry create new opportunities to marry guidelines to practice."

"Perhaps in this manner, targeted and cost-effective screening can become a reality," says Eckman.

Journal reference: Clinical Infectious Diseases

Provided by University of Cincinnati Academic Health Center

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COLUMBIA, S.C., April 24, 2013 /PRNewswire/ -- HarborPath, an organization which provides a single point of access to HIV/AIDS medications through patient assistance programs, welcomes Gilead Sciences as a participating company. Gilead joins Merck and ViiV Healthcare as the third pharmaceutical company to support HarborPath since its launch in July 2012.

"With Gilead's support of this pilot program, we can extend the reach of the organization and offer access to a broader-range of HIV/AIDS medications," said Ken Trogdon, Jr. , President of HarborPath. "We are thankful for the support of our pharmaceutical company partners and we urge others to join our efforts to serve individuals who need access to medications through patient assistance programs. These programs are a safety net for those who cannot afford their medications and they provide access to the life-saving drugs that allow people living with HIV/AIDS to live longer and healthier lives."

HarborPath is currently piloting the program in six states and Washington, D.C., having most recently added a clinic in South Carolina. HarborPath provides a streamlined process for healthcare professionals and case managers to connect individuals living with HIV/AIDS to multiple patient assistance programs using the common application form on the HarborPath website. The donated medications are delivered at no cost to qualified individuals through HarborPath's contracted mail-order pharmacy.

"Access to medicines should never be a barrier to care, and I'm encouraged by HarborPath's efforts to ensure streamlined access to life-saving medications for people living with HIV/AIDS," said Congresswoman Barbara Lee of California, Co-Chair of the Congressional HIV/AIDS Caucus. "All stakeholders, including the government, private sector, faith communities, and the philanthropic community have an important role to play to ensure HIV/AIDS medications reach those who need them."

About HarborPath

HarborPath is a 501(c) (3) organization whose mission is to provide streamlined access to HIV/AIDS medications through patient assistance programs via an online portal. For more information, visit www.harborpath.org.

SOURCE HarborPath

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Public release date: 24-Apr-2013

Contact: Dimple Natali
easlpressoffice@cohnwolfe.com
44-790-013-8904
European Association for the Study of the Liver

Direct-acting antivirals now ready for prime time

Amsterdam, The Netherlands, Wednesday 24 April 2013: New data from a number of clinical trials presented for the first time at the International Liver Congress™ 2013 demonstrate encouraging results in the use of new direct-acting antiviral agents (DAAs) for the treatment of hepatitis C.

The following covers key results from the much anticipated Phase III trials conducted among HCV patients with a range of genotypes (GT 1 to 6) on DAA treatment.

POSITRON

  • A study of interferon (IFN)-ineligible, IFN-intolerant, or IFN-unwilling cirrhotic and non-cirrhotic GT 2 and 3 HCV-infected patients treated with a combination of sofosbuvir and ribavirin for 12 weeks achieved a high SVR12 rate without evidence of resistance. In the POSITRON Phase III trial, the SVR12 rate of 78% for sofosbuvir and ribavirin (161/207) was superior to placebo (0%, p< 0.001) and all 278 patients became HCV RNA negative on treatment. In terms of adverse events only 2% of patients discontinued treatment in the sofosbuvir + ribavirin group due to adverse events vs. 4% in the placebo group.

NEUTRINO

  • Treatment with a combination of sofosbuvir, peginterferon alfa-2a and ribavirin for 12 weeks achieved 90% SVR12 in treatment naïve genotype 1, 4, 5, or 6 HCV-infected patients with no viral resistance detected in failures, according to the results of the Phase III NEUTRINO study. The regimen was well tolerated and is a short, simple and effective treatment option for patients with these genotypes. A total of 327 patients (292 genotype 1, 28 genotype 4, 7 genotype 5/6) were enrolled and received the study drug.

EASL Secretary General Prof. Mark Thursz commented on the studies: "Unlike the US, in Europe and Asia genotype 3 is quite common. As such for European audiences the interferon-free results in genotype 3 are not as impressive as expected; however the side effect profile and lack of viral resistance means that longer treatment durations will be evaluated in the near future. In the meantime, we feel it's not time to bury pegylated interferon just yet."

"Many patients can tolerate 12 weeks of an interferon based regime particularly when it produces SVR rates of more than 90%; so clearly the results of the NEUTRINO study will be welcomed by clinicians and patients" added Prof. Thursz.

STARTVerso™1

  • Faldaprevir, an oral once-daily protease inhibitor, in combination with peginterferon alfa-2a and ribavirin (PegIFN/RBV) significantly increased SVR12 rates in treatment-naïve HCV GT-1 patients in Europe and Japan compared with PegIFN/RBV alone and was well tolerated. In total 652 patients were treated and 88% of patients treated with faldaprevir were eligible to stop all treatment at week 24.

QUEST-1 and -2

  • QUEST-1: Simeprevir, an oral once-daily protease inhibitor, in combination with peginterferon alfa-2a and ribavirin (PegIFN/RBV) achieved SVR12 rates of 80% compared to placebo, 50% (p<0.001). Of the 394 patients, 85% in the simeprevir treatment group were eligible to complete treatments at week 24. On-treatment failure rate was also much lower with simeprevir treatment, compared to placebo.
  • QUEST-2: Simeprevir versus placebo as part of regimen including PegIFN or PegIFN/RBV was well tolerated. SVR12 rates significantly increased in the simeprevir group compared to placebo (81 vs. 50% respectively (p<0.001) and of the 391 patients treated, 91% were eligible to stop all treatment at week 24.

Prof. Mark Thursz commented on the exciting protease inhibitor data showcased at the congress: "With genotype-1 the most common and most challenging type of HCV to cure, both studies have demonstrated extremely encouraging results with cleaner profiles than existing protease inhibitors. It is unlikely telaprevir and boceprevir will remain in the hepatic armoury for much longer."

"We truly are in a prime time for HCV therapy; these effective new treatment options have the potential to pave the way for future interferon-sparing regimens and we look forward to using them in the clinic" added Prof Thursz.

Other promising Phase II data presented at the congress may provide further options:

ELECTRON

  • Results of the ELECTRON study show that all-oral regimens containing sofosbuvir in combination with a second DAA and ribavirin show promising efficacy, with rapid and consistent antiviral suppression in both treatment-naïve patients and prior null responders. High response rates in those treatment arms employing a second agent supports the hypothesis that the addition of another DAA with a different mechanism of action and non-overlapping resistance profile would improve rates of SVR.

IFN and RBV Free Regimen

  • Interim analysis of a Phase II study show that an interferon (IFN)- and ribavirin (RBV)-free regimen of daclatasvir (NS5A inhibitor), asunaprevir (protease inhibitor) and BMS-791325 (non-nucleoside NS5B inhibitor) achieved, overall, an SVR4 of 92% (46/50), SVR12 of 94% (30/32), and SVR24 of 94% (15/16) in treatment-naive genotype (GT) 1 patients, mainly GT1a and IL28B non-CC. Patients were initially randomised (1:1) to daclatasvir 60mg QD, asunaprevir 200mg BID, and BMS-791325 75mg BID for a period of 24 or 12 weeks. Following one month of safety observation, a second cohort was randomized (1:1) to the same regimen but including BMS-791325 150mg BID (24 or 12 weeks). The primary end point was HCV RNA < 25 IU/mL at 12 weeks post-treatment (SVR12). Sixty four of the 66 patients had a HCV RNA < 25 IU/mL by week 4, with no difference in virological responses between 12 and 24 weeks of treatment.

AVIATOR

  • Latest results from the AVIATOR study , using a combination of ABT-450/r (HCV protease inhibitor dosed with ritonavir 100 mg) with ABT-267 (NS5A inhibitor) and/or ABT-333 (non-nucleoside NS5B inhibitor) +/- ribavirin, demonstrate impressive SVR12 in patients with chronic HCV GT1 infection. The overall intention-to-treat SVR12 rate for 12-week treatment with three DAAs in combination with ribavirin was 98.7% (78/79) in treatment-naïve patients, and 93% (42/45) in null responders.

EASL Secretary General Prof. Mark Thursz commented further: "With such high success rates and increased safety and tolerability with novel DAAs, patients can be optimistic about oral treatment regimens in the not-too-distant future."

Disclaimer: The data referenced in this release is based on the submitted abstract. More recent data may be presented at the International Liver Congress™ 2013.

###

Notes to Editors

Worldwide estimates indicate that approximately 200 million people are chronically infected with the hepatitis C virus and at risk of developing liver cirrhosis and/or liver cancer. Every year, 3 million people are infected with hepatitis C and more than 350,000 people die from hepatitis C-related liver diseases.

About EASL

EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

EASL's main focus on education and research is delivered through numerous events and initiatives, including:

  • The International Liver CongressTM which is the main scientific and professional event in hepatology worldwide
  • Meetings including Monothematic and Special conferences, Post Graduate courses and other endorsed meetings that take place throughout the year
  • Clinical and Basic Schools of Hepatology, a series of events covering different aspects in the field of hepatology
  • Journal of Hepatology published monthly
  • Participation in a number of policy initiatives at European level

About The International Liver CongressTM 2013

The International Liver Congress™ 2013, the 48th annual meeting of the European Association for the study of the Liver, is being held at the RAI Convention Centre in Amsterdam from April 24 – 28, 2013. The congress annually attracts in excess of 9000 clinicians and scientists from around the world and provides an opportunity to hear the latest research, perspectives and treatments of liver disease from principal experts in the field.

1 Jacobson, I et al, TREATMENT WITH SOFOSBUVIR+RIBAVIRIN FOR 12 WEEKS ACHIEVES SVR12 OF 78% IN GT2/3 INTERFERON- INELIGIBLE, -INTOLERANT, OR -UNWILLING PATIENTS: RESULTS OF THE PHASE 3 POSITRON TRIAL. Presented at the International Liver Congress™ 2013

2 Lawitz, E et al, SOFOSBUVIR + PEGINTERFERON + RIBAVIRIN FOR 12 WEEKS ACHIEVES 90% SVR12 IN GENOTYPE 1, 4, 5, OR 6 HCV INFECTED PATIENTS: THE NEUTRINO STUDY. Presented at the International Liver Congress™ 2013

3 Ferenci, P et al, FALDAPREVIR PLUS PEGYLATED INTERFERON ALFA-2A AND RIBAVIRIN IN CHRONIC HCV GENOTYPE-1 TREATMENT-NAÏVE PATIENTS: FINAL RESULTS FROM STARTVERSO1, A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE III TRIAL. Presented at the International Liver Congress™ 2013

4 Jacobson, I et al, SIMEPREVIR (TMC435) WITH PEGINTERFERON/RIBAVIRIN FOR CHRONIC HCV GENOTYPE-1 INFECTION IN TREATMENT-NAÏVE PATIENTS; RESULTS FROM QUEST-1, A PHASE III TRIAL. Presented at the International Liver Congress™ 2013

5 Manns M, et al, SIMEPREVIR (TMC435) WITH PEGINTERFERON/RIBAVIRIN FOR CHRONIC HCV GENOTYPE-1 INFECTION IN TREATMENT-NAÏVE PATIENTS; RESULTS FROM QUEST-2, A PHASE III TRIAL. Presented at the International Liver Congress™ 2013

6 Gane EJ, et al, ALL-ORAL SOFOSBUVIR-BASED 12-WEEK REGIMENS FOR THE TREATMENT OF CHRONIC HCV INFECTION: THE ELECTRON STUDY Presented at the International Liver Congress™ 2013

7 Everson, GT et al, INTERIM ANALYSIS OF AN INTERFERON (IFN)- AND RIBAVIRIN (RBV)-FREE REGIMEN OF DACLATASVIR (DCV), ASUNAPREVIR (ASV), AND BMS-791325 IN TREATMENT-NAIVE, HEPATITIS C VIRUS GENOTYPE 1-INFECTED PATIENTS. Presented at the International Liver Congress™ 2013

8 Kowdley, KV et al, SAFETY AND EFFICACY OF INTERFERON-FREE REGIMENS OF ABT-450/R, ABT-267, ABT-333 +/- RIBAVIRIN IN PATIENTS WITH CHRONIC HCV GT1 INFECTION: RESULTS FROM THE AVIATOR STUDY. Presented at the International Liver Congress™ 2013

9 EASL Clinical Practice Guidelines: Management of hepatitis C virus infection. European Association for the Study of the Liver. Journal of Hepatology 2011;55:245

10 Hepatitis C Fact Sheet. World Health Organisation factsheet. Available at http://www.who.int/mediacentre/factsheets/fs164/en/index.html. Last accessed 28.03.13

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24-Apr-13 Stockholm, Sweden — Medivir AB (OMX: MVIR) today announces that Janssen-Cilag International NV (Janssen) today has submitted a Marketing Authorization Application to the European Medicines Agency (EMA) seeking approval for simeprevir (TMC435).

”The filing of simeprevir in Europe represents the third filing in major regions in the last two months. It shows the commitment and speed with which our partner Janssen acts in the process of bringing new hepatitis C treatments to the market”, said Maris Hartmanis, CEO of Medivir AB.

The regulatory submission for simeprevir is supported by data from three phase III studies in patients with genotype 1 hepatitis C: QUEST-1 and QUEST-2 in treatment-naïve patients, and PROMISE in patients who have relapsed after prior interferon-based treatment. The filing for the treatment of patients with the genotype 4 virus is based on phase II data and an ongoing phase III study.

Simeprevir is a new generation NS3/4A protease inhibitor, administered as a capsule once daily with pegylated interferon and ribavirin for the treatment of genotype 1 and 4 chronic hepatitis C in adult patients. Genotype 1 is the most prevalent form of hepatitis C virus (HCV) worldwide.

For more information please contact:

Rein Piir, EVP Corporate Affairs & IR
Mobile: +46 708 537 292

About Simeprevir

Simeprevir is a new generation NS3/4A protease inhibitor jointly developed by Medivir and Janssen for the treatment of chronic hepatitis C in adult patients with compensated liver disease. Janssen recently submitted a new drug application for simeprevir in Japan and the United States.

For additional information about simeprevir clinical trials, please visit www.clinicaltrials.gov.
About Hepatitis C

Hepatitis C, a blood-borne infectious disease of the liver and a leading cause of chronic liver disease and liver transplants, is a rapidly evolving treatment area with a clear need for innovative treatments. Approximately 150 million people are infected with hepatitis C worldwide, and 350,000 people per year die from the disease.

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 in late phase III clinical development for hepatitis C that is being developed in collaboration with Janssen R&D Ireland. 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

Source

Public release date: 23-Apr-2013

Contact: Lauren Woods
law2014@med.cornell.edu
646-317-7401
Weill Cornell Medical College

Drug therapy offers high cure rate for 2 hepatitis C subtypes

A new drug is offering dramatic cure rates for hepatitis C patients with two subtypes of the infection -- genotype 2 and 3, say a team of scientists led by Weill Cornell Medical College researchers. These two subtypes account for approximately 25 percent of hepatitis C infection in the United States.

The drug, called sofosbuvir, offers more effective treatment for most patients studied in a Phase 3 clinical trial who had no other treatment options, report researchers in The New England Journal of Medicine. After three months of combined therapy with sofosbuvir and the antiviral drug ribavirin, the patient response rate for those with genotype 2 was 93 percent, and 61 percent in patients with genotype 3.

This new study is one of several testing new hepatitis C drugs that were published April 23 in an online edition of NEJM. The journal publication coincides with the International Liver Congress 2013 in Amsterdam, the Netherlands, where the results also will be presented.

"The new sofosbuvir therapy offers a much-needed alternative to standard therapy with interferon, which can cause significant side effects for hepatitis C patients," says the study's lead investigator, Dr. Ira Jacobson, chief of the Division of Gastroenterology and Hepatology and Vincent Astor Distinguished Professor of Medicine at Weill Cornell Medical College.

"We have dreamed for years of being able to eliminate interferon from our hepatitis C regimens and this study is one of several that are finally bringing us very close to realizing that goal," says Dr. Jacobson, who is also a gastroenterologist at the Center for Advanced Digestive Care at New York-Presbyterian Hospital/Weill Cornell Medical Center and medical director of the Center for the Study of Hepatitis C, a collaboration between Weill Cornell, NewYork-Presbyterian/Weill Cornell and The Rockefeller University.

The 207 patients enrolled in the clinical trial, known as POSITRON, either did not respond to interferon, could not tolerate it or were unwilling to use it, despite the fact that there were no other treatment options available to them.

"This new treatment represents a paradigm shift in the way that hepatitis C is going to be treated," says Dr. Jacobson. "We are achieving the same or higher cure rates in many patients with sofosbuvir, compared to interferon, and we are doing it in half the time with a drug that has a remarkable safety profile."

Dr. Jacobson estimates that up to half of patients with hepatitis C infection either can't use interferon or don't want to use it. "Sofosbuvir is an extremely promising treatment for this population. It is widely hoped that combinations of potent antiviral drugs will eventually replace the use of interferon, in general, for most hepatitis C patients."

The drug sofosbuvir works by interfering with the ability of the hepatitis C virus to replicate. The drug also confers a high barrier to developing the complication of drug resistance. The U.S. Food and Drug Administration (FDA) has not yet approved sofosbuvir. However, results of the four clinical trials published in the NEJM were used to support the regulatory filing submitted to the FDA by the drug's developer, Gilead Sciences, Inc.

No Treatment Options for Many Patients

Approximately 170 million people are infected with hepatitis C worldwide and 350,000 people die each year from the disease. According to federal statistics, there are an estimated four million people in the U.S. infected with hepatitis C. As there are often no symptoms, most people with hepatitis C are unaware that they are infected.

When left untreated, hepatitis C virus can cause progressive liver disease such as cirrhosis, liver cancer and liver failure. The virus is spread by contact with infected blood, such as through blood transfusions, injection drug use or sexual contact.

There are seven major genotypes of hepatitis C, but most cases are 1, 2 or 3. Genotype 1 is the most common subtype in the U.S. Genotypes 2 and 3 are more common in Europe than in the U.S. and genotype 3 is very prevalent on the Indian subcontinent.

In the study, three-fourths of participants (207) were randomized to treatment with sofosbuvir and ribavirin while one-fourth (71) of participants were randomized to a placebo treatment. All of the patients either did not respond to interferon, or did not want to use it. "This mirrors what happens frequently in the clinic," says Dr. Jacobson. "Between 15 and 30 percent of patients with hepatitis C genotype 2 or 3 infections do not have a response to interferon therapy and do not have alternate treatment options."

Patients were enrolled internationally at 63 sites in the United States, Canada, Australia and New Zealand.

Study results show the response rate for all treated patients with sofosbuvir was 78 percent compared to 0 percent in participants treated with placebo agents. Patients with genotype 2 had a higher cure rate (93 percent) than those with genotype 3 (61 percent), and patients without cirrhosis had a higher response rate (81 percent) compared with participants diagnosed with cirrhosis (61 percent).

The results of another clinical trial, led by Dr. David R. Nelson of the University of Florida at Gainesville, were incorporated into this NEJM manuscript publication. This clinical trial study, called FUSION, was designed to test sofosbuvir and ribavirin in hepatitis C patients with genotype 2 or 3 who had failed interferon therapy.

In FUSION, the drug regimen was tested for both 12 and 16 weeks in patients with genotype 2 or 3. The findings showed that extended use of sofosbuvir resulted in a higher cure rate in both genotypes, but that the difference seen in genotype 3 was highly significant. For genotype 2, 12 versus 16 weeks of treatment resulted in response rates of 86 percent compared to 94 percent; and for genotype 3, the response rates were 30 percent versus 62 percent, respectively.

"Given the absence to date of alternative therapies for patients with genotype 2 or 3 who have failed interferon therapy or for whom it is not an option, treatment with the new sofosbuvir regimen offers a vast improvement," Dr. Jacobson says. "But the optimal duration of treatment for genotype 3 patients, in order to maximize their chance of cure, remains undefined. It could be longer than 16 weeks." Dr. Jacobson adds that future clinical studies will continue to define the optimal length of treatment duration for patients with genotype 3, and that other antiviral drugs in combination with sofosbuvir might shorten the duration of treatment needed to maximize the rates of response.

###

Both the POSITRON and FUSION studies were funded by Gilead Sciences. Another paper in the same edition of the NEJM reports two additional studies of sofosbuvir-containing therapy, one evaluating a 12 week regimen of peginterferon, ribavirin and sofosbuvir in patients with genotypes 1, 4, 5 and 6 who have never been treated before; the other reporting results of a trial comparing 24 weeks of peginterferon and ribavin with 12 weeks of sofosbuvir and ribavirin in treatment naïve patients with genotypes 2 and 3.

Dr. Jacobson is a consultant, lecturer and a funded research investigator for Gilead Sciences.

As medical director of the collaborative Center for the Study of Hepatitis C at Weill Cornell, NewYork-Presbyterian/Weill Cornell and Rockefeller, Dr. Jacobson's research has long been funded by Maurice R. Greenberg, The Starr Foundation and the Greenberg Medical Research Institute. The Center, founded in 2000, is the only comprehensive, multidisciplinary center dedicated to the study of hepatitis C and hepatic disease in the New York tri-state area.

The study co-authors include Dr. Stuart C. Gordon from Henry Ford Health Systems, Detroit, Mich,; Dr. Kris V. Kowdley from Virginia Mason Medical Center, Seattle, Wash.; Dr. Eric M. Yoshida from University of British Columbia, Vancouver, Canada; Dr. Jordan Feld from the University of Toronto, Canada; Dr. Maribel Rodriguez-Torres of Fundacion de Investigacion, San Juan, Puerto Rico; Dr. Mark S. Sulkowski from Johns Hopkins University School of Medicine, Baltimore, Md.; Dr. Mitchell L. Shiffman from the Liver Institute of Virginia, Bon Secours Hampton Roads Health System, Newport News, Va.; Dr. Eric Lawitz from University of Texas Health Science Center, San Antonio, Texas; Dr. M. Tarek Al-Assi from Texas Digestive Disease Consultants, Arlington, Texas; Dr. Gregory Everson from University of Colorado Denver, Aurora, Colo.; Dr. Michael Bennett from Medical Associates Research Group, San Diego, Calif.; Dr. Eugene Schiff from the University of Miami, Miami, Fla.; Dr. Keyur Patel of Duke University, Durham, N.C.; Dr. Stephen Pianko of Monash Medical Centre and Monash University, Melbourne, Australia; and Dr. G. Mani Subramanian, Dr. Di An, Dr. Ming Lin, Dr. John McNally, Dr. Diana Brainard, Dr. William T. Symonds and Dr. John G. McHutchison from Gilead Sciences, in Foster City, Calif.

Weill Cornell Medical College

Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit weill.cornell.edu.

Source

Also See: Data from Phase 3 Studies of Gilead’s Sofosbuvir for Hepatitis C To Be Presented at 48th Annual EASL Meeting; Findings Published Online Today in The New England Journal of Medicine

Idenix

CAMBRIDGE, Mass., April 24, 2013 (GLOBE NEWSWIRE) -- Idenix Pharmaceuticals, Inc. (Nasdaq:IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral diseases, today reported detailed resistance data from in vitro studies and from a three-day monotherapy clinical trial of IDX719, the Company's once-daily, potent, pan-genotypic NS5A inhibitor for the treatment of hepatitis C virus (HCV) infection. These data are being presented on Saturday, April 27, in a poster session at the 48th Annual Meeting of the European Association for the Study of the Liver (EASL), which is being held April 24 - 28, 2013 in Amsterdam, The Netherlands.

Data from the three-day proof-of-concept study demonstrated that IDX719 was well-tolerated at daily doses up to 100 mg and showed potent antiviral activity across HCV genotypes 1-4, with mean maximal viral load reductions up to approximately 4.0 log10 IU/mL. These data were supported by earlier in vitro findings. Clinical plasma samples at baseline, at end of treatment and at one week post-treatment were sequenced for mutations in NS5A at known IDX719 resistance-associated locations.

  • The most common treatment-emergent resistant mutations were detected at NS5A positions 28, 31 and 93. The profile of these mutations varied among genotypes.
  • The only resistance mutation present at baseline found to negatively affect IDX719 response was M31 in GT2-infected patients. In contrast, all GT4-infected patients had virus with M31 at baseline and responded favorably to IDX719 treatment.
  • A GT1b-infected patient with a baseline Y93H mutation, which confers in vitro resistance to IDX719, achieved a 2.79 log10 IU/mL viral load reduction after three days of once-daily 25 mg IDX719, indicating that IDX719 can retain activity against virus with known resistance mutations.

The poster presentation is titled, "Treatment-Emergent Variants Following 3 Days of Monotherapy with IDX719, a Potent, Pan-Genotypic NS5A Inhibitor, in Subjects Infected with HCV Genotypes 1-4" (Abstract No. 1209).

"These additional resistance data support the promising profile of IDX719 as a potent, pan-genotypic component of future HCV combination treatment regimens," commented Douglas Mayers, M.D., Chief Medical Officer of Idenix. "We look forward to evaluating IDX719 as part of all-oral combination therapies through our collaboration with Janssen, beginning with the initiation of a phase II clinical trial of IDX719 and simeprevir in the first half of this year."

ABOUT IDX719

IDX719 is an NS5A inhibitor with low picomolar, pan-genotypic antiviral activity in vitro. To date, IDX719 has been safe and well tolerated after single and multiple doses of up to 100 mg in healthy volunteers (n=36; up to 7 days duration) and HCV-infected patients (n=69; up to 3 days duration). There have been no treatment-emergent serious adverse events reported in the program. IDX719 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 HEPATITIS C

Hepatitis C virus is a common blood-borne pathogen infecting three to four million people worldwide annually. The World Health Organization (WHO) estimates that more than 170 million people worldwide are chronically infected with HCV, representing a nearly 5-fold greater prevalence than human immunodeficiency virus.

ABOUT IDENIX

Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical Company engaged in the discovery and development of drugs for the treatment of human viral diseases. Idenix's current focus is on the treatment of patients with HCV. For further information about Idenix, please refer to www.idenix.com.

FORWARD-LOOKING STATEMENTS

This press release contains "forward-looking statements" for purposes of the safe harbor provisions of The Private Securities Litigation Reform Act of 1995. For this purpose, any statements contained herein that are not statements of historical fact may be deemed forward-looking statements. Without limiting the foregoing, the words "expect," "plans," "anticipates," "intends," "will," and similar expressions are also intended to identify forward-looking statements, as are any expressed or implied statements with respect to: the Company's plans to continue to developing nucleotide polymerase inhibitors for HCV; its clinical development plans for its uridine nucleotide analog drug candidate and IDX719; its plans to advance other preclinical nucleotides; and statements regarding the efficacy and safety of its clinical compounds. Actual results may differ materially from those indicated by such forward-looking statements as a result of risks and uncertainties, including but not limited to the following: there can be no guarantees that the Company will advance any clinical product candidate or other component of its potential pipeline to the clinic, to the regulatory process or to commercialization due to numerous risks inherent in pharmaceutical research and development; management's expectations could be affected by unexpected regulatory actions or delays; uncertainties relating to, or unsuccessful results of, preclinical and clinical trials, including additional data relating to the ongoing clinical trials evaluating its product candidates; the Company's ability to obtain additional funding required to conduct its research, development and commercialization activities; competition; and the Company's ability to obtain, maintain and enforce patent and other intellectual property protection for its product candidates and its discoveries. Such forward-looking statements involve known and unknown risks, uncertainties and other important factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. These and other risks which may impact management's expectations are described in greater detail under the heading "Risk Factors" in the Company's annual report on Form 10-K for the year ended December 31, 2012, as filed with the Securities and Exchange Commission (SEC) and in any subsequent periodic or current report that the Company files with the SEC.

All forward-looking statements reflect the Company's estimates only as of the date of this release (unless another date is indicated) and should not be relied upon as reflecting the Company's views, expectations or beliefs at any date subsequent to the date of this release. While Idenix may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, even if the Company's estimates change.

CONTACT: Idenix Pharmaceuticals Contact:

Teri Dahlman (617) 218-7987

Source

Vertex

April 24, 2013

- Interim analysis of the Phase 3b CONCISE study showed SVR12 rates of 87 percent with 12 total weeks of treatment and 97 percent with 24 total weeks of treatment among people who achieved RVR and completed 12 weeks of treatment -

AMSTERDAM--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced new data from an interim analysis of the exploratory global Phase 3b CONCISE study evaluating the potential to shorten total treatment with telaprevir combination therapy to 12 weeks in certain people with genotype 1 chronic hepatitis C virus (HCV) infection who have the IL28B CC genotype. In the CONCISE trial, telaprevir was administered twice daily in combination with pegylated-interferon and ribavirin. Of the 239 people in the study, 159 people completed 12 weeks of telaprevir combination treatment and had undetectable hepatitis C virus at week four of treatment (rapid viral response, or RVR) and were eligible to be randomized. One hundred seven1 people were randomized to receive no further treatment and 52 people were randomized to receive an additional 12 weeks of treatment with pegylated-interferon and ribavirin alone, for a total of 24 weeks of treatment. In the 12-week total treatment group, of the 85 people with data available at the time of the interim analysis, 87 percent (74/85) had undetectable hepatitis C virus 12 weeks after the end of treatment (SVR12). In the 24-week treatment group, of the 30 people with data available at the time of the interim analysis, 97 percent (29/30) achieved SVR12.

This study includes people with genotype 1 chronic HCV who were new to treatment or who had relapsed after at least one prior course of treatment with pegylated-interferon and ribavirin alone. Approximately one-third of people with hepatitis C have the ‘CC' genotype, which has been associated with higher sustained viral response (SVR, or viral cure) rates and faster response to interferon-based treatment. The safety profile of telaprevir combination therapy observed in the CONCISE study through the time of the interim analysis was similar to that seen in previously reported clinical trials. The interim results of this study will be presented at the 48th Annual Meeting of the European Association for the Study of the Liver (EASL) in Amsterdam, Netherlands, April 24 to 28, 2013 (poster #881).

Telaprevir is approved for use in combination with pegylated-interferon and ribavirin by the U.S. Food and Drug Administration (FDA) and Health Canada under the brand name INCIVEK® (telaprevir) tablets for people with genotype 1 chronic HCV infection with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). INCIVEK's approved dosing schedule is two 375mg tablets three times daily, and it is given for 12 weeks in combination with pegylated-interferon and ribavirin. After the first 12 weeks, all patients stop receiving INCIVEK and continue treatment with pegylated-interferon and ribavirin alone for an additional 12 weeks or 36 weeks.

About CONCISE

CONCISE is a randomized, placebo-controlled, global, multi-center Phase 3b study designed to evaluate the safety and efficacy of a 12-week regimen of telaprevir tablets in combination with pegylated-interferon and ribavirin in people with genotype 1 chronic HCV infection who have the IL28B CC genotype. In this study, telaprevir was dosed as three 375mg tablets twice daily. The study includes 239 people with hepatitis C who are new to treatment as well as those who relapsed after at least one prior course of treatment with pegylated-interferon and ribavirin alone. The primary endpoint of the study is the proportion of randomized people who achieve a sustained viral response (HCV RNA < lower limit of quantification) 12 weeks after the last planned dose of study drug (SVR12). All study participants were assigned to receive telaprevir in combination with pegylated-interferon and ribavirin for 12 weeks. People who continued all study drugs for 12 weeks and achieved a rapid viral response to treatment (measured as undetectable HCV RNA at week 4) were randomized 2:1 to receive no further treatment or an additional 12 weeks of pegylated-interferon and ribavirin alone. People who did not achieve a rapid viral response or who did not continue all study drugs for 12 weeks were assigned a total pegylated-interferon and ribavirin treatment duration of 24 or 48 weeks based on virologic response.

About INCIVEK

INCIVEK® (telaprevir) tablets is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. INCIVEK has been prescribed to more than 60,000 patients in the United States. Approximately three out of four U.S. patients who are prescribed a direct-acting antiviral for the treatment of genotype 1 chronic hepatitis C (HCV) are prescribed INCIVEK combination therapy.

In Phase 3 clinical studies, 79 percent of people who had not previously been treated for HCV achieved a viral cure following treatment with INCIVEK combination therapy, compared with 46 percent of those who received pegylated-interferon and ribavirin (P/R) alone. Among people who were treated previously but did not achieve a viral cure, in the Phase 3 studies: 86 percent of relapsers achieved a viral cure with INCIVEK combination therapy compared to 22 percent with P/R alone; 59 percent of partial responders achieved a viral cure compared with 15 percent with P/R alone; and 32 percent of null responders achieved a viral cure compared with 5 percent with P/R alone. In addition, many people are eligible to complete treatment with INCIVEK combination therapy in 24 weeks — half the time required for treatment with P/R alone.

INCIVEK was approved by the U.S. Food and Drug Administration (FDA) in May 2011 and by Health Canada in August 2011 for use in combination with pegylated-interferon and ribavirin for adults with genotype 1 chronic hepatitis C with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). INCIVEK is approved for people who are new to treatment, and for people who were treated previously with interferon-based treatment but who did not achieve a sustained viral response, or viral cure (relapsers, partial responders and null responders).

Vertex developed telaprevir in collaboration with Janssen and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK (in-SEE-veck). Janssen has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. In September 2011, telaprevir was approved in the European Union and Switzerland. Telaprevir is known as INCIVO® in Europe. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries. In September 2011, telaprevir was approved in Japan and is known as Telavic®.

IMPORTANT SAFETY INFORMATION

Indication

INCIVEK® (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.

Important Safety Information

INCIVEK® (telaprevir) should always be used in combination with peginterferon alfa and ribavirin. INCIVEK combination treatment may cause serious side effects including skin rash and serious skin reactions, anemia (low red blood cell count) that can be severe, and birth defects or death of an unborn baby.

Skin rashes are common with INCIVEK combination treatment. Sometimes these skin rashes and other skin reactions can become serious, require treatment in a hospital, and may lead to death. Patients should call their healthcare provider right away if they develop any skin changes during treatment with INCIVEK. Their healthcare provider will decide if they need treatment or if they need to stop INCIVEK or any of their other medicines. Patients should not stop taking INCIVEK combination treatment without talking with their healthcare provider first.

Patients' healthcare providers will do blood tests regularly to check for anemia. If anemia is severe, the healthcare providers may tell them to stop taking INCIVEK.

INCIVEK combined with peginterferon alfa and ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant. Females who can become pregnant and females whose male partner takes these medicines must have a negative pregnancy test before starting treatment, every month during treatment, and for 6 months after treatment ends. Patients must use two forms of effective birth control during treatment and for 6 months after all treatment has ended. These two forms of birth control should not contain hormones, as these may not work during treatment with INCIVEK.

INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life-threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.

The most common side effects of INCIVEK combination treatment include itching, nausea, diarrhea, vomiting, anal or rectal problems (including hemorrhoids, discomfort , burning or itching around or near the anus), taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare provider about any side effect that bothers them or doesn't go away.

Please see full Prescribing Information including Boxed Warning, and the Medication Guide for INCIVEK available at www.INCIVEK.com.

About Hepatitis C

Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.2 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.2 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.2 Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.3 If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.4,5

More than 170 million people worldwide are chronically infected with hepatitis C.6 In the United States, up to 5 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.7,8 Hepatitis C is four times more prevalent in the United States compared to HIV.8 The majority of people with hepatitis C in the United States were born between 1945 and 1965, accounting for 82 percent of people with the disease.9 Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 15,000 deaths annually.10,11 By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.12

About Vertex

Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.

Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, Mass., we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. Today, Vertex has more than 2,000 employees around the world, and for three years in a row, Science magazine has named Vertex one of its Top Employers in the life sciences.

Vertex's press releases are available at www.vrtx.com.

(VRTX-GEN)

Footnote:

1 One person had genotype 6 HCV infection and was excluded from the efficacy analysis but included in the safety analysis.

References:

2 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf Updated June 2010. Accessed March 29, 2013.

3 Pearlman BL and Traub N. Sustained Virologic Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So Much More. Clin Infect Dis. 2011 Apr;52(7):889-900.

4 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).

5 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.

6 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.

7 Chak, E, et. al. Hepatitis C Virus Infection In USA: An Estimate of True Prevalence. Liver Intl. 2011;1096 -1098.

8 Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. Available at: http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx Updated January 11, 2010. Accessed March 29, 2013.

9 Smith, BD, et al. Hepatitis C Virus Antibody Prevalence, Correlates and Predictors among Persons Born from 1945 through 1965, United States, 1999-2008. AASLD 2011 Annual Meeting.

10 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.

11 Ly KN, et al. The Increasing Burden of Mortality From Viral Hepatitis in the United States Between 1999 and 2007. Ann Intern Med. 2012;156:271-278.

12 Pyenson B, Fitch K, and Iwasaki K. Consequences of Hepatitis C Virus (HCV): Costs of a Baby Boomer Epidemic of Liver Disease. Milliman, Inc. May 2009. Available at: http://www.vrtx.com/assets/pdfs/MillimanReport.pdf Accessed March 29, 2013.

Vertex Pharmaceuticals Incorporated
Media:
Erin Emlock, 617-341-6992
or
Nikki Levy, 617-341-6992
mediainfo@vrtx.com
or
Investors:
Michael Partridge, 617-341-6108
or
Kelly Lewis, 617-961-7530

Source: Vertex Pharmaceuticals Incorporated

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Source

Article | 24 April 2013

Among a number of drug and biotech majors planning to present at the 2013 annual meeting of the European Association for the Study of the Liver (EASL), in Amsterdam (April 24 to 28), the USA’s Bristol-Myers Squibb (NYSE: BMY) will report additional interim Phase II data demonstrating that 12- and 24-week Triple DAA treatment regimens of daclatasvir + asunaprevir + BMS-791325 achieved high rates of sustained virologic response of up to 94%, in treatment-naive, genotype 1 hepatitis C virus (HCV) patients, at time points ranging from four to 36 weeks post-treatment. These data support the continued development of the interferon alfa-, RBV- and RTV-free triple DDA regimen, with Phase III study initiation anticipated to begin by late 2013, the company says.

Health care giant Johnson & Johnson (NYSE: JNJ) will announce primary efficacy and safety results from two Phase III studies - QUEST-1 (n=394) and QUEST-2 (n=391) demonstrating that simeprevir (TMC435) achieved sustained virologic response 12 weeks after the end of treatment (SVR12) in 80 and 81%, respectively, in treatment-naïve genotype 1 chronic hepatitis C adult patients with compensated liver disease, including all stages of liver fibrosis. In both studies, 50% of patients receiving pegylated interferon and ribavirin alone achieved SVR12. Detailed results will be presented at The International Liver Congress 2013 of the European

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Biotech firm Gilead Sciences (Nasdaq: GILD) will report detailed results from four Phase III studies - NEUTRINO, FISSION, POSITRON and FUSION evaluating sofosbuvir for chronic hepatitis C virus infection. In all the four trials, sofosbuvir was administered to about 1,000 patients. Overall SVR12 rates were observed at 50% to 90% in the studies. Analysts at Credit Suisse have a worldwide net present value for sofosbuvir of $10.65 per share (26% of total) for Gilead.

Also, AbbVie (NYSE: ABBV) will report new data from the Phase IIb Aviator trial showing that its investigational direct-acting antivirals (ABT-450/r, ABT-267, ABT-333) continue to demonstrate high sustained viral response rate against genotype 1 HCV infection, across patient types. Results also indicated that >90% SVR was achieved in patients new to treatment and in patients who had previously failed treatment with pegylated interferon and ribavirin. In addition, similar high SVR rates observed after 12 and 24 weeks of treatment in the study. The triple-DAA combination is currently being studied in Phase III studies.

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