Gilead HCV Program, GS-7977

Provided by NATAP

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from Jules od NATAP: Gilead submitted to the FDA approval for the Gilead nucleotide GS-7977+Peg/Rbv 12 weeks for Gt1, and for GS7977+Rbv for Gt2/3 and I think 4/6. They have been studying HIV/HCV coinfection in Gt2 and I think Gt1. The FDA hearing for TMC435 & for GS-7977 appears to be Oct 24/25 2013. There is a lot of research & studies that have been conducted so there is a lot below, you can look at the phase 3 results presented at EASL 2013, link below. Gilead has a protease inhibitor & a non-nuc as well in clinical development, studies presented at EASL 2013. GS-7977 has been studied in combination with BMS' NS5A inhibitor in naives & telaprevir/boceprevir failures with 95-100% SVR rates. In 2014 by June Gilead is expected to submit phase 3 study results to the FDA for their fixed dose combination go GS-7977 + their 1st generation NS5A with and w/o RBV, 12 weeks therapy. At the same time Abbvie will be submitting their Phase 3 study results for their INF-free oral regimen which includes their protease inhibitor, NS5A inhibitor & their non-nuc with & w/o RBV, 12 weeks therapy; GS-7977 mono therapy data is reported in study links below.

GS-7977 & HIV ARTs PK - No Clinically Significant Pharmacokinetic Interactions Between Sofosbuvir (GS-7977) and HIV Antiretrovirals Atripla, Rilpivirine, Darunavir/Ritonavir, or Raltegravir in Healthy Volunteers
http://www.natap.org/2012/AASLD/AASLD_64.htm

GILEAD SUBMITS NEW DRUG APPLICATION TO U.S. FDA FOR SOFOSBUVIR FOR THE TREATMENT OF HEPATITIS C http://www.natap.org/2013/HCV/040813_01.htm

Antiviral Drugs Advisory Committee .........October 24-25 http://www.fda.gov/AdvisoryCommittees/Calendar/ucm153468.htm

Gilead Reports Interim Data From Phase 2 LONESTAR Study - (05/03/13)

EASL 2013
Gilead reported 7 studies results including 4 phase 3 studies and others including their HCV protease inhibitor, 1st & 2nd generation NS5A inhibitors and their non-nuc, ALL with links to each presentation within this report http://www.natap.org/2013/HCV/050313_02.htm

Clin Pharm Workshop at EASL Amsterdam 2013 - Clinical Pharmacology of DAA's for HCV:
What's New and What's in the Pipeline
Gilead Sciences A. Mathias Pres. 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 - Press Release http://www.natap.org/2013/EASL/EASL_02.htm

Sofosbuvir for Previously Untreated Chronic Hepatitis C Infection: 2 phase 3 studies - FISSION (gt2/3), NEUTRINO (gt1) http://www.natap.org/2013/EASL/EASL_32.htm

Gilead's HCV Pipeline Unveiled at EASL http://www.natap.org/2011/EASL/EASL_97.htm

EASL: Sustained Virologic Response With Daclatasvir Plus Sofosbuvir ± Ribavirin (RBV) in Chronic HCV Genotype (GT) 1-Infected Patients Who Previously Failed Telaprevir (TVR) or Boceprevir (BOC) - (04/27/13) EASL/2012: Potent Viral Suppression With the All-Oral Combination of Daclatasvir (NS5A Inhibitor) and GS-7977 (Nucleotide NS5B Inhibitor), +/- Ribavirin, in Treatment-Naive Patients With Chronic HCV GT1, 2, or 3 (100% SVR gt1, 91% gt2) - (04/19/12)

COSMOS Study: SVR4 results of a once daily regimen of simeprevir (TMC435) plus sofosbuvir (GS-7977) with or without ribavirin in HCV genotype 1 null responders http://www.natap.org/2013/CROI/croi_34.htm

AASLD/2012: High Rate of Sustained Virologic Response With the All-Oral Combination of Daclatasvir (NS5A Inhibitor) Plus Sofosbuvir (Nucleotide NS5B Inhibitor), With or Without Ribavirin, in Treatment-Naive Patients Chronically Infected With HCV GT 1, 2, or 3 - (11/13/12)

EASL: No S282T Mutation Detected by Deep Sequencing in a Large Number of HCV Patients Who Received Sofosbuvir With RBV and/or GS-0938: the Quantum Study - (04/29/13)

EASL: GS-5816, a Second-Generation HCV NS5A Inhibitor With Potent Antiviral Activity, Broad Genotypic Coverage, and a High Resistance Barrier - (04/29/13)

EASL: Healthy Volunteer First-in-Human Evaluation of GS-5816, a Novel Second Generation Broad-Genotypic NS5A Inhibitor With Potential for Once-Daily Dosing - (04/29/13)

GILEAD PROVIDES UPDATE ON HEPATITIS C DEVELOPMENT PROGRAMS - update on GS-7977+GS-5885+Rbv in null responders in Electron http://www.natap.org/2013/HCV/010713_02.htm

GS-7977 400 mg QD Safety and Tolerability in the Over 500 Patients Treated for at Least 12 Weeks http://www.natap.org/2012/EASL/EASL_55.htm

Once Daily Sofosbuvir (GS-7977) Regimens in HCV Genotype 1-3: The ELECTRON Trial http://www.natap.org/2012/AASLD/AASLD_31.htm

AASLD: Once Daily Sofosbuvir (GS-7977) plus PEG/RBV In Treatment-Na•ve Patients With HCV Genotype 1, 4, and 6 Infection: The ATOMIC Study http://www.natap.org/2012/AASLD/AASLD_21.htm
http://www.natap.org/2013/HCV/033113_02.htm

Nucleotide Polymerase Inhibitor Sofosbuvir (GS-7977) plus Ribavirin for Hepatitis C - new published study http://www.natap.org/2013/HCV/010413_04.htm

ONCE DAILY DUAL-NUCLEOTIDE COMBINATION OF PSI-938 AND PSI-7977 PROVIDES 94% HCV RNA < LOD AT DAY 14: FIRST PURINE/PYRIMIDINE CLINICAL COMBINATION DATA (THE NUCLEAR STUDY) http://www.natap.org/2011/EASL/EASL_07.htm

Pharmasset Announces Results of a 28-day Phase 2a Study with PSI-7977 for the Treatment of Chronic Hepatitis C Infection http://www.natap.org/2010/HCV/102810_04.htm

AASLD: PSI-7977: ELECTRON Interferon is not required for Sustained Virologic Response in Treatment-Na•ve Patients with HCV GT2 or GT3 - (11/07/11) Lack of Effect of the Nucleotide Analog Polymerase Inhibitor PSI-7977 on Methadone PK and PD http://www.natap.org/2011/AASLD/AASLD_104.htm

PSI-7977 Has No Effect on QTcF Intervals at Therapeutic or Supratherapeutic Doses http://www.natap.org/2011/AASLD/AASLD_103.htm

PSI-7977 with PEG/RBV Elicits Rapid Declines in HCV RNA in Patients with HCV GT-4 and GT-6 http://www.natap.org/2011/hepDART/hepDART_01.htm

High Rapid Virologic Response (RVR) with PSI-7977 Daily Dosing plus PEG-IFN/RBV in a 28-day Phase 2a Trial http://www.natap.org/2010/AASLD/AASLD_49.htm

Gilead Acquires Pharmasset $11 Billion http://www.natap.org/2011/HCV/112111_02.htm

TMC435+GS7977 (Rbv) New Study in Advanced Hepatic Fibrosis- Null Responders & Naives http://www.natap.org/2013/HCV/012213_03.htm

Combination of two complementary nucleotide analogues, PSI-7977 and PSI-938, effectively clears wild type and NS5b: S282T HCV replicons - Comparison with combinations of other antiviral compounds http://www.natap.org/2010/EASL/EASL_28.htm

 

Clinical Trials: GS-7977 Liver Transplant Studies

Clinical Trials

An Open-Label Study to Explore the Clinical Efficacy of GS 7977 With Ribavirin Administered Pre-Transplant in Preventing Hepatitis C Virus (HCV) Recurrence Post-Transplant

The primary objective is to determine if the administration of a combination of GS 7977 and ribavirin to HCV-infected subjects with hepatocellular carcinoma (HCC) meeting the MILAN criteria prior to undergoing liver transplantation for up to 24 weeks can prevent post-transplant re-infection as determined by a sustained post-transplant virological response (HCV RNA < LLoQ) at 12 weeks post-transplant.

Study to Investigate GS-7977 and Ribavirin for 24 Weeks in Subjects With Recurrent Chronic HCV Post Liver Transplant

This is an open-label, single-arm study of GS-7977 and ribavirin (RBV) in subjects who have had a liver transplant which has become re-infected with hepatitis C. The treatment period is 24 weeks with up to 48 weeks of follow up. The total time in this study will last up to 72 weeks not including the screening visit

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On HCV, These Questions Three

Paul Sax • August 25th, 2012

Categories: Infectious Diseases, Patient Care, Research

In the fastest-moving area of ID drug development, answers are eagerly sought to the following questions three:

1. What does the bad news on BMS-986094 — formerly INX-189 — mean for other investigational HCV nucleotides? Severe cardiotoxicity, fatal in one case, has ended the drug’s development. Importantly, nothing similar has thus far been observed with the structurally-similar IDX184, but that drug has been placed on “clinical hold” by the FDA. By contrast, the nucleotide GS-7977 is apparently different enough chemically that studies are for now continuing. One take-home message: drug development is risky business.
2. When will the alphabet soup of terms used to describe HCV treatment response be abandoned? HCV treatment either works, and you’re cured, or it doesn’t. But because the treatment is so cumbersome and so long, there’s a whole slew of ways to describe how things are going before you get to that point. Let’s see, there’s RVR (rapid virologic response, or no virus detected at 4 weeks); eRVR (extended rapid virologic response, or no virus detected at weeks 4 and 12 — used in this study of daclatasvir); EVR (early virologic response, which really isn’t that early, because it’s week 12, and it can be either pEVR — for “partial” — which means HCV RNA drops by more than 2 log but is still detected, or cEVR — for “complete”, which means it’s undetectable); ETR (end of treatment response, or no virus detectable at end of treatment); and of course SVR (sustained virologic response, now available in many flavors, depending on the week after stopping treatment you want to measure it — 2, 4, 8, 12, 16, 24,etc). For now, with IF/RBV +/- telaprevir/boceprevir and “response-guided” therapy still ruling the day, we’re stuck with this mish-mosh of terms, but I suspect most of this stuff will be irrelevant pretty soon, except for the bottom line — how many are cured? Doesn’t that sound better than “How many are SVR-12′d?”
3. So when precisely will these new drugs become available? Seems pretty obvious right now that if you’ve got HCV and can wait for better treatments, you should. Treatment became more effective with telaprevir and boceprevir, but it also got more complicated, toxic, and expensive. Things have to get better, and they will — especially with interferon-free options. Regardless, no one knows exactly when these new drugs will be available for use outside of clinical trials — 2013-2014 a broad estimate — and all kinds of things could hold up their approval (see #1 above). Plus, some patients can’t and shouldn’t wait for better options because they have advanced liver disease. Just this last week, two such individuals came in for evaluation — both with HIV, both with prior treatment failure on IF/RBV, both with Stage 3/4 fibrosis on liver biopsy. Should they wait for daclatasvir, GS-7977, TMC-435, ABT-450/r + ABT-333, etc? Probably not.

For the record … what is the airspeed velocity of an unladen swallow?

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Twelve Weeks of GS-7977 Eliminates HCV as Well as 24 Weeks

From Medscape Medical News

Daniel M. Keller, PhD

May 2, 2012 (Barcelona, Spain) — Twelve weeks of GS-7977 (Gilead Sciences) plus pegylated interferon (pegIFN) and ribavirin was as effective as 24 weeks of treatment in eliminating hepatitis C virus (HCV) genotype 1.

In the phase 2 ATOMIC trial, the drug was found to be safe and well tolerated, according to Kris Kowdley, MD, director of the Liver Center of Excellence, Digestive Disease Institute, Virginia Mason Medical Center, and clinical professor of medicine at the University of Washington in Seattle, who reported the interim results here at the International Liver Congress 2012.

GS-7977 is a potent oral nucleotide analogue inhibitor of HCV NS5B RNA polymerase that has a high barrier to the development of viral resistance. In another trial (PROTON), 12 weeks of GS-7977 in combination with pegIFN/ribavirin followed by 12 weeks of pegIFN/ribavirin was associated with a sustained virologic response (SVR) rate of 91% at 12 (SVR12) and 24 weeks (SVR24) after the end of therapy in patients infected with HCV genotype 1. In light of those results, the aim of the ATOMIC trial was to see if only 12 weeks of therapy could achieve similar results.

In the ATOMIC trial, treatment-naive patients chronically infected with HCV genotype 1 were randomly assigned to 1 of 3 treatment groups: GS-7977 plus pegIFN/ribavirin for 12 weeks (n = 52), GS-7977 plus pegIFN/ribavirin for 24 weeks (n = 125), or GS-7977 plus pegIFN/ribavirin for 12 weeks followed by 12 weeks of GS-7977 alone (n = 75) or in combination with pegIFN/ribavirin (n = 75).

Participants were predominantly white, male, about 50 years of age, had HCV RNA levels of at least 50,000 IU/mL, and had adequate hematologic values. The treatment groups were generally well matched for baseline characteristics.

Drug Combination Yields Rapid and Sustained Virologic Response

In all treatment groups, there was rapid viral suppression over the first 2 weeks of therapy, regardless of interleukin-28B genotype. At the end of treatment, 98% to 99% of patients in each group had achieved HCV RNA levels below the limits of detection, and 92% to 94% achieved a sustained virologic response at 4 weeks (SVR4).

An SVR12 of 90% was achieved in all treatment groups. At the time of the presentation, SVR12 data were available for only some of the patients treated with GS-7977 plus pegIFN/ribavirin for 12 weeks, When only those patients were included, an SVR12 of 94% was achieved, "suggesting that this is a very effective and successful combination," Dr. Kowdley said.

"In fact, when we examined the reasons for failure to achieve an SVR, in most cases it was because of a lack of follow-up rather than because of virologic failure or relapse," he reported. Only 4 patients in the 3 groups experienced a relapse at the SVR4 time point. In the 4 patients who relapsed, no S282T resistance mutations have been detected in the viral NS5B RNA polymerase.

GS-7977 plus pegIFN/ribavirin was generally well tolerated. Less than 5% of patients discontinued the study because of adverse effects related to GS-7977. Most adverse effects were constitutional symptoms generally associated with pegIFN/ribavirin. Neutrophil and lymphocyte counts and hemoglobin and alanine aminotransferase levels quickly improved after pegIFN/ribavirin was discontinued.

Dr. Kowdley concluded that 12 weeks of GS-7977 in combination with pegIFN/ribavirin appears to be as effective as 24 weeks of the same therapy.

Session moderator Mark Thursz, MBBS, MD, professor of hepatology in the Department of Medicine at Imperial College, London, United Kingdom, and secretary general of the European Association for the Study of the Liver, who was not involved in the ATOMIC trial, said during a news conference that SVR24, an absence of viremia for 6 months after the end of treatment, has been the standard definition of cure until recently. Now, "we've started to become used to SVR12 as an end point. I understand that the FDA [US Food and Drug Administration] is now interested in SVR12 if it can be subsequently established as meaning a cure," he said.

"Now the companies are coming to us with SVR4 data.... SVR4 certainly predicts the final outcome. It may not be quite the same as the cure rate, the SVR24 rate, but it's pretty close and gives us a very good indication," Dr. Thursz explained. The implication is that when abstracts are submitted to meetings, "SVR4 is something that we have to take seriously...whereas previously we would regard [the results] as merely interim data," he said.

He told Medscape Medical News that the program for the development of GS-7977 is "progressing very rapidly. I know that Gilead [the drug's manufacturer] is looking at what the best option is" to get the drug approved and available to patients as quickly as possible. He said that some reports suggest that Gilead could file for approval with the FDA in late 2013, with the potential for approval in 2014.

Dr. Kowdley reports being a consultant/advisor for Novartis, Vertex, Pharmasset, Merck, and Abbott; and receiving grants and research support from BMS, Intercept, Abbott, Pharmasset, Merck, Gilead, GSK, Mochida, Conatus, Boeringer Ingelheim, and Genentech. Dr. Thurzs has disclosed no relevant financial relationships.

The International Liver Congress 2012: Abstract 1. Presented April 19, 2012.

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EASL 2012: New HCV Drug Induces Rapid, Durable Drops in Viral Load

From Medscape Medical News

Daniel M. Keller, PhD

April 30, 2012 (Barcelona, Spain) — In 3 phase 2 trials of GS-7977, there was a concordance between the sustained virologic response (SVR) 4 weeks after the end of therapy (SVR4) and SVRs at 12 and 24 weeks after therapy (SVR12 and SVR24) in treatment-naive patients infected with hepatitis C virus (HCV) genotypes 1, 2, or 3.

No patient relapsed after posttreatment week 12, and 99% of patients with SVR4 for whom posttreatment week 12 data were available achieved SVR12, Eric Lawitz, MD, from Alamo Medical Research in San Antonio, Texas, reported here at the International Liver Congress 2012.

GS-7977 (formerly PSI-7977) is a specific nucleotide analogue inhibitor of HCV NS5B RNA polymerase and is taken orally once daily. Previous reports have shown that it has broad antiviral activity against HCV genotypes 1, 2, and 3, with or without interferon, in treatment-naive patients, and has a high barrier to the development of viral resistance.

The aim of the study was to evaluate concordance between SVR4 and SVR12 or SVR24 among treatment-naive patients taking GS-7977 400 mg daily in the PROTON (n = 144), ELECTRON (n = 120), and ATOMIC (n = 332) phase 2 clinical trials. The trial protocols differed somewhat, but in general were various combinations and durations of GS-7977, pegylated interferon (Peg-IFN), and ribavirin.

In the PROTON and ATOMIC trials, depending on viral genotype, patients received GS-7977 plus Peg-IFN/ribavirin for 12 weeks followed by Peg-IFN for 12 weeks, Peg-IFN/ribavirin alone for 48 weeks, GS-7977 plus Peg-IFN/ribavirin for 12 or 24 weeks, GS-7977 plus PegIFN/ribavirin for 12 weeks followed by 12 weeks of GS-7977 alone or by GS-7977 plus ribavirin.

In the ELECTRON trial, some patients with genotypes 2 or 3 virus received similar combinations but only out to 12 weeks. Other patients with genotypes 1, 2, or 3 received GS-7977 plus ribavirin for 12 weeks.

The analysis involved only patients treated with GS-7977 400 mg in combination with interferon, ribavirin, or both for at least 4 weeks who had SVR4 plus SVR12 or SVR4 plus SVR24 data available. Of the 596 patients in the 3 studies, 259 (43%) were eligible for analysis.

At baseline in all treatment groups, mean age ranged from 43 to 52 years, and most patients were white, male, had similar body mass indices (mean, 26 to 28 kg/m²), and had interleukin-28B genotype non-CC. Mean baseline HCV RNA levels were mainly in the range of 6.3 to 6.7 log₁₀ IU/mL.

Dr. Lawitz presented results for virologic response at the end of therapy and for SVR4, SVR12, and SVR24.

"If we look at all regimens and look at the concordance between SVR4 and SVR12, we can see that 249 of the 251 [patients] were concordant between SVR4 and SVR12 — a concordance rate of 99%," he said. "If we look at concordance between SVR4 and SVR24, we can see that although the numbers are smaller, there is complete concordance — all 107 patients who had an SVR4 achieved an SVR24.... The concordance held, irrespective of the presence or absence of interferon. However, the dataset is fairly small in the noninterferon arm, limiting conclusions."

Dr. Lawitz concluded that "much of the concordance is due to the high response rates observed across all treatment groups. To date, relapse after week 4 is infrequent and was only observed in patients who received a peg-interferon-containing regimen."

Session moderator George Papatheodoridis, MD, associate professor of medicine and gastroenterology at the Medical School of Athens University, staff member at Hippokration General Hospital, in Athens, Greece, and a member of the European Association for the Study of the Liver Governing Board Scientific Committee, told Medscape Medical News that GS-7977 "is a very interesting, very promising molecule. It seems to be rather safe and very effective, even in combination with ribavirin." Dr. Papatheodoridis was not involved in any of the studies.

In terms of new drugs to treat HCV, he said, "some of the new molecules are very genotype-specific.... Most of the protease inhibitors are developed to work only for genotype 1; some of them work for genotype 2, but not 3 and 4. The nucleoside polymerase inhibitors seem to work better across almost all genotypes, so this is the only class [of drug] that is not that genotype-specific."

Dr. Papatheodoridis wondered about the use of SVR4 as a standard efficacy measure. "I don't think that SVR4 will and should be the standard for SVR," he told Medscape Medical News. "Of course, we know that the FDA and most of the physicians have now accepted SVR12. So probably...SVR12 is going to be the standard for reporting trials in the near future. Still, with all these combinations, patients should have at least 1 examination, maybe 6 months or 12 months after SVR12, so we can be sure that this SVR remains over time. I think that SVR12 is going to be the standard from now on, but the patients treated with the new regimens should be followed for a bit longer."

He admitted that SVR4 looks predictive of later sustained responses. "You expect most of the patients to relapse soon after stopping treatment [if they are going relapse]. Of course, SVR4 is reasonable; we know and we expect that it is going to be associated with SVR12 and SVR24. There is no rush to decide the SVR just 4 weeks after treatment.... We should be sure that we eradicated the virus," he cautioned.

Dr. Lawitz reports financial relationships with Abbott, Achillion Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, GlobeImmune, Idenix Pharmaceuticals, Idera Pharmaceuticals, Inhibitex Pharmaceuticals, Medarex, Medtronic, Merck, Novartis, Pharmasset, Roche, sanofi-aventis, Schering-Plough, Santaris Pharmaceuticals, Scynexis Pharmaceuticals, Tibotec, Vertex Pharmaceuticals, ViroChem Pharma, and ZymoGenetics. Dr. Papatheodoridis has disclosed no relevant financial relationships.

The International Liver Congress 2012: Abstract 7. Presented April 19, 2012.

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EASL 2012: [SLIDES] Once Daily GS-7977 Plus Ribavirin in HCV Genotypes 1-3: The ELECTRON Trial

Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Tel: (650)522-5373
Fax: (650)522-5260

Poster
Number 1113

47th Annual Meeting of the
European Association for the Study of the Liver
April 18 - 22, 2012
Barcelona, Spain

E. Gane1, C. Stedman2, R. Hyland3, R. Sorensen3, W. Symonds3, R. Hindes3, M. Berrey

1New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, 2Gastroenterology Department, Christchurch Hospital, Christchurch, New Zealand; 3Gilead Sciences, Foster City, CA

Introduction

• GS-7977 (formerly PSI-7977) is a potent, specifi c nucleotide analog developed
  for the treatment of patients chronically infected with hepatitis C virus (HCV)
• Safe and well tolerated in clinical studies
• Once daily, with or without food
• Potent antiviral activity
• High barrier to resistance

─ No virologic breakthrough to date

• We conducted a Phase 2 trial (ELECTRON) to evaluate the safety and effi cacy
  of GS-7977 and ribavirin (RBV) with and without pegylated interferon (PEG) in
  genotype (GT) 1-3 patients with chronic HCV infection
• Results from the fi rst 5 arms of ELECTRON using interferon-sparing/-free
  regimens in patients with HCV GT 2/3 and GT 1 prior null responders:1,2,3,4

─ SAFETY

• GS-7977 400 mg QD + RBV for 12 weeks was well tolerated with no
  attributable safety signal

─ POTENCY

• GS-7977 + RBV elicited rapid suppression of HCV RNA → 100% RVR
• All GT 2/3 treated with GS-7977 + RBV patients achieved SVR24
• Patients treated with GS-7977 monotherapy achieved 60% SVR24
• GT 1 prior null responders achieved 11% SVR4 with a 12-week GS-7977+
  RBV regimen
• No virologic breakthrough has been observed during treatment with
  GS-7977

Objective

To evaluate the safety and effi cacy of GS-7977 400 mg once daily in combination
with RBV with and without PEG in the following populations:

• Treatment-naïve GT 2/3 patients treated with GS-7977 + RBV + PEG for
  8 weeks
• Prior null responder GT 1 patients treated for 12 weeks with GS-7977 + RBV
• Treatment-naïve GT 1 patients treated for 12 weeks with GS-7977 + RBV
• Previously treated GT 2/3 patients treated for 12 weeks with GS-7977 + RBV

Methods

Figure 1. ELECTRON Study Design

• Null responders were defi ned as patients with <2 log10 IU/mL decline from
  baseline HCV RNA after at least 12 weeks of PEG and RBV
• Treatment-experienced patients were defi ned as those who had any of the
  following responses after at least 12 weeks of PEG and RBV:
  • <2 log10 IU/mL decline from baseline in HCV RNA
  • ≥2 log10 IU/mL reduction in HCV RNA, but HCV RNA >LOQ at end of
  treatment
  • HCV RNA <LOQ at end of treatment, but subsequent HCV RNA >LOQ
  (relapsers)

Results

Table 1. Baseline Patient & Disease Characteristics

Figure 2. On-treatment Viral Suppression

Table 2. Patients with HCV RNA <LOD Over Time, n/N (%)

*1 subject relapsed at the SVR8 time point after having previously achieved SVR4

Table 3. Safety and Tolerability

*SAEs considered unrelated to GS-7977
†In >1 patient treated with GS-7977; no Grade 3 or 4 AEs occurred in treatment arms lacking PEG

Resistance Data:

• Population sequencing has been completed in 5 of 8 relapsers from the GT-1
  prior null responder arm: no S282T was found
• Deep sequencing did not identify any S282T-containing mutants

Table 4. Grade 3 or 4 Laboratory Abnormalities in >1 Patient

Conclusions

• 88% of treatment-naïve GT 1 patients achieved SVR4 following 12 weeks of therapy with GS-7977 + RBV
  ─ This result suggests that 12 weeks of GS-7977 + RBV can potentially provide higher rates of SVR in treatment-naïve GT 1 patients than those achieved with longer durations of PI + PEG/RBV
• The combination of GS-7977 + RBV was well tolerated in all genotypes regardless of prior treatment history
• No virologic breakthrough occurred in any arm, suggesting a high barrier to resistance
  ─ To date, the S282T mutation has not been seen in any GS-7977/RBV regimen
• These results where GS-7977 400 mg once daily (QD) is being utilized in a variety of regimens and populations further demonstrate the utility of GS-7977 across a broad spectrum of HCV disease treatment

References and Acknowledgements

1. Lawitz E, et al. J Hepatol 2011;54:S543.
2. Gane E, et al. AASLD 2011
3. Gane E, et al. APASL 2012
4. Gane E, et al. CROI 2012

Thanks to all the patients and their families and:
• Christian Schwabe, Vithika Suri, ACS
• Catherine Stedman, Richard Robson, CCS

© 2012 Gilead Sciences

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Have BMS and Gilead found the 'killer app' for hep. C?

Marc Iskowitz

April 19, 2012

Scientists are getting closer to finding the killer app in treating hepatitis C, but it may be too soon to pick a winner.

Bristol-Myers Squibb and Gilead said this morning that an all-oral therapy joining together two drugs the companies are each developing suppressed the virus in more than 95% of patients across a broad spectrum of genotypes.

The drug combo of daclatasvir from BMS and Gilead's GS-7977 reached a 100% sustained virologic response (SVR), or cure rate, at week four in one common subgroup, genotype 1 patients who have not been previously treated with interferon—an injectable associated with flu-like side effects.

The 100% cure rate held even when ribavirin, another traditional mainstay of treatment, was left out of the mix, bettering a roughly 90% SVR rate seen for an Abbott triple therapy in a trial a few weeks ago.

“It obviously doesn't get any better than this,” cheered ISI analyst Mark Schoenebaum in a quick note to investors this morning after BMS and Gilead announced their results. Data from the Phase II combo trial are “best case,” he added, in that only 2% of respondents to an informal survey he fielded earlier this month said they expected the 100% SVR rate.

The findings accelerated momentum in an already fast-moving category, in which drugmakers are swooping up assets to pad HCV pipelines and experimenting with a variety of regimens and combinations. Last November Gilead agreed to pay almost $11 billion for biotech firm Pharmasset's GS-7977, and BMS in January said it was buying Inhibitex for about $2.5 billion and getting access to that firm's potential HCV drug, INX-189.

The direct-acting antivirals (DAAs) from BMS, Gilead and Abbott are showing the best efficacy and tolerability to date.

Not that there haven't been speed bumps along the way. In February, Gilead's ‘7977 had come under assault when data showed that six out of six subjects treated with the pipeline drug, who were prior null responders to other HCV therapy, had experienced a relapse of their disease.

Analysts had predicted that patients who are naïve to therapy would be easier to treat with a non-interferon regimen than null responders, and the Gilead/BMS data furthered this notion. Several analysts now believe daclatasvir, an NS5a inhibitor, and ‘7977, a nucleotide analog (or “Nuc” as the class is called), may form the best treatment “backbone” option across all genotypes.

“It appears that the ‘killer app' in HCV is probably an NS5A plus a nuc without ribavirin,” Schoenebaum declared.

The newer protease inhibitors—Vertex's Incivek and Merck's Victrelis, both launched in 2011—look like they will be vulnerable to the all-oral regimens, but not for a few years.

“These results obviously reinforce the expectation that DAA-only (IFN and RBV-sparing) regimens will likely quickly supplant current HCV treatments when they become available in the 2015/2016 timeframe,” wrote Deutsche Bank's Barbara Ryan in a note today.

In a Thursday dispatch to investors, Credit Suisse's Catherine Arnold said the data also “takes a little shine off” Abbott's HCV program, “but we still view it as a competitive presence.” The triple therapy combines the firm's protease inhibitor ABT-450 + non-nucleoside polymerase inhibitor ABT-333 + ribavirin.

While the Gilead/BMS combination sets the bar high for competitors, scientists are still debating where the best treatment synergy lies, and firms are awaiting more data before finalizing their commercial plans.

The Gilead/BMS combo “represents the most compelling all-oral, interferon-free data in the highly visible [HCV] marketplace,” noted Arnold. “Despite this strong data,” she added, “a partnership is unlikely in the near term as both companies wait for additional data sets related to their HCV assets to fully evaluate their options.”

Ryan cautioned that other factors—side effects, dosing convenience and, of course, cost—“will be important considerations in determining market share. In our opinion, it is premature to conclude who the ultimate winners and losers will be in the ‘new' HCV market on the basis of the data available to date.” Ryan doesn't think any one or two players will dominate the field. Null and non-responders could also be a factor in determining long-term HCV dominance.

Results from a cocktail joining Gilead's ‘7977 and ribavirin also surprised, hitting an SVR rate of 88%—far better than the 50% the Street had expected, according to Schoenebaum. Abbott's all-oral triple combo may be another good backbone option, while daclatasvir so far looks like a solid add-on option—one that has pan-genotype efficacy and excellent tolerability—and BMS is exploring multiple pairing options (including with its own Nuc, INX-189).

Other Nucs in development include Vertex's ALS-2200 and ALS-2158, and biotech firm Idenix's IDX184, which can be combined with its NS5A inhibitor, IDX719.

Source

Also See:

1. Collaboration on Hepatitis Drugs Lags
2. Gilead, Bristol Put Profits Ahead of Best Care for Hep C Patients

Collaboration on Hepatitis Drugs Lags

David Paul Morris/Bloomberg News

A machine purifying a drug at a Gilead Sciences laboratory in California.

By ANDREW POLLACK

Published: April 19, 2012

A combination of two pills proved extremely effective in treating hepatitis C in a small trial, raising hopes among researchers that the disease will be curable without an injected drug that has debilitating side effects.

But the combination might not find its way to the market because one pill is owned by Gilead Sciences and the other by Bristol-Myers Squibb. The companies have not agreed to collaborate, to the chagrin of some doctors.

“The only appropriate motivation should be what is the best and fastest way to get cures, not what is best for the shareholders,” said Dr. Scott Friedman, chief of liver diseases at the Mount Sinai School of Medicine in New York, who was not involved in the trial.

Dr. Douglas J. Manion, a senior vice president for Bristol-Myers, said his company was “keen” on working with Gilead but that “thus far, they have been unwilling to engage in that collaboration.”

Norbert W. Bischofberger, executive vice president for research and development at Gilead, said his company wanted to wait several months for data on other treatment options before deciding what path to take.

“We told them it’s too early to jump wildly into this collaboration,” he said.

Both executives spoke separately by telephone from the International Liver Congress in Barcelona, Spain, where data on the drug combination was presented.

Gilead and Bristol are among the leaders of one of the most heated races in the pharmaceutical industry — to develop an all oral treatment for hepatitis C, a liver-damaging virus that infects three million to four million Americans.

New pills introduced last year by Vertex Pharmaceuticals and Merck have sharply improved the cure rate, to about 60 to 80 percent. But those drugs must still be used alpha interferon, which is injected weekly for up to a year and can cause flulike symptoms.

Many companies are trying to develop combinations of pills — similar to those used to treat H.I.V. — that would eradicate the virus without the need for interferon.

Results from several companies presented at the Barcelona conference have given doctors confidence that this will indeed be possible, with the first such combinations reaching the market perhaps by 2014.

Dr. Melissa Palmer, who was a practicing liver specialist until last fall, said that the trials were small and patients were usually not followed long enough to see if they were truly cured.

“It’s going to be important to wait a longer time to see if these results are sustainable,” said Dr. Palmer, who is now a consultant to investors.

Nonetheless, investors were busily predicting from the Barcelona data which companies will capture the billions of dollars a year in possible sales. Besides Gilead and Bristol, some mentioned Abbott Laboratories, which also presented strong preliminary data.

Gilead, a leader in drugs for AIDS, paid $11 billion a few months ago to acquire Pharmasset, based on very preliminary data on its hepatitis drug, now called GS-7977. Subsequent data was not as good and Gilead’s stock sank.

But the data announced on Thursday appeared to restore confidence in 7977. Shares of Gilead gained 12 percent to $52.25. Shares of Bristol rose 1 percent to $33.93.

All 29 of the patients with the strain of the virus that is most common in the United States had no detectable virus in their blood four weeks after finishing 24 weeks of treatment with GS-7977 and Bristol’s pill, daclatasvir. The figure was 28 out of 30 patients with two other virus strains. Each pill was taken once a day.

Doctors usually wait 12 to 24 weeks after finishing treatment to declare a cure, since there can be relapses.

Dr. Bischofberger said that before deciding whether to work with Bristol on a larger trial, Gilead wanted to wait a few months for data showing whether the same two drugs would work with only 12 weeks of treatment instead of 24.

He said he also wanted to see whether Gilead could improve results of using GS-7977 with ribavirin, a drug that is part of the existing treatment.

A combination of GS-7977 with ribavirin, which is generic, would be far less expensive than a combination with daclatasvir, he said, because new hepatitis drugs are expected to cost tens of thousands of dollars for a course of treatment.

A combination with ribavirin would also mean that Gilead would not have to split revenues with Bristol, making it easier to recoup the money it spent to buy Pharmasset.

Dr. Bischofberger said that once both 7977 and daclatasvir won approval, doctors could use them together, so patients would not be shortchanged if the companies did not collaborate.

Source

Also See: Gilead, Bristol Put Profits Ahead of Best Care for Hep C Patients

Novel Drug Works Against Hepatitis C

By Todd Neale, Senior Staff Writer, MedPage Today

Published: April 19, 2012

Take Posttest

The investigational drug GS-7977 performed well against hepatitis C virus (HCV) in treatment-naive patients, with or without contributions from pegylated interferon and ribavirin, several studies showed.

In a phase II study, GS-7977 (a nucleotide NS5B inhibitor) combined with daclatasvir (a novel NS5B inhibitor) resulted in rapid and sustained viral responses in patients infected with HCV genotypes 1, 2, or 3, Mark Sulkowski, MD, of Johns Hopkins University, reported at the European Association for the Study of the Liver meeting in Barcelona.

And in another phase II study, presented by Kris Kowdley, MD, of Virginia Mason Medical Center in Seattle, GS-7977 combined with pegylated interferon and ribavirin showed similar efficacy in patients with HCV genotype 1, the hardest-to-treat strain.

GS-7977 and daclatasvir are two of several new drugs being developed that directly target HCV, with the aim of moving away from the use of pegylated interferon and ribavirin, which boost the immune system to battle the virus but come with multiple side effects. Those include flu-like symptoms, depression, neutropenia, thrombocytopenia, and anemia.

In the study presented by Sulkowski, treatment-naive patients with HCV genotype 1, 2, or 3 were randomized to one of three arms:

• Daily GS-7977 400 mg for 7 days followed by GS-7977 plus daily daclatasvir 60 mg for 23 weeks
• Daily GS-7977 and daclatasvir for 24 weeks
• Daily GS-7977 and daclatasvir plus ribavirin for 24 weeks

The 44 patients with genotype 1 were randomized separately from the 44 with genotypes 2 and 3.

By week four of treatment, all patients had a sustained viral response. That figure was no lower than 86% in any group at the end of treatment and at four weeks after the end of treatment.

Ribavirin did not accentuate the virologic response.

The treatment was relatively well tolerated, and the most frequent adverse events were fatigue, headache, and nausea. Grade 3/4 laboratory abnormalities included elevated cholesterol in one patient, elevated glucose in two, low hemoglobin in six, lymphopenia in one, and low phosphorus in two.

The study presented by Kowdley -- the ATOMIC study -- included 316 patients with HCV genotype 1, 11 with genotype 4 and five with genotype 6. They were noncirrhotic, were treatment-naive, and had an HCV RNA of at least 50,000 IU/mL. There were three treatment arms:

• Daily GS-7977 400 mg plus pegylated interferon (180 µg weekly injection) and ribavirin (500 mg twice daily) for 12 weeks
• Daily GS-7977 400 mg plus pegylated interferon and ribavirin for 24 weeks
• Daily GS-7977 400 mg plus pegylated interferon and ribavirin for 12 weeks, with re-randomization at week 12 to GS-7977 alone or GS-7977 plus ribavirin for the rest of the study

By week two of treatment, 78% had HCV RNA below the level of detection, and 97% achieved a rapid viral response (HCV RNA undetectable after 4 weeks of treatment).

At 4 weeks after treatment ended, 92% of patients had a sustained viral response.

Among the patients randomized to the 12-week treatment arm, 90% achieved a sustained virologic response 12 weeks after treatment ended.

As in the other study, GS-7977 was generally well tolerated with adverse events consistent with the safety profile of interferon and ribavirin. Side effects included fatigue (54%), nausea (29%), headache (29%), chills (19%), and insomnia (19%).

Source

Also See:

1. EASL 2012: All-Oral Combination of Investigational Hepatitis C (HCV) Compounds Daclatasvir and GS-7977 Achieved Sustained Virologic Response (SVR4) in 100% of Genotype 1 and 91% of Genotype 2 and 3 Treatment-Naïve Patients in Phase II Study
2. EASL 2012: Gilead Announces Sustained Virologic Response Data for 12-Week Regimen of GS-7977 Plus Pegylated Interferon and Ribavirin in Genotype 1 Hepatitis C Patients

EASL 2012: Dramatic data for Gilead, Bristol hepatitis C drugs

Bill Berkrot Reuters

8:57 a.m. CDT, April 19, 2012

(Reuters) - A combination of experimental hepatitis C drugs from Gilead Science Inc and Bristol-Myers Squibb Co showed impressive results in new clinical trial data released on Thursday, helping fuel a 16 percent rise in Gilead shares.

In the mid-stage trial, Gilead's GS-7977, acquired with its $11 billion purchase of Pharmasset, was combined with Bristol's daclatasvir and received very strong response rates from previously untreated patients.

The results were accomplished without using interferon, an injected drug that causes flu-like symptoms and other side effects that often lead hepatitis C patients to discontinue or delay treatment.

"This reinforces that ‘7977 is the best asset in the Hep C space and restores 'world order' with Gilead ... as the one to beat," Thomas Russo, analyst at Robert W. Baird, said in a research note.

Bristol shares rose 3.3 percent in early trading.

Bristol's daclatasvir is from a new class of drugs known as NS5A inhibitors. GS-7977 is a closely watched hepatitis C drug known as a nucleotide polymerase inhibitor.

All 44 of the patients in the study who had the most common and difficult to treat Genotype 1 version of the disease had undetectable levels of the virus in their blood four weeks after completing treatment, for a 100 percent response rate.

Forty of 44 patients with Genotypes 2 or 3 of the virus had undetectable levels at four weeks following treatment for a 91 percent response rate.

Any patient who still has undetectable levels of the virus 12 weeks after completing treatment, known as a sustained viral response, or SVR12, is considered cured of the serious liver disease.

Separately, Gilead reported results from the ELECTRON study, showing that of 25 patients with genotype 1 hepatitis who completed 12 weeks of treatment with GS-7977 and the older antiviral ribavirin (RBV), 88 percent still had undetectable levels of virus four weeks after completion of treatment.

Mark Schoenebaum, an analyst at ISI Group, said the ELECTRON data was better than expected, since most analysts had expected a result around 50 percent.

"Overall, we'd characterize the phase 2 data as very robust, with SVR rates well above expectations," J.P. Morgan analyst Geoff Meacham said in a research note.

DEVELOPMENT RACE

Hepatitis C is currently one of the hottest areas of medical research, with several companies pursuing treatment regimens that would eliminate the need for interferon. Even the newest hepatitis C drugs approved last year that dramatically improved cure rates must be taken with interferon and ribavirin.

Patients in the various arms of the Bristol-Gilead study were treated for 24 weeks. The interim data looked at the response rates four weeks after they completed the therapy, which is considered to be a fairly accurate predictor of the likely final results.

In one arm of the study, the Gilead drug was given alone for the first week as a lead in therapy. Another arm added the older antiviral drug, ribavirin, which is currently part of all hepatitis C treatment regimens.

Researchers found that using GS-7977 as a lead in drug did not impact response rates and that the addition of ribavirin made no difference other than to add side effects, such as anemia, that were not seen in the non-ribavirin arms of the study, Bristol-Myers said.

One patient in the Genotype 2/3 arm experienced viral breakthrough during treatment and one suffered a relapse. Two patients dropped out for medical reasons believed to be unrelated to the study drugs, according to the data presented on Thursday at a major European liver disease meeting in Barcelona.

The experimental drugs were considered to be well tolerated with the most frequent side effects being fatigue, headache and nausea, Bristol said.

Gilead is commencing a trial of 7977 in combination with its own experimental NS5A inhibitor, while Bristol-Myers is also testing daclatasvir in combination with a drug similar to 7977 that it acquired with its $2.5 billion purchase of Inhibitex, as well as with other experimental drugs in its development pipeline.

(Additional reporting by Michele Gershberg in New York and Ben Hirschler in London; Editing by Andre Grenon, Dave Zimmerman)

Source

EASL 2012: Gilead Announces Early Sustained Virologic Response Rates for GS-7977 Plus Ribavirin in Genotype 1 Treatment-Na ïve Hepatitis C Patients

- Interim Results Reported from ELECTRON and QUANTUM Studies -

BARCELONA, Spain, Apr 19, 2012 (BUSINESS WIRE) --Gilead Sciences, Inc. (Nasdaq: GILD) today announced interim data from the Phase 2 ELECTRON study examining the investigational once-daily oral agent GS-7977 plus ribavirin (RBV) in treatment-naïve patients with genotype 1 chronic hepatitis C virus (HCV) infection. Of the 25 patients who completed 12 weeks of treatment with the GS-7977-based regimen, 88 percent of patients (n=22/25) remained HCV RNA undetectable four weeks after completion of treatment. Three patients experienced viral relapse. These findings are being presented this week during a poster session (Poster #1113) at the 47^th Annual Meeting of the European Association for the Study of the Liver (International Liver Congress 2012) in Barcelona, Spain.

"These preliminary results suggest that 12 weeks of therapy with once-daily oral GS-7977 and ribavirin may be enough to cure hepatitis C in many genotype 1 patients, including those who are currently not candidates to receive interferon," said Professor Edward Gane, MD, Deputy Director and Hepatologist, New Zealand Liver Transplant Unit, Auckland City Hospital in New Zealand, and principal investigator of the ELECTRON study. "Further investigation of GS-7977 in a variety of patient populations and combinations will be important in assessing the drug's potential as part of an all-oral regimen for hepatitis C."

Results from three additional arms of the ELECTRON study examining GS-7977-based therapy in various patient populations are also being presented this week at the International Liver Congress. These include null responder genotype 1 patients, and genotype 2 and genotype 3 patients, both treatment-naïve and prior non-responders.

Overall, GS-7977 was well tolerated and exhibited a favorable safety profile. No patients experienced viral rebound during treatment. No patients discontinued therapy due to an adverse event. The most common adverse events were fatigue, dizziness and headache, and two grade 3/4 laboratory abnormalities were reported.

Gilead today also announced interim results from a second Phase 2 trial (QUANTUM) examining a 12- and 24-week duration of GS-7977 plus RBV in treatment-naïve patients. Twenty-five patients were randomized to the 12-week treatment arm: 19 genotype 1 patients; four genotype 3 patients; and two genotype 2 patients. Two genotype 1 patients discontinued therapy prematurely during the 12-week treatment period. At the four-week post-treatment time period, data were available for 17 genotype 1 patients. Of these, 10/17 (59 percent) remained HCV RNA undetectable. Seven patients (41 percent) experienced viral relapse. Additionally, seven of the patients who have reached the eight week post-treatment time period, and who achieved SVR4, remain HCV RNA undetectable.

The overall safety and efficacy profile of GS-7977 was consistent with that seen in ELECTRON. No patients experienced viral rebound while on treatment and no patients discontinued therapy due to an adverse event.

Eleven of the 25 patients (44 percent) in ELECTRON and three of 19 patients (16 percent) in QUANTUM had the IL28B C/C genetic polymorphism. Each of the three patients who relapsed in the ELECTRON study had a different IL28B polymorphism (C/C, C/T or T/T). The seven patients who relapsed in the QUANTUM study either had IL28B C/T (n=4) or IL28B T/T (n=3) genetic polymorphisms. Patients in both studies will continue to be observed to determine sustained virologic response rates at weeks 12 and 24 of follow-up (SVR12 and SVR24).

"The early results from these studies confirm that GS-7977 has the potential to become the cornerstone of an efficacious, all-oral combination regimen for many patients with chronic hepatitis C infection," said John McHutchison, MD, Senior Vice President, Liver Disease Therapeutics, Gilead Sciences. "We look forward to more data unfolding as our trials progress and we expect to initiate additional studies with GS-7977 in combination with other oral antivirals in our pipeline in the coming months. Our goal is to develop a short, simple, safe and effective single tablet regimen for HCV patients throughout the world."

About ELECTRON

ELECTRON is an ongoing Phase 2 randomized open-label clinical study evaluating GS-7977 for the treatment of chronic HCV infection. The primary endpoint of the trial is the safety and tolerability of GS-7977 400 mg once-daily for 8 or 12 weeks, with and without RBV and/or Peg-IFN in HCV patients with genotypes 1, 2 or 3. Study populations include treatment-naïve non-cirrhotic patients and those who have failed prior interferon based therapies or "null" responders.

About QUANTUM

QUANTUM is a Phase 2 randomized double-blind placebo-controlled clinical study evaluating GS-7977 for the treatment of chronic HCV infection. The current active arms of the trial are examining GS-7977 400 mg once-daily plus RBV for 12 or 24 weeks in cirrhotic and non-cirrhotic treatment-naïve HCV patients with genotypes 1, 2 and 3. The results announced today are for the cohort of patients who have received and completed 12 weeks of therapy with GS-7977 plus RBV (n=25).

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 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 possibility that the proportion of patients who maintain a sustained virologic response 12 and 24 weeks post-treatment will not be as favorable as the sustained virologic response rates reported in this press release and the possibility of unfavorable results from additional arms of the ELECTRON and QUANTUM studies and subsequent clinical trials involving GS-7977 and RBV. As a result, GS-7977, including in combination with other oral antivirals in Gilead's pipeline, may never be successfully commercialized. Further, Gilead may make a strategic decision to discontinue development of the compounds if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. In addition, Gilead may be unable to develop an all-oral antiviral regimen for HCV genotype 1 patients or a pangenotypic regimen for all HCV patients. 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 detail in Gilead's Annual Report on Form 10-K for the year ended December 31, 2011, 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 or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

SOURCE: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Susan Hubbard, 650-868-5215 (Investors)
shubbard@gilead.com
Patrick O'Brien, 650-522-1936 (Investors)
pobrien@gilead.com
Cara Miller, 650-576-7849 (Media)
cmiller@gilead.com

Source

EASL 2012: Gilead Announces Sustained Virologic Response Data for 12-Week Regimen of GS-7977 Plus Pegylated Interferon and Ribavirin in Genotype 1 Hepatitis C Patients

- ATOMIC Data Demonstrate High Cure Rates in Genotype 1 Patients With 12 Weeks of Treatment -

BARCELONA, Spain, Apr 19, 2012 (BUSINESS WIRE) --Gilead Sciences, Inc. (Nasdaq:GILD) today announced interim data from a Phase 2 trial (ATOMIC) examining a 12-week course of treatment with the once-daily nucleotide GS-7977 plus pegylated interferon (Peg-IFN) and ribavirin (RBV) in treatment-naïve patients with genotype 1 chronic hepatitis C virus (HCV) infection. The study found that 90 percent of patients (n=47/52, missing data equals failure analysis) achieved a 12-week sustained virologic response (SVR12), defined as maintaining undetectable viral load (HCV RNA <25 IU/mL) 12 weeks after the completion of therapy. These findings will be presented today during an oral session at the 47^th Annual Meeting of the European Association for the Study of the Liver (International Liver Congress 2012) in Barcelona, Spain.

"These data suggest that this GS-7977-based regimen could offer most patients with genotype 1 a simple, short, three-month course of treatment with very high cure rates," said Kris Kowdley, MD, Director of the Liver Center of Excellence at the Virginia Mason Medical Center in Seattle and the study's principal investigator. "An all-oral regimen for HCV remains the ultimate treatment goal. In the interim, these results suggest that we may soon be able to end the complex process of response-guided HCV therapy and shorten the duration of treatment, which would be a significant advance for patients and for physicians who manage their care."

In this study, 52 patients were randomized to the 12-week treatment arm. One patient was lost to follow up during the course of treatment. At the end of treatment, 51/51 patients (100 percent) were HCV RNA undetectable. At the 12-week, post-treatment time period, data were available for 50/51 patients, as one patient was lost to follow up during the post-treatment time period. Of the 50 patients, 47 (94 percent) remained HCV RNA undetectable. Three patients experienced viral relapse after the end of treatment.

Overall, GS-7977 was well tolerated. The frequency and severity of adverse events were consistent with the historical safety profile of Peg-IFN and RBV and included fatigue, headache, nausea, chills and insomnia.

About ATOMIC

ATOMIC is an ongoing Phase 2 randomized open-label clinical trial evaluating the efficacy, safety and tolerability of a regimen containing GS-7977 (400 mg once daily), Peg-IFN (180 ug weekly injection) and RBV (500 mg twice daily) for the treatment of chronic HCV infection in treatment-naïve patients. Patients with genotype 1 HCV (n=316) who were non-cirrhotic and had HCV RNA of at least 50,000 IU/mL were randomized (1:2:3) to receive the regimen for 12 weeks (n=52), 24 weeks (n=109) or 12 weeks followed by re-randomization (1:1) to receive an additional 12 weeks of either GS-7977 alone or GS-7977 plus RBV (n=155). Additionally, 16 patients with HCV genotypes 4 and 6 received the 24-week regimen of GS-7977, Peg-IFN and RBV.

Four-week response rates following completion of therapy from two additional arms of ATOMIC also were presented at the International Liver Congress. Patients in all arms of the study will be followed to determine their 12- and 24-week sustained virologic response rates.

Additional information about the study can be found at www.clinicaltrials.gov. GS-7977 is an investigational product and its safety and efficacy has not yet 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 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 possibility that the proportion of patients who maintain a sustained virologic response 24 weeks post-treatment will not be as favorable as the sustained virologic response rates reported in this press release and the possibility of unfavorable results from additional arms of the ATOMIC study and subsequent clinical trials involving GS-7977 plus Peg-IFN and RBV. As a result, GS-7977 may never be successfully commercialized. In addition, Gilead may make a strategic decision to discontinue development of GS-7977 if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. Further, Gilead may be unable to develop an all-oral antiviral regimen for HCV genotype 1 patients or a pangenotypic regimen for all HCV patients. 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 detail in Gilead's Annual Report on Form 10-K for the year ended December 31, 2011, 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 or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000 .

SOURCE: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Susan Hubbard, 650-868-5215 (Investors)
shubbard@gilead.com
Patrick O'Brien, 650-522-1936 (Investors)
pobrien@gilead.com
Cara Miller, 650-576-7849 (Media)
cmiller@gilead.com

Source

EASL 2012: Gilead Sciences to Present New Hepatitis B and C Data at European Conference on Liver Disease This Week

- Presentations Include First Results For Lead Hepatitis C Candidate GS-7977 In Treatment-Naïve Genotype 1 Patients -

BARCELONA, Spain, Apr 18, 2012 (BUSINESS WIRE) --Gilead Sciences, Inc. (Nasdaq:GILD) today announced that 30 abstracts examining the company's products and investigational agents for hepatitis B and C have been selected for presentation at the 47^th Annual Meeting of the European Association for the Study of the Liver (International Liver Congress 2012) taking place April 18-22 in Barcelona, Spain. The abstracts describe clinical and preclinical data for a number of investigational chronic hepatitis C compounds, as well as new long-term data for Viread^(R) (tenofovir disoproxil fumarate) for chronic hepatitis B.

Presentations will include data from several studies examining Gilead's late-stage nucleotide analog polymerase inhibitor, GS-7977, in treatment-naïve genotype 1 hepatitis C patients. Genotype 1 is the most prevalent strain of the hepatitis C virus (HCV), and also the hardest to treat with existing therapies. Data from ELECTRON (Poster #1113) and ATOMIC (Oral Abstract #1) will be presented and both studies have been selected for inclusion in official EASL Press Office activities.

In addition to GS-7977, Gilead is advancing multiple oral compounds with different mechanisms of action with the goal of creating an efficacious, well tolerated and convenient all-oral treatment regimen for chronic HCV. Notably, data will be presented for two of these compounds, GS-5885 (an NS5A inhibitor) and GS-9669 (a non-nucleoside polymerase inhibitor):

• Interim efficacy and safety results for a Phase 2 study (Study 120) examining 12 weeks of treatment with GS-5885, GS-9451, tegobuvir (GS-9190) and ribavirin. Based on the results of this trial and other studies involving more than 800 patients treated with GS-5885 for at least 12 weeks, Gilead has selected a 90 mg dose of GS-5885 for further clinical development (Latebreaker Poster #1421).
• Results of a three-day, Phase 1, ascending-dose study, which demonstrate the potent antiviral activity of GS-9669, a non-nucleoside polymerase inhibitor, when administered once-daily (Poster #1189).

Seven abstracts at the International Liver Congress will highlight the safety and efficacy profile of Viread, the most-prescribed treatmentfor chronic hepatitis B in the United States and major countries of Europe. Notably, new data further characterize Viread's well-established renal safety profile:

• The VIREAL prospective cohort study reports on 115 chronic hepatitis B patients with reduced renal function at baseline, the majority of whom either remained stable or improved after 48 weeks of treatment with Viread (Poster #531).

Abstracts for Gilead's presentations can currently be accessed on the EASL website, with the exception of the ELECTRON and ATOMIC studies, which are embargoed until Thursday, April 19, 2012 due to their inclusion in the press program of the International Liver Congress. Gilead will issue press releases describing the data from these studies. Further information about these studies can also be found at www.clinicaltrials.gov.

GS-7977, GS-5885, GS-9669, GS-9451 and tegobuvir (GS-9190) are investigational products and their safety and efficacy have not yet been established.

Important Information About Viread for Chronic Hepatitis B

Viread (tenofovir disoproxil fumarate) is indicated for the treatment of chronic hepatitis B in adults. The following points should be considered when initiating therapy with Viread for the treatment of HBV infection: This indication is based primarily on data from the treatment of nucleoside-treatment-naïve patients, and a smaller number of patients who had previously received lamivudine or adefovir. Patients were adults with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver disease. Viread was evaluated in a limited number of subjects with chronic hepatitis B and decompensated liver disease. The number of patients in clinical trials who had lamivudine- or adefovir-associated substitutions at baseline was too small to reach conclusions of efficacy.

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleos(t)ide analogs, including Viread, in combination with other antiretrovirals.

Severe acute exacerbations of hepatitis have been reported in HBV-infected patients who have discontinued anti-hepatitis B therapy, including Viread. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including Viread. If appropriate, resumption of anti-hepatitis B therapy may be warranted.

New onset or worsening of renal impairment including cases of acute renal failure and Fanconi syndrome has been reported with the use of Viread. It is recommended to assess creatinine clearance (CrCl) before initiating treatment with Viread and monitor CrCl and serum phosphorus in patients at risk, including those who have previously experienced renal events while receiving Hepsera^(R). Administering Viread with concurrent or recent use of nephrotoxic drugs should be avoided.

Viread should not be used with other tenofovir-containing products (e.g., Atripla^(R), Complera^(R), Truvada^(R)). Viread should not be administered in combination with Hepsera.

Due to the risk of development of HIV-1 resistance, Viread should only be used as part of an appropriate antiretroviral combination regimen in HIV-infected patients with or without HBV coinfection. HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with Viread.

Decreases in bone mineral density (BMD) have been observed in HIV-infected patients. It is recommended that BMD monitoring be considered for patients with a history of pathologic fracture or who are at risk for osteopenia. The bone effects of Viread have not been studied in patients with chronic HBV infection. Cases of osteomalacia (associated with proximal renal tubulopathy and which may contribute to fractures) have been reported in association with the use of Viread.

In controlled clinical trials in patients with chronic hepatitis B with compensated liver disease, the most common adverse reaction (all grades) was nausea, observed in 9 percent of patients taking Viread at week 48. Other adverse reactions observed at week 48 in greater than 5 percent of patients treated with Viread include abdominal pain, diarrhea, headache, dizziness, fatigue, nasopharyngitis, back pain and skin rash.

In HBV-infected patients with decompensated liver disease, the most common adverse reactions (all grades) reported in greater-than or equal to 10 percent of patients treated with Viread were abdominal pain (22 percent), nausea (20 percent), insomnia (18 percent), pruritus (16 percent), vomiting (13 percent), dizziness (13 percent), and pyrexia (11 percent).

Coadministration of Viread with didanosine increases didanosine concentrations. Use with caution and monitor for evidence of didanosine toxicity (e.g., pancreatitis, neuropathy). Didanosine should be discontinued in patients who develop didanosine-associated adverse reactions. In adults weighing >60 kg, the didanosine dose should be reduced to 250 mg when it is coadministered with Viread. Data are not available to recommend a dose adjustment of didanosine for patients weighing <60 kg. Coadministration of Viread with atazanavir decreases atazanavir concentrations and increases tenofovir concentrations. Use atazanavir with Viread only with additional ritonavir; monitor for evidence of tenofovir toxicity. Coadministration of Viread with lopinavir/ritonavir increases tenofovir concentrations. Monitor for evidence of tenofovir toxicity.

The recommended dose for the treatment of chronic hepatitis B is 300 mg once daily taken orally without regard to food. The dosing interval of Viread should be adjusted and renal function closely monitored in patients with moderate and severe renal impairment.

The parent compound of Viread was discovered through a collaborative research effort between Dr. Antonin Holy, Institute for Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic (IOCB) in Prague and Dr. Erik DeClercq, Rega Institute for Medical Research, Katholic University in Leuven, Belgium.

Please see full Prescribing Information for Viread, Atripla, Complera, Truvada and Hepsera (including BOXED WARNINGS).

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 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 possibility of unfavorable subsequent results in studies examining GS-7977, GS-5885, GS-9669, GS-9451 and tegobuvir (GS-9190). As a result, these compounds may never be successfully commercialized. In addition, Gilead may make a strategic decision to discontinue development of these compounds if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. Further, Gilead may be unable to develop an all-oral antiviral regimen for HCV genotype 1 patients or a pangenotypic regimen for all HCV patients. 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 detail in Gilead's Annual Report on Form 10-K for the year ended December 31, 2011, 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.

U.S. full prescribing information for Viread is available at www.Viread.com.
U.S. full prescribing information for Atripla is available at www.Atripla.com.
U.S. full prescribing information for Complera is available at www.Complera.com.
U.S. full prescribing information for Truvada is available at www.Truvada.com.
U.S. full prescribing information for Hepsera is available at www.Hepsera.com.

Viread, Complera, Truvada and Hepsera are registered trademarks of Gilead Sciences, Inc.
Atripla is a registered trademark of Bristol-Myers Squibb & Gilead Sciences, LLC.

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

SOURCE: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Susan Hubbard, 650-868-5215 (Investors)
shubbard@gilead.com
Patrick O'Brien, 650-522-1936  (Investors)
pobrien@gilead.com
Cara Miller, 650-576-7849 (Media)
cmiller@gilead.com

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Gilead Sciences' Hepatitis Drug in Spotlight at Major Medical Meeting

By Brett Chase Apr 13, 2012 9:15 am

Both medical and investor communities will scrutinize results from an experimental, next-generation treatment for the liver-destroying virus hepatitis C.

It’s just about showtime for Gilead Sciences (GILD) and its experimental hepatitis C drug.

When specialist doctors from around the world gather in Spain next week to learn about new drugs in development for liver diseases, data for Gilead’s GS-7977 will be closely scrutinized and among the most anticipated research presented. The company hopes to show it has a real potential winner of a drug to treat the liver-wasting virus hepatitis C.

The big medical meeting, the International Liver Conference, begins Wednesday, and some scientific abstracts have been released in advance of the five-day gathering. However, a pair of key studies for Gilead’s drug are still embargoed until presentations starting Thursday. Gilead and a host of rivals are trying to develop an all-oral and better treatment regimen for hepatitis C. There has been a lot of excitement in the medical community and the investment world over Gilead’s drug.

“We have very high expectations for GS-7977,” Stifel Nicolaus analyst Joel Sendek says in a recent note recommending Gilead’s stock.

He is counting on the drug to spur future growth. Gilead is so dominant among HIV drug makers (with about 70% of the treatment market) that it’s unlikely to expand as rapidly in the future, he says.

Gilead also begins losing patent protection on HIV drugs later this decade, which is a key reason the company is expanding into hepatitis. A better hepatitis treatment potentially would bring in billions of dollars in new annual revenue. Gilead clearly has high hopes for 7977 as it was the strategic drug acquired with the recent $11 billion takeover of Pharmasset. (See Gilead Plans $11 Billion Takeover of Pharmasset to Gain Hepatitis Drugs.)

Shares of Gilead are up 12% this year but fell earlier this week. The stock closed at $45.72 Thursday.

While there are a number of other companies vying for the next generation of hepatitis C treatments, none of them made such a big wager on an acquisition. Among the other companies racing to bring a new hepatitis drug to market: Abbott Laboratories (ABT), Bristol-Myers Squibb (BMY), Merck (MRK), Vertex Pharmaceuticals (VRTX), Idenix Pharmaceuticals (IDIX) and Roche (RHHBY.PK). Abbott was among the companies whose hepatitis research was released earlier in advance of the Spain conference and turned some heads with impressive study data. (See Abbott Laboratories Rises to Record High on Hepatitis Drug Study.) A Bristol-Myers drug is being tested with Gilead’s 7977 in research to be presented at the medical meeting.

Hepatitis C is being carried by millions of people and many of them don’t even know they have the virus. As many as 170 million people worldwide have a chronic infection, according to one estimate. More than 3 million Americans are estimated to be chronically infected, according to government figures.

Vertex and Merck launched two much improved treatments for the virus last year.

The research focus now is to create a new class of drugs.

Twitter: @brettchase

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