AASLD-New Data from from AbbVie's Study, ABT-450 Containing Regimen

Related:
AbbVie’s two-drug, interferon-free combination cures genotype 1b hepatitis C infection in 95%
AbbVie is already testing ABT-450, an HCV protease inhibitor boosted by ritonavir, and ABT-267, an Ns5A inhibitor, in several phase III studies in combination with a third drug, the non-nucleoside polymerase inhibitor ABT-333. These trials will begin to report results by the end of 2013, and it is likely that AbbVie will submit a licensing application in early 2014 for this three-drug, interferon-free combination in order to achieve marketing approval in the second half of 2014.....

New Data from from AbbVie's Study, ABT-450 Containing Regimen

WATERTOWN, Mass.--(BUSINESS WIRE)--

Enanta Pharmaceuticals, Inc., (NASDAQ: ENTA  a research and development-focused biotechnology company dedicated to creating small molecule drugs in the infectious disease field, today announced that additional data from AbbVie's M13-393 study, referred to as PEARL-I, will be presented in an oral presentation at 5:15 p.m. ET today at The Liver Meeting, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, D.C.

In PEARL-I, SVR12 rates of 95% (40/42) in hepatitis C (HCV) GT-1b treatment-naïve patients and 90% (36/40) among prior null responders will be presented in this intent-to-treat analysis. Two patients in the treatment-naive arm did not achieve SVR12 due to loss to follow up. In the null responder arm, one patient experienced breakthrough and three patients relapsed.

PEARL-I is a phase-2b, interferon-free, 320 patient study being conducted by AbbVie to evaluate the once-daily, two-DAA regimen consisting of ABT-450/r (protease inhibitor plus ritonavir) + ABT-267 (AbbVie's NS5A inhibitor) in HCV treatment-naïve patients and treatment-experience patients. GT-1b treatment arms are ribavirin-free and also include cirrhotic patients while GT-4 arms explore treatment with and without ribavirin.

“We are very encouraged by the strong SVR12 rates from this simplified 2-DAA, once-daily regimen that includes our lead HCV protease inhibitor, ABT-450,” commented Jay R. Luly, Ph.D., President and Chief Executive Officer. “We look forward to data from Phase 3 studies of three-DAA regimens containing ABT-450 being reported in the coming months.”

Protease Inhibitor Collaboration with AbbVie (formerly the research-based pharmaceutical business of Abbott Laboratories)

In December 2006, Enanta and Abbott announced a worldwide agreement to collaborate on the discovery, development and commercialization of HCV NS3 and NS3/4A protease inhibitors and HCV protease inhibitor-containing drug combinations. ABT-450 is a protease inhibitor identified as a lead compound through the collaboration. Under the agreement, AbbVie is responsible for all development and commercialization activities for ABT-450. Enanta received $57 million in connection with signing the collaboration agreement, has received $55 million in subsequent clinical milestone payments, and is eligible to receive an additional $195 million in payments for regulatory milestones, as well as double-digit royalties worldwide on any revenue allocable to the collaboration's protease inhibitors. Also, for any additional collaborative HCV protease inhibitor product candidate developed under the agreement, Enanta holds an option to modify the U.S. portion of it rights to receive milestone payments and worldwide royalties. With this option, Enanta can fund 40 percent of U.S. development costs and U.S. commercialization efforts (sales and promotion costs) for the additional protease inhibitor in exchange for 40 percent of any U.S. profits ultimately achieved after regulatory approval instead of receiving payments for U.S. commercial regulatory approval milestones and royalties on U.S. sales of that protease inhibitor.

About Enanta

Enanta Pharmaceuticals is a research and development-focused biotechnology company that uses its robust chemistry-driven approach and drug discovery capabilities to create small molecule drugs in the infectious disease field. Enanta is discovering and developing novel inhibitors designed for use against the hepatitis C virus (HCV). These inhibitors include members of the direct acting antiviral (DAA) inhibitor classes – protease (partnered with AbbVie), NS5A (partnered with Novartis) and nucleotide polymerase – as well as a host-targeted antiviral (HTA) inhibitor class targeted against cyclophilin. Additionally, Enanta has created a new class of antibiotics, called Bicyclolides, for the treatment of multi-drug resistant bacteria, with a focus on developing an intravenous and oral treatment for hospital and community MRSA (methicillin-resistant Staphylococcus aureus) infections.

Forward Looking Statements Disclaimer

This press release contains forward-looking statements, including with respect to clinical data, plans for announcing additional data, and the planned clinical development of ABT-450. Statements that are not historical facts are based on our management's current expectations, estimates, forecasts and projections about our business and the industry in which we operate and our management's beliefs and assumptions. The statements contained in this release are not guarantees of future performance and involve certain risks, uncertainties and assumptions, which are difficult to predict. Therefore, actual outcomes and results may differ materially from what is expressed in such forward-looking statements. Important factors that may affect actual results include final results of ongoing clinical trials, the development and marketing efforts of AbbVie (our collaborator on ABT-450), regulatory actions affecting clinical development of ABT-450 and clinical development of competitive product candidates. Enanta cautions investors not to place undue reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this release, and Enanta undertakes no obligation to update or revise these statements, except as may be required by law.

Source

AASLD-Hepatitis B and C are responsible for 71 percent of liver cancer deaths/58 percent of cirrhosis deaths

Published on Nov 3, 2013 - WebsEdgeHealth          

Theo Heller, MD, Chief, Translational Hepatology Unit, National Institutes of Health, talks to AASLD TV about the exciting new developments in this area of research and new information coming out of the Global Burden of Disease Studies.

Assessing the Global and Regional Burden of Liver Disease

Presented: November 3, 2013

Researchers from Australia presented their research on the underlying causes of liver cancer and cirrhosis deaths at the Annual Meeting of the American Association for the Study of Liver Diseases, concluding that these two diseases result in 1.75 million deaths each year. Viral hepatitis caused two thirds of those deaths. "If you consider deaths from hepatitis B and C together, said Benjamin Cowie, MBBS, PhD, FRACP, "the Global Burden of Death Study (GBD) 2010 estimates around 1.3 million people lost their lives to these infections, which is comparable to the respective burdens of HIV/AIDS, tuberculosis, and malaria."

This is the first study to categorize deaths attributable to viral hepatitis, alcohol, and other causes of cirrhosis and liver cancer separately. "This allows examination of the specific mortality associated with each condition, which clearly has great importance when considering interventions to address the population impact of liver disease in particular countries or regions, as well as globally," said Dr. Cowie.

According to the study, chronic liver disease is a leading cause of human mortality. Hepatitis B and C are responsible for 71 percent of liver cancer deaths and 58 percent of cirrhosis deaths, whereas alcohol is responsible for 25 percent of all deaths caused by liver cancer and cirrhosis. The toll taken by hepatitis B and C differs by region with hepatitis C causing a greater number of deaths in the US and Western Europe, and hepatitis B causing more deaths in China and India.

In addition to recommending a greater priority to be given to viral hepatitis globally, the regional differences in the predominant cause of chronic liver disease -- hepatitis B, hepatitis C, and alcohol abuse -- prompted the study authors to recommend prevention responses to be specific to regional needs.

"I think that there is clear evidence that in many countries, and at the global level, political and public health responses to chronic liver disease have not been commensurate with the burden of disease. This is especially the case for chronic viral hepatitis, said Dr. Cowie. "In Australia, for example, liver cancer is now the fastest increasing cause of cancer death - predominantly driven by chronic viral hepatitis - and less than 5% of people living with chronic viral hepatitis are currently receiving treatment."

"The GBD 2010 data suggest that addressing the global burden of liver disease, particularly chronic viral hepatitis, would be a fundamental step towards addressing a major cause of preventable deaths worldwide," concludes Dr. Cowie.

The 2010 GBD is the most recent version of the study and was funded by the Bill and Melinda Gates Foundation and coordinated by the Institute for Health Metrics and Evaluation (IHME) at the University of Washington. The GBD is a comprehensive regional and global assessment of mortality and disability from major diseases, injuries, and risk factors. The study is a collaborative effort between hundreds of experts worldwide. The study was published and can be found on the IHME website at www.healthmetricsandevaluation.org/gbd.


Abstract title:
The global burden of liver disease attributable to hepatitis B, hepatitis C, and alcohol: increasing mortality, differing causes

###

AASLD is the leading medical organization for advancing the science and practice of hepatology. Founded by physicians in 1950, AASLD's vision is to prevent and cure liver diseases. This year's Liver Meeting®, held in Washington, November 2-5, will bring together more than 9,000 researchers from 55 countries.

A pressroom will be available from November 1 at the annual meeting. For copies of abstracts and press releases, or to arrange researcher interviews, contact Gregory Bologna at 703-299-9766.

Press releases and all abstracts are available online at www.aasld.org.

AASLD-Janssen Will Present New Data For Simeprevir In Genotype 1 Hepatitis C Patients W-compensated Liver Disease

Simeprevir Administered Once Daily as Part of Combination Therapy Demonstrates Sustained Virologic Response in Treatment-Naïve and Treatment-Experienced Genotype 1 Chronic Hepatitis C Adult Patients 

Janssen announced today the presentation of new data for simeprevir in genotype 1 chronic hepatitis C patients with compensated liver disease at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, DC. These data include analyses of simeprevir in the Phase 3 QUEST-1 and QUEST-2 studies in treatment-naïve patients and the Phase 3 PROMISE study in prior relapse patients, including patients with the IL28B TT genotype and METAVIR scores of F4. This follows last week's unanimous vote by the FDA's Antiviral Drugs Advisory Committee to recommend approval of simeprevir.
 
Data from the Phase 2a COSMOS study of simeprevir administered once daily with Gilead's investigational nucleotide inhibitor sofosbuvir, with and without ribavirin, in genotype 1 chronic hepatitis C adult patients with compensated liver disease will also be presented during a late-breaking oral session on Monday, November 4.
 
Simeprevir Administered Once Daily as Part of Combination Therapy Demonstrates Sustained Virologic Response in Treatment-Naïve and Treatment-Experienced Genotype 1 Chronic Hepatitis C Adult Patients
 
WASHINGTON (Nov. 2, 2013) -- Janssen R&D Ireland (Janssen) today announced the presentation of new data at The Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, DC for the investigational protease inhibitor simeprevir (TMC435) in the treatment of genotype 1 chronic hepatitis C in treatment-naïve and treatment-experienced adult patients with compensated liver disease. In analyses of the Phase 3 QUEST-1 and QUEST-2 studies in treatment-naïve patients and the Phase 3 PROMISE study in prior relapse patients, the efficacy of simeprevir was observed in hepatitis C patients, including patients with the IL28BTT genotype and METAVIR scores of F4.
 
"Patients with certain baseline characteristics can be more likely to fail or relapse after prior treatment," said Ira Jacobson, M.D., simeprevir clinical trial investigator, chief of the Division of Gastroenterology and Hepatology, Vincent Astor Distinguished Professor of Medicine, Weill Cornell Medical College, and attending physician, New York-Presbyterian Hospital/Weill Cornell Medical Center. "The breadth of simeprevir data presented at AASLD reinforce its potential as a treatment option for patients and will offer important guidance to physicians once simeprevir is approved."
 
On October 24, the U.S. Antiviral Drugs Advisory Committee of the FDA voted unanimously (19-0) to recommend approval of the new drug application filed by Janssen Research & Development, LLC for simeprevir administered once daily with pegylated interferon and ribavirin for the treatment of genotype 1 chronic hepatitis C virus (HCV) in adult patients with compensated liver disease.
 
Pooled Analysis from QUEST-1 and QUEST-2 Confirms Clinical Benefit of Simeprevir in Sub-Populations of Patients (Abstract 1122)
In a pooled analysis of the Phase 3 QUEST-1 and QUEST-2 studies, 80 percent of treatment-naïve patients treated with simeprevir in combination with pegylated interferon and ribavirin achieved the primary endpoint of sustained virologic response 12 weeks after the end of treatment (SVR12) compared to 50 percent of patients treated with placebo plus pegylated interferon and ribavirin. The pooled analysis found that 61 percent of patients with the IL28B TT genotype, 60 percent of patients with a METAVIR score of F4 and 75 percent of patients with genotype 1a HCV treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 21 percent, 34 percent and 47 percent of patients taking placebo plus pegylated interferon and ribavirin, respectively. Among patients with the genotype 1a Q80K polymorphism at baseline, 58 percent of patients treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 52 percent of patients treated with placebo in combination with pegylated interferon and ribavirin, but the difference was not statistically significant.
 
Eight percent and 10 percent of patients treated with simeprevir combined with pegylated interferon and ribavirin experienced on-treatment failure and relapse, respectively, compared to 33 percent and 15 percent of patients taking placebo plus pegylated interferon and ribavirin, respectively. Three percent of patients treated with simeprevir discontinued treatment early due to an adverse event compared to two percent of patients treated with placebo.
 
Analysis from PROMISE Reinforces Efficacy of Simeprevir in Sub-Populations of Patients (Abstract 1092)
In the pivotal Phase 3 PROMISE study, 79 percent of treatment-experienced hepatitis C patients treated with simeprevir in combination with pegylated interferon and ribavirin who previously experienced a relapse after prior treatment with pegylated interferon-based therapy achieved the primary endpoint of SVR12 compared to 37 percent of patients treated with placebo plus pegylated interferon and ribavirin. In this sub-analysis, 65 percent of patients with the IL28B TT genotype, 74 percent of patients with a METAVIR score of F4 and 70 percent of patients with genotype 1a HCV treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 19 percent, 26 percent and 28 percent of patients taking placebo plus pegylated interferon and ribavirin, respectively.Among patients with the genotype 1a Q80K polymorphism at baseline, 47 percent of patients treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 30 percent of patients treated with placebo in combination with pegylated interferon and ribavirin.
 
The most common adverse events in patients treated with simeprevir combined with pegylated interferon and ribavirin in the first 12 weeks were fatigue, headache and influenza-like illness. Three percent and 18 percent of patients treated with simeprevir combined with pegylated interferon and ribavirin experienced on-treatment failure and relapse, respectively, compared to 27 percent and 34 percent of patients taking placebo plus pegylated interferon and ribavirin, respectively.
 
"We are very proud of the depth and breadth of our clinical trial program," said Gaston Picchio, Disease Area Leader Hepatitis, Janssen Research & Development. "Following last week's positive vote from the FDA's Antiviral Drugs Advisory Committee to recommend approval of simeprevir, we look forward to making simeprevir available to patients living with chronic HCV."
 
About Hepatitis C
Hepatitis C, a blood-borne infectious disease of the liver and a leading cause of chronic liver disease, is the focus of a rapidly evolving treatment landscape. Approximately 150 million people are infected with hepatitis C worldwide - including approximately 3.2 million people in the United States - and 350,000 people per year die from the disease globally. When left untreated, hepatitis C can cause significant damage to the liver including cirrhosis. Additionally, hepatitis C may increase the risk of developing complications from cirrhosis, which may include liver failure.
 
About Simeprevir
Simeprevir (TMC435) is an investigational NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and its affiliated companies and Medivir AB for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease, including all stages of liver fibrosis. Simeprevir works by blocking the viral protease enzyme that enables the hepatitis C virus to replicate in host cells.
 
Janssen is responsible for the global clinical development of simeprevir and has acquired exclusive, worldwide marketing rights, except for the Nordic countries. Medivir AB will retain marketing rights for simeprevir in these Nordic countries under the marketing authorization held by Janssen-Cilag International NV. Simeprevir was approved on September 27, 2013 in Japan for the treatment of genotype 1 hepatitis C and a Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic hepatitis C.
 
Simeprevir is also being studied in several interferon-free regimens using selected combinations of direct-acting antiviral agents with different mechanisms of action. To date, more than 3,700 patients have been treated with simeprevir in clinical trials.
 
In October, Janssen Pharmaceuticals, Inc. acquired the investigational compound GSK2336805, an NS5a replication complex inhibitor in Phase 2 development for the treatment of chronic HCV, from an affiliate of GlaxoSmithKline plc. Since being acquired, the compound has been renamed JNJ-56914845. Janssen Pharmaceuticals plans to initiate Phase 2 studies to evaluate the use of JNJ-56914845 in interferon-free combinations with simeprevir and TMC647055, the company's non-nucleoside polymerase inhibitor, for the treatment of chronic HCV in adult patients with compensated liver disease.
 
For additional information about simeprevir clinical trials, please visit www.clinicaltrials.gov.
 
About Janssen R&D Ireland
 
At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in oncology, immunology, neuroscience, infectious diseases and vaccines, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Janssen R&D Ireland is part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Please visit http://www.janssenrnd.com for more information. #
 
###
Craig Stoltz
Director, Product Communication
Global Pharmaceuticals Communication & Public Affairs
 
Janssen Global Services, LLC
Phone 609-730-2823
Fax 609-730-3770
Mobile 215-779-9396
cstoltz@its.jnj.com

Bristol seeks Japan approval of all-oral hepatitis C treatment

Bristol seeks Japan approval of all-oral hepatitis C treatment
By Bill Berkrot

(Reuters) - Bristol-Myers Squibb Co has filed with Japanese health regulators seeking approval of its experimental all-oral combination of hepatitis C treatments, the U.S. drugmaker said on Saturday.

The submission with Japan's Pharmaceutical and Medical Devices Agency marks the first time that any drugmaker has filed for approval of a hepatitis C treatment regimen that does not include either of the standard older treatments - the injected, difficult-to-tolerate interferon, or ribavirin, a pill.

Gilead Sciences Inc, widely seen as the leader in a crowded race to develop highly effective, interferon-free treatments for the serious liver disease, has sought U.S. approval of its highly regarded anti-viral drug sofosbuvir in combination with ribavirin. A Food and Drug Administration advisory panel last week voted unanimously to recommend its approval.

The Bristol-Myers filing was based on data from a Phase III study of Japanese patients who either could not tolerate interferon, which causes miserable flu-like symptoms, or those who had previously failed to be helped by treatment with the older drugs - a particularly tough-to-treat patient population.

Patients in the trial were given a combination of daclatasvir, from a promising new class of drugs called NS5A inhibitors, and the protease inhibitor asunaprevir for 24 weeks. Those who had no detectable levels of the virus in their blood 24 weeks after completing the therapy were deemed to be cured, a measure known as SVR24, for sustained virologic response.

The overall cure rate in the 222-patient study was 84.7 percent, according to the data to be presented next week at the American Association for the Study of Liver Diseases (AASLD) meeting in Washington.

Of those who were either ineligible for or intolerant of treatment with interferon, the cure rate was 87.4 percent, while 80.5 percent of past nonresponders to the older drugs were deemed cured.

"The Phase III study results of daclatasvir plus asunaprevir are exciting to see, especially in this difficult-to-treat patient population," Kazuaki Chayama, the study's lead investigator from Hiroshima University, said in a statement.

Twenty-eight patients dropped out of the study - a 12.6 percent discontinuation rate - and about 6 percent, or 13 patients, reported serious side effects, primarily elevated liver enzymes, an indication of inflammation.

JAPAN FOCUS

Bristol-Myers has made Japan a particular focus of its all-oral efforts at tackling the hepatitis C virus, which if left untreated can cause cirrhosis, liver cancer or the need for a transplant.

About 1.2 million people in Japan suffer from hepatitis C. The patients tend to be older than those in other developed countries and about 70 percent have Genotype 1b, a form of the virus with very low response rates to the older treatments.

Several other companies are also developing all-oral hepatitis C treatments, including AbbVie Inc, Merck & Co and Johnson & Johnson, and expect to be able to shorten treatment duration to 12 weeks from the current 24- or 48-week regimens.

Bristol early next year plans to begin Phase III testing of an all-oral, three-drug combination that adds BMS791325 - a non-nucleoside polymerase inhibitor - to the two drugs tested in the Japanese study. The company envisions that its three-drug therapy will involve one combination pill taken twice a day for a 12-week course of treatment.

About 170 million people worldwide are infected with the hepatitis C virus. Some analysts believe the market for all-oral hepatitis C treatments could reach $20 billion as many more people get tested for the virus, given new testing recommendations, very high cure rates, shorter treatment durations and tolerable side effects seen with the newer drugs in clinical trials.

It is believed that tens of thousands of hepatitis C patients have delayed treatment while awaiting the new drugs expected to start reaching the market next year in order to avoid the unpleasant side effects of interferon. Physicians would also like to see regimens that do not require ribavirin, which can cause anemia, rash and other side effects.

(Editing by Matthew Lewis)
http://health.yahoo.net/news/s/nm/bristol-seeks-japan-approval-of-all-oral-hepatitis-c-treatment

AASLD-Phase III data show Boehringer Ingelheim's faldaprevir* was highly effective in a broad range of patients with genotype-1 hepatitis C

02 November 2013
Phase III data show Boehringer Ingelheim's faldaprevir* was highly effective in a broad range of patients with genotype-1 hepatitis C

• Pivotal Phase III STARTVerso™ data show efficacy of faldaprevir* in difficult-to-cure patient populations such as those with HIV co-infection and advanced liver disease
• 84% of patients benefited from a shorter time on treatment and the majority went on to achieve viral cure, with no compromise on safety and tolerability (STARTVerso™1&2)¹
• Second-generation protease inhibitor faldaprevir* is being investigated in combinations both with and without interferon

For media outside of the U.S.A., UK and Canada only

INGELHEIM, 2 November, 2013 – Boehringer Ingelheim today announced new data from its Phase III clinical trial programme, STARTVerso™, which evaluates faldaprevir* in combination with pegylated interferon and ribavirin (PegIFN/RBV). Patients with genotype-1 (GT-1) hepatitis C (HCV) who have not received previous treatment (treatment-naïve: STARTVerso™1&2),¹ treatment-experienced patients (STARTVerso™3),² and HIV co-infected patients (STARTVerso™4)³ participated in this study programme. The results from these and additional studies will be presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), also known as The Liver Meeting®, taking place 1-5 November in Washington, D.C.

In STARTVerso™1&2, 84% of treatment-naïve patients receiving faldaprevir* were able to shorten the total time on treatment from 48 to 24 weeks; 83% of these patients achieved viral cure (SVR12).¹ Overall, 73% and 72% of patients achieved SVR12 with faldaprevir* 120mg and 240mg regimens, respectively. Interim results from STARTVerso™4 showed that 74% of patients with HCV/HIV co-infection treated with faldaprevir* had undetectable HCV 4 weeks after the conclusion of treatment (SVR4), a response rate similar to that seen with HCV mono-infection.³ Additionally, treatment of difficult-to-cure patients who have relapsed on previous HCV treatment (STARTVerso™3) demonstrated viral cure rates of 70% with faldaprevir*.² In the same study, patients who partially responded and those who showed no response to previous treatment achieved viral cure rates of up to 58% and 33%, respectively.³ For the full STARTVerso™ results, see notes to editors.

"These data are encouraging and reinforce the potential benefits of faldaprevir* as an effective treatment for genotype-1 infected HCV patients," said Ira Jacobson, M.D., Chief of the Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York. "The broad populations studied in STARTVerso™ and the fact that very few patients discontinued treatment due to adverse events provides physicians with confidence in faldaprevir* as an important potential addition to the available agents for the treatment of hepatitis C."

More than 2,200 patients have been studied in the STARTVerso™ trial programme, including patients with difficult-to-cure types of HCV:

• Over 300 patients in the programme have HCV/HIV co-infection;3 these patients have higher levels of HCV in their blood and can be more difficult to cure⁴
• 677 patients were treatment-experienced, meaning they had attempted previous HCV treatment but did not achieve viral cure²
• 40% of patients in STARTVerso™3 had advanced liver disease (≥F3 fibrosis)²
• 59% of patients in STARTVerso™1&2 had a non-CC IL28B genotype;¹ in previous studies, these patients were less likely to achieve viral cure⁵

"The STARTVerso™ trial results are particularly promising given the inclusion of a broad range of patients and the similar success rates seen in both HCV mono and HCV/HIV co-infected patients. These data will form the basis of regulatory submissions and we look forward to the outcome," said Professor Klaus Dugi, Senior Vice President Medicine at Boehringer Ingelheim. “Faldaprevir* may offer a simple and convenient option for patients, due to once-daily dosing and no food restrictions. Faldaprevir* is the foundation of our HCV pipeline and we look forward to presenting pivotal Phase III HCVerso® data for the treatment of HCV as part of an interferon-free regimen in 2014."
Faldaprevir* as part of this interferon-based regimen is likely to offer advantages over first generation protease inhibitors with fewer skin reactions, gastrointestinal events and no additional anaemia. In the STARTVerso™ clinical trial programme, adverse events (AEs) were generally mild and well manageable. Most common AEs included jaundice due to transient bilirubin elevation (unconjugated hyperbilirubinemia), nausea, fatigue, diarrhoea, headache, anaemia and rash. 95% of patients completed faldaprevir* treatment.^1,2,3 For full STARTVerso™ results, see notes to editors.

ADDITIONAL BOEHRINGER INGELHEIM DATA AT THE MEETING

Faldaprevir* in further clinical settings
Further studies adding to the robust portfolio of evidence for faldaprevir* will be presented at the meeting. These include studies exploring drug-drug interactions in patients who are taking oral birth control pills and common medication to treat drug dependence and studies evaluating faldaprevir* in patients who have renal impairment.

Faldaprevir* as part of an interferon-free regimen
Additional news from Boehringer Ingelheim was released today featuring data from the collaborative trial with Presidio Pharmaceuticals. The ongoing Phase II trial investigating the regimen of faldaprevir*, deleobuvir* and PPI-668 (with and without ribavirin) in genotype-1a infected patients was accepted as late breaker and will be presented on Monday.

NOTES TO EDITORS
Phase III STARTVerso™ results
STARTVerso™1&2

Treatment-naïve patients were randomised 1:2:2 to receive 48 weeks of PegIFN/RBV plus: placebo (Arm 1); faldaprevir* 120mg once-daily for 12 or 24 weeks (Arm 2); or faldaprevir* 240mg once-daily for 12 weeks (Arm 3). SVR12 rates were:¹

• Arm 1: 50% (131/264) 
• Arm 2: 73% (382/521) 
• Arm 3: 72% (378/524)

Patients in arms 2 and 3 stopped all treatment at week 24 if HCV RNA <25IU/mL was detected or undetected at week 4 and undetected at week 8 of treatment. Results were:¹

• Arm 2: 84% (436/521) of which 83% (362/436) achieved SVR12
• Arm 3: 84% (441/524) of which 83% (368/441) achieved SVR12

In the study, the most common AEs were gastrointestinal events and anaemia, occurring in 11%/18% and 14%/13% of patients treated with 120mg/240mg faldaprevir* regimens respectively. Hyperbilirubinemia occurred in 12% and 46% of patients, respectively.¹

STARTVerso™3

The trial included 3 cohorts of treatment-experienced patients who had: prior relapse (cohort 1), prior partial response (cohort 2) and prior null response (cohort 3).²

Cohort 1
Patients were randomised 1:2:2 to receive 48 weeks of PegIFN/RBV plus: placebo (placebo); faldaprevir* 240mg once-daily for 12 weeks (FDV12W); or faldaprevir* 240mg once-daily for 24 weeks (FDV24W). SVR12 rates were:²

• Placebo: 14% (7/49)
• FDV12W: 70% (69/99)
• FDV24W: 70% (71/102)
• 87% of patients stopped all treatment at week 24 of whom 75% achieved SVR12

Cohort 2
Patients were randomised 1:2:2 to receive 48 weeks of PegIFN/RBV plus: placebo (placebo); faldaprevir* 240mg once-daily for 12 weeks (FDV12W); or faldaprevir* 240mg once-daily for 24 weeks (FDV24W). SVR12 rates were:²

• Placebo: 3% (1/29)
• FDV12W: 58% (33/57)
• FDV24W: 47% (26/55)

Cohort 3
Patients were randomised 1:1 to receive faldaprevir* 240mg once-daily for 12 weeks (FDV12W) or faldaprevir* 240mg once-daily for 24 weeks (FDV24W) with PegIFN/RBV for 48 weeks. SVR12 rates were:²

• FDV12W: 33% (48/145)
• FDV24W: 33% (46/141)

AEs of at least moderate intensity included gastrointestinal side effects, which occurred in 20% and 17% of patients in the 12- and 24-week faldaprevir* arms respectively. Also, anemia occurred in 10% of patients in both faldaprevir* arms.²

STARTVerso™4

The ongoing trial includes patients co-infected with HCV and HIV who are HCV treatment-naïve or have relapsed after previous HCV therapy. Patients received 48 weeks of PegIFN/RBV plus either: faldaprevir* 120mg once-daily for 24 weeks (Arm A); or faldaprevir* 240mg once-daily for 12 or 24 weeks (dependent on randomisation at week 12) (Arm B). SVR4 rates were:³

• Arm A: 72% (89/123)
• Arm B, faldaprevir* 12 weeks: 79% (66/84)
• Arm B, faldaprevir* 24 weeks: 84% (72/86)
• Arm B, total: 76% (140/185^a)
• Total: 74% (229/308)

^aincludes additional patients from 240mg treatment group who discontinued prior to week 12
Patients in whom HCV RNA <25IU/mL was detected or undetected at week 4 and undetected at week 8, were randomised 1:1 to stop treatment at week 24 or continue PegIFN/RBV to 48 weeks. Results were:³

• Arm A: 77% (95/123) of which 89% (85/95) achieved SVR4
• Arm B, total: 81% (150/185) of which 87% (131/150) achieved SVR4
• Total: 80% (245/308) of which 88% (216/245) achieved SVR4

The most common AEs in the study were nausea, fatigue and diarrhoea , occurring in 28% and 44%; 32% and 35%; and 25% and 28% with the 120mg and 240mg faldaprevir* regimens respectively.³

 

http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2013/02_novermber_2013_hepatitisc.html

AASLD-Boehringer Ingelheim's interferon-free hepatitis C treatment portfolio strengthened by promising Phase II data

02 November 2013

Boehringer Ingelheim's interferon-free hepatitis C treatment portfolio strengthened by promising Phase II data

• High rate of virologic response in Phase II hepatitis C trial of a 12 week all-oral combination of Boehringer Ingelheim’s faldaprevir* and deleobuvir* and Presidio’s PPI-668* with and without ribavirin¹
• All patients (17/17) who have completed treatment achieved undetectable levels of hepatitis C virus at the end of treatment¹
• 13 of these patients have reached their 4-week post-treatment follow-up and all have undetectable hepatitis C virus (SVR4)¹

 

For media outside of the U.S.A., UK and Canada only
 

INGELHEIM, 2 November, 2013 – Interim data presented today show that all patients (13/13) who reached their 4-week post-treatment follow-up have undetectable levels of hepatitis C virus (SVR4) after completing a 12-week regimen of faldaprevir*, deleobuvir*, PPI-668* and ribavirin.¹ These data from Boehringer Ingelheim’s ongoing Phase II collaborative trial with Presidio Pharmaceuticals will be presented on Monday during the ‘Late-Breaking Posters’ session at the 64^th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), taking place in Washington, D.C. Additional data from the trial show 100% of patients (12/12) treated with a ribavirin-free regimen had hepatitis C virus (HCV) levels below the lower level of quantification at 4 weeks.¹ Safety and tolerability appears to be better in this ribavirin-free treatment arm compared to those with ribavirin.¹

“These interim results add to the growing body of evidence for faldaprevir* as an effective treatment for a broad range of genotype-1 infected hepatitis C patients, including the more difficult-to-cure. The trial is still in the early stages but the initial results look promising,” said Professor Klaus Dugi, Senior Vice President of Medicine at Boehringer Ingelheim. “These data further demonstrate the future potential of faldaprevir* as the foundation of interferon-free treatment regimens. Our pivotal HCVerso^® studies which investigate the interferon-free regimen of faldaprevir*, deleobuvir* and ribavirin are currently in Phase III development. We look forward to the final results from both trials in Q2 next year.”

The ongoing Phase II trial features the 12-week regimen both with and without ribavirin in 36 genotype-1a infected patients, one of the more difficult-to-cure types of hepatitis C virus. In addition, more than half the patients in the study (20/36) had pre-existing HCV mutations. This includes the Q80K variant which is common in genotype-1a infected patients² and has been associated with reduced responses to some HCV protease inhibitors. Notably, all 12 patients in the study with pre-existing Q80K mutations are responding well to treatment with the faldaprevir*-based interferon-free regimen.¹

To date, all patients in the study have received at least 4 weeks of treatment and 97% (35/36) achieved HCV levels below the lower limit of quantification at week 4. One patient had an initial virologic response but then exhibited viral breakthrough and was discontinued after 5 weeks of treatment. Overall, adverse events in the study have been mild to moderate, with the incidence and severity of skin rashes and gastrointestinal side effects similar to those observed in previous trials studying faldaprevir* and deleobuvir*. For further results see notes to editors.

Overview of Boehringer Ingelheim’s HCV trial programme
 

Boehringer Ingelheim’s hepatitis C clinical trial programme includes a broad range of genotype-1 infected patients. The programme features three treatment regimens, with faldaprevir* as the foundation:
 

Study	Regimes	Population	Status
STARTVerso™	Faldaprevir* pegylated interferon, ribavirin	GT-1 , TN, TE, HCV/HIV co-infection, advanced liver disease	Regulatory submissions pending
For results see the STARTVerso press release here
HCVerso®	Faldaprevir*, deleobuvir*, ribavirin	GT-1b, TN, TE, advanced liver disease	Phase III results expected Q2 2014
Presidio collaboration	Faldaprevir*, deleobuvir*, PPI-668* +/- ribavirin	GT-1a, TN, non-cc IL28B	Phase II final results expected Q2 2014

 

An individualised approach to hepatitis C

The breadth of patients studied in Boehringer Ingelheim’s hepatitis C trial programme reflects a population that physicians see in the clinic, including those with difficult types of hepatitis C virus to cure.

“The huge diversity between hepatitis C patients, due to differing personal factors and variations in the virus, highlight the importance of an individualised approach to treatment,” said Graham Foster, Professor of Hepatology, Queen Mary’s, London. “The difference between HCV genotypes is substantial. For example, genotype-1a and 1b share only around 70% of the same genetic material which is more distant than the genetic similarity between humans and some other animals and patients have differing degrees of liver damage that may require changes to the therapeutic approach. Given the diversity of the disease and the virus it is likely that each patient will need to be assessed on an individual basis and the best treatment assigned accordingly.”

For more information on the importance of an individualised approach to hepatitis C, view the video here
 

NOTES TO EDITORS
Phase IIa Presidio collaboration trial results The trial includes 36 treatment-naïve patients with genotype-1a HCV treated for 12 weeks with an all-oral regimen, with 24 weeks of post-treatment follow-up. The primary endpoint is viral cure 12 weeks after treatment completion (SVR12). There are three cohorts in this study:¹

• Cohort 1: faldaprevir* 120 mg once-daily (QD), PPI-668 200mg QD and deleobuvir* 600mg twice-daily (BID) with ribavirin (n=12) 
• Cohort 2: faldaprevir* 120 mg QD, PPI-668 200mg QD and deleobuvir* 400mg BID with ribavirin (n=12) 
• Cohort 3: faldaprevir* 120mg QD, PPI-668 200mg QD and deleobuvir* 600 mg BID, without ribavirin (n=12)

Thirty-six patients in this study have reached week 4 of treatment, 17 patients have reached the end of treatment (12 weeks) and 13 patients have reached their 4 week post-treatment follow-up. Interim results show:¹

• 97% of patients (35/36) achieved HCV levels below the lower limit of quantification at week 4
• 100% of patients (17/17) that completed the full course of treatment had undetectable hepatitis C virus at the conclusion of treatment
• 100% of patients (13/13) that completed the full course of treatment achieved SVR4

To date there has been just one treatment failure due to viral breakthrough. One patient had an initial virologic response but then exhibited viral breakthrough and was discontinued after 5 weeks of treatment. Only one AE was rated as ‘severe’ and attributable to study drugs; one patient reported severe fatigue in week 11 and the event was resolved with no change in treatment.¹

AASLD-High cure rates seen with Merck oral hepatitis drugs -study

High cure rates seen with Merck oral hepatitis drugs -study

By Bill Berkrot

Sat Nov 2, 2013 1:30pm GMT

Nov 2 (Reuters) - A combination of two oral hepatitis C treatments developed by Merck & Co led to high cure rates in previously untreated patients, indicating the company is a contender in the race to find new treatments for the liver destroying virus.

The treatments tested with and without the older drug ribavirin led to cure rates of 96 percent to 100 percent, according to interim data from a small midstage clinical trial.

The results appear to confirm Merck will be competitive in the crowded race to develop interferon-free treatments for hepatitis C, assuming they are repeated in larger studies that include more difficult to treat patient populations, such as those not helped by prior therapy.

The 65-patient, 3-arm study tested MK-5172, a protease inhibitor, combined with MK-8742 from a highly promising new class of drugs called NS5A inhibitors for 12 weeks of treatment.

Based on data available at the time the interim results were released, 55 of 56 patients who completed the therapy were considered to be cured of the virus which is transmitted through infected blood from sources such as infected hypodermic needles or blood transfusions.

Patients who have no detectable levels of the virus in their blood 12 weeks after completing 12 weeks of treatment were deemed to be cured - a measure known as SVR 12, for sustained virologic response.

In the arm of the study that did not include the older oral medicine ribavirin, all 11 patients who completed therapy with MK-5172 and the higher 50 milligram dose of MK-8742 taken once a day achieved SVR 12.

All 12 patients who began that arm of the study had Genotype 1b of the liver disease, which is prevalent in Europe and Japan. It is considered somewhat easier to treat than Genotype 1a, the most common form of the virus seen in the United States, which may require a third drug in the regimen to achieve similarly high cure rates.

The other two arms - one testing 50 mg of MK-8742 and one using 20 mg - did include ribavirin given twice a day.

With the lower dose of the NS5A inhibitor, all 21 patients who completed therapy were deemed cured. In the group that received the higher dose in the three-drug combination, 23 of 24, or 96 percent, reached SVR 12. About three quarters of the patients in those arms were Genotype 1a.

Of the 65 patients in the study, only one had experienced a relapse of the virus, according to the data to be presented on Sunday at the American Association for the Study of Liver Diseases (AASLD) meeting in Washington.

"We are encouraged by these preliminary data for the combination of MK-5172 and MK-8742. It's a one-two punch with both arms equally strong," said Eliav Barr, head of infectious diseases for Merck.

SHORTER TREATMENT DURATION

Current standard treatment regimens for hepatitis C take 24 or 48 weeks and includes injected interferon, which causes miserable flu-like symptoms that lead many patients to avoid or discontinue treatment.

Several companies are developing new all-oral combinations that in clinical trials have cut treatment duration to 12 weeks for many patients while significantly increasing cure rates from about 75 percent with current drugs.

Ultimately, physicians would like to also see regimens that do not require ribavirin, which has its own side effect issues, including anemia and rash.

It is believed that tens of thousands of hepatitis C patients have delayed treatment while awaiting the new drugs expected to start reaching the market next year.

Gilead Sciences is widely seen as being in the lead with a safe and effective all-oral combination, with Bristol-Myers-Squibb and AbbVie close behind.

Gilead last week won an approval recommendation from a U.S. Food and Drug Administration advisory panel for its highly regarded sofosbuvir.

Some analysts believe the market for all-oral hepatitis C treatments could reach $20 billion as many more people get tested for the virus, given the very high cure rates, shorter treatment durations and tolerable side effects.

An estimated 170 million people worldwide are infected with hepatitis C, which if left untreated can lead to cirrhosis, need for a transplant or liver cancer.

The Merck drugs were well tolerated with no serious adverse side effects reported. The most common side effects were fatigue, headache and nausea.

Merck plans to expand the Phase II trial to about 400 additional patients, testing its drugs with and without ribavirin, and including those also infected with the HIV virus, those with cirrhosis and patients who have failed to be cured by prior treatments. It is also looking at a regimen of only 8 weeks in previously untreated patients that would include ribavirin.
(Reuters)

Merck Announces Presentation of Interim Data from Study of Investigational Combination of HCV Therapies MK-5172 and MK-8742 at the 2013 American Association for the Study of Liver Diseases (AASLD) Annual Meeting
          

Sustained virologic response at post-treatment follow-up week 12 (SVR 12) seen in 100 percent of patients to date in two of the three combination arms studied

 

WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced the presentation of interim data from the ongoing C-WORTHY Study, a Phase II clinical trial evaluating the efficacy and safety of an all-oral regimen combining once-daily MK-5172, an investigational hepatitis C virus (HCV) NS3/4A protease inhibitor, and MK-8742, an investigational HCV NS5A replication complex inhibitor, with or without twice-daily ribavirin, administered for 12 weeks to treatment-naïve, non-cirrhotic patients with HCV genotype 1a and 1b infection. The interim data show that the administration of MK-5172 and MK-8742 in combination is associated with a sustained virologic response (lack of detectable and quantifiable HCV) 12 weeks following the end of study therapy (SVR12). Merck previously announced that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to MK-5172/MK-8742 for treatment of chronic HCV infection.    
 

“We are encouraged by these preliminary data for the combination of MK-5172 and MK-8742,” said, Dr. Eliav Barr, vice president, Infectious Diseases, Merck Research Laboratories. “These data provide further support that we can advance these candidates, which are currently in Phase IIB clinical development, into a broader evaluation in a diverse range of HCV patients.”

C-WORTHY Study
In the C-WORTHY Study, 65 patients (45% male, 11% African American, and 58% genotype 1a infection) were enrolled in one of three 12-week treatment arms (see TABLE). The ribavirin (RBV) arms were stratified by genotype 1a versus genotype 1b. The RBV-free arm included only genotype 1b-infected patients. Virologic response was assessed each week during treatment and at 2, 4, 8, 12 and 24 weeks after the end of treatment. The primary efficacy endpoint of the trial was the proportion of patients who achieved sustained virologic response at post-treatment follow-up week 12 (SVR12).
The primary analysis population was per protocol, including patients who did not have protocol violations and had received the correct study medications. A total of 58/65 enrolled patients met these criteria (see TABLE).
   
Of the seven patients who were not in the per-protocol population, four achieved SVR12 and three discontinued early for reasons other than adverse experiences or virologic failure.
Among the entire study population of 65 patients, one patient (1.5%) experienced a relapse with detectable HCV RNA at follow-up week 4 and 12.
   
TABLE
Primary Analysis Population: Per Protocol*

Arm	Regimen	N	GT1a / GT1b	SVR4	SVR12#
1	MK-5172 (100 mg) + MK-8742 (20 mg) + ribavirin	22	76% / 24%	22/22 (100%)	21/21 (100%)
2	MK-5172 (100 mg) + MK-8742 (50 mg) + ribavirin	24	70% / 30%	23/24 (96%)	23/24 (96%)
3	MK-5172 (100 mg) + MK-8742 (50 mg)	12	0% / 100%	12/12 (100%)	11/11 (100%)
* Seven Patients were excluded from the Per Protocol Population   4 patients received incorrect RBV doses (3 received <50% of the prescribed dose:1 given RBV in the RBV-free arm); all achieved HCV-RNA <25 IU/mL at FU12 3 patients discontinued early:1 patient at Day 3 (violated protocol inclusion criterion), and 2 patients at Day 22 and Day 35 (withdrew consent – patients had undetectable HCV RNA at the time of discontinuation) #Two patients have not reached SVR12

      The most frequently reported adverse events occurring in the study were fatigue (26%), headache (22%), nausea (18%), diarrhea (12%), dizziness (11%) and rash (11%). The incidence of anemia (<10 mg/dL hemoglobin) and elevated total bilirubin levels to 2 times the upper limit of normal was 19 percent and 4 percent, respectively, in the RBV-containing arms (combined arms 1 and 2), and 0 percent and 0 percent, respectively, in the RBV-free arm. No grade 3 or 4 laboratory abnormalities were observed. There were eight cases of rash. Seven cases of rash were observed in the RBV-containing arms; half of these cases were attributed to RBV. The single case in the RBV-free arm was not study drug related and was mild in intensity. No early discontinuations due to drug-related adverse events were recorded.
   
The C-WORTHY trial has been expanded to evaluate the safety and efficacy of MK-5172 and MK-8742, with or without RBV, in difficult-to-cure HCV genotype 1-infected patient populations. Approximately 400 additional HCV genotype 1-infected patients have been enrolled in this trial. The expanded C-WORTHY study is testing:
   

• 8 week regimen of MK-5172/MK-8742 + RBV in treatment naïve non-cirrhotic patients
• 12 week regimen of MK-5172/MK-8742 without RBV in treatment-naïve non-cirrhotic patients
• 12 week regimens (MK-5172/MK-8742 with or without RBV) among HIV co-infected patients
• 12 or 18 week regimens (MK-5172/MK-8742 with or without RBV) in patients with cirrhosis
• 12 or 18 week regimens (MK-5172/MK-8742 with or without RBV) in patients who had failed to respond to prior peginterferon and RBV therapy (“null responders”).

Details on the C-WORTHY Study, as well as additional phase II trials for MK-5172 and MK-8742, can be viewed on ClinicalTrials.gov.

About Merck
Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside of the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.
   
Merck Forward-Looking Statement
This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
   
Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Merck’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Merck’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
   
Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2012 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

AASLD-Gilead Announces New Sustained Viral Response Data for Sofosbuvir-Based Regimens in Genotype 3-Infected Hepatitis C Patients

Gilead Announces New Sustained Viral Response Data for Sofosbuvir-Based Regimens in Genotype 3-Infected Hepatitis C Patients

-- Results from Phase 3 VALENCE Study Confirm Efficacy and Safety of All-Oral Sofosbuvir-Based Regimen in Hepatitis C Patients with Genotype 3 Infection --

WASHINGTON--(BUSINESS WIRE)--Nov. 2, 2013-- Gilead Sciences, Inc. (Nasdaq:GILD) today announced results from two studies, the Phase 3 VALENCE study and the Phase 2 LONESTAR-2 study, evaluating the investigational once-daily nucleotide analogue sofosbuvir for the treatment of chronic hepatitis C virus (HCV) infection among patients infected with genotype 3 HCV. These data will be presented this week at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2013) taking place in Washington, D.C.

In the Phase 3 VALENCE study, 85 percent (n=212/250) of treatment-naïve or treatment-experienced patients with genotype 3 HCV who received a 24-week regimen of sofosbuvir plus ribavirin (RBV) achieved a sustained virologic response 12 weeks after treatment (SVR12). Patients who achieve SVR12 are considered cured of HCV infection.

"The VALENCE results demonstrate the high efficacy of a 24-week, sofosbuvir-based, interferon-free treatment regimen for genotype 3 HCV patients with and without liver cirrhosis," said Stefan Zeuzem, MD, Professor of Medicine and Chief of the Department of Medicine, Goethe University Hospital, Frankfurt, Germany, and principal investigator for the VALENCE study. "Notably, the majority of these patients had failed prior therapy, and sofosbuvir was able to produce a sustained virologic response."

Additionally, the Phase 2 LONESTAR-2 study evaluated 12 weeks of sofosbuvir, RBV and pegylated interferon (peg-IFN) among patients who had previously failed treatment with peg-IFN/RBV, approximately half of whom had cirrhosis. In this study, 83 percent (n=20/24) of genotype 3 patients achieved SVR12.

There were few discontinuations due to adverse events in VALENCE and LONESTAR-2. Sofosbuvir was well tolerated in VALENCE and adverse events in LONESTAR-2 were consistent with the safety profile of peg-IFN/RBV.

About VALENCE

VALENCE is an ongoing placebo-controlled Phase 3 study in which patients with genotype 2 and 3 HCV infection were originally randomized (4:1) to receive sofosbuvir 400 mg once-daily plus weight-based RBV twice-daily (1,000 or 1,200 mg/day) for 12 weeks (n=334) or placebo (n=85). The study was subsequently amended to extend the treatment duration for genotype 3 patients (n=250) to 24 weeks. Patients randomized to receive placebo were offered treatment in an alternative protocol. Fifty-eight percent of trial participants were treatment-experienced and 21 percent had cirrhosis.

Among genotype 2 HCV patients receiving a 12-week all-oral course of sofosbuvir plus RBV, 93 percent (n=68/73) achieved SVR12.

Two patients receiving sofosbuvir and one patient receiving placebo discontinued treatment due to adverse events. The most common adverse events occurring in =10 percent of patients receiving sofosbuvir were headache, fatigue, pruritus, asthenia and nausea.

About LONESTAR-2

LONESTAR-2 is an ongoing open-label Phase 2 study evaluating the efficacy and safety of a 12-week regimen of sofosbuvir 400 mg once-daily, weight-based RBV twice-daily (1,000 or 1,200 mg/day) and peg-IFN (180 µg/week) among 47 patients with genotype 2 or 3 HCV infection. All patients in the study had previously failed treatment with peg-IFN/RBV and 55 percent had cirrhosis.

Ninety-six percent (n=22/23) of genotype 2 HCV patients achieved SVR12 in the study.

Two patients receiving sofosbuvir discontinued treatment due to adverse events. The most common adverse events occurring in =15 percent of the patients were consistent with the safety profiles of peg-IFN and RBV and included flu-like symptoms, fatigue and anemia.

Further information about these studies can also be found at www.clinicaltrials.gov.

Sofosbuvir is an investigational product and its safety and efficacy have not been established.

About Gilead Sciences

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

Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including risks related to the possibility of unfavorable results from ongoing and subsequent clinical trials involving sofosbuvir, including in combination with other products, for the treatment of HCV, and the possibility that regulatory authorities may not approve sofosbuvir for HCV-related indications and any marketing approval may have substantial limitations on its use. As a result, sofosbuvir may never be successfully commercialized. In addition, Gilead may make a strategic decision to discontinue development of sofosbuvir if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. 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 Quarterly Report on Form 10-Q for the quarter ended September 30, 2013, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

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



Source: Gilead Sciences, Inc.

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