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

November 02, 2013 09:00 AM Eastern Daylight Time 

INGELHEIM, Germany--(EON: Enhanced Online News)--For media outside of the U.S.A., UK and Canada only

“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”

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 inhibitors³. 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		Regimen			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

*Faldaprevir, deleobuvir and PPI668 are investigational compounds and not yet approved. Their safety and efficacy have not yet been fully established.

# # #

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

NewsHome

The Boehringer Ingelheim NewsHome: An innovative resource for journalists

The Boehringer Ingelheim hepatitis C www.newshome.com is the one-stop-shop for clear, concise and easy to understand information about hepatitis C for the media.

About STARTVerso™ and HCVerso^®

For information on the interferon-free Phase III HCVerso® trials please refer to the Clinical Trials backgrounder, available on NewsHome.

For the full ‘Notes to Editors’ and ‘References’ please visit:

https://www.boehringer-ingelheim.com/news/news_releases/press_releases/2013/02_novermber_2013_hepatitisc1.html

Contacts

Contact:
Boehringer Ingelheim
Corporate Communications
Media + PR
Reinhard Malin
Tel: +49 (6132) 77-90815
Fax: +49 (6132) 77-6601
Email: press@boehringer-ingelheim.com

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Gilead Announces Phase 2 Results for Sofosbuvir-Based Regimens in Hepatitis C Patients Before and After Liver Transplantation

~ Studies Support Efficacy and Safety of an All-Oral Sofosbuvir-Based Regimen for the Prevention and Treatment of Recurrent HCV Infection Following Liver Transplants ~

WASHINGTON--(BUSINESS WIRE)--Nov. 2, 2013-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from two Phase 2 studies evaluating an all-oral treatment regimen of the investigational once-daily nucleotide analogue sofosbuvir plus ribavirin (RBV) for both the prevention and treatment of recurrent chronic hepatitis C virus (HCV) infection among patients who undergo liver transplantation. The findings will be presented this week at the 64^th Annual Meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2013) in Washington, D.C.

HCV infection is the most common cause of liver transplantation in the United States and Europe. Recurrence of HCV infection is universal among patients with active disease at the time of transplantation and up to 50 percent develop cirrhosis of the liver within five years. Suppression of HCV RNA prior to liver transplantation should reduce the risk of re-infection and its serious complications, but currently available treatment options are often ineffective and poorly tolerated. Similarly, in the post-transplant setting, treatment is generally poorly tolerated and complicated by strong drug interactions with immunosuppressive agents used to prevent the body’s rejection of the transplanted liver.

In a study conducted among pre-transplant HCV patients (Study 2025), up to 48 weeks of sofosbuvir/RBV therapy was administered. Among patients with undetectable HCV (<25 IU/mL) at the time of transplantation, 64 percent (n=25/39) achieved undetectable HCV RNA 12 weeks post-transplant (pTVR12). Patients who achieve pTVR12 are considered cured of HCV infection. In a second study conducted among post-transplant HCV patients (Study 0126), patients with established recurrent HCV infection following liver transplantation received 24 weeks of sofosbuvir/RBV therapy. Seventy-seven percent (n=27/35) of patients in this study have achieved a sustained virologic response four weeks post-treatment (SVR4).

“Recurrence of HCV following liver transplantation almost always occurs in clinical practice. These patients are at higher risk for disease progression, the development of cirrhosis, liver graft failure, re-transplantation and increased morbidity and mortality,” said Michael P. Curry, MD, Medical Director, Liver Transplantation at Beth Israel Deaconess Medical Center, Boston, and an investigator for the pre- and post-liver transplant trials. “In these studies, sofosbuvir clearly demonstrated the potential to improve patient outcomes by either preventing or effectively treating recurrent HCV infection following liver transplantation.”

Three percent and five percent of patients discontinued treatment due to adverse events in the pre- and post-transplant studies, respectively. No serious adverse events reported were associated with sofosbuvir. The most common adverse events observed were consistent with the safety profile of RBV, and included fatigue, anemia, headache and nausea in the pre-transplant study, and fatigue, headache, arthralgia (joint pain) and diarrhea in the post-transplant study.

About the Pre-Transplant Study

Study 2025 is an on-going open-label Phase 2 study evaluating the efficacy and safety of sofosbuvir (SOF) 400 mg once daily plus weight-based ribavirin (RBV) for up to 48 weeks or until liver transplantation. Sixty-one patients with HCV infection (Child-Pugh class A or B cirrhosis) and liver cancer, who were either treatment-naïve or treatment-experienced were enrolled.

About the Post-Transplant Study

Study 0126 is an ongoing open-label Phase 2 study evaluating the efficacy and safety of 24 weeks of treatment with sofosbuvir 400 mg once-daily plus RBV (starting at 400 mg/day) among 40 treatment-naïve and treatment-experienced patients with recurrent HCV infection. Patients in the study had received a transplant a median of four years prior to the study, and 40 percent were cirrhotic.

There were no deaths, graft losses or episodes of organ rejection among post-liver transplantation patients in the study.

Additional information about these studies can 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 the possibility of unfavorable longer-term results from Studies 025 and 126 and other ongoing and subsequent clinical trials involving sofosbuvir, alone or in combination with other products, for the treatment of HCV. In addition, regulatory authorities will 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. Further, 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)

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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 64^th 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)

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Gilead Announces Phase 3 Results for an All-Oral, Sofosbuvir-Based Regimen for the Treatment of Hepatitis C in Patients Co-Infected With HIV

WASHINGTON--(BUSINESS WIRE)--Nov. 2, 2013-- Gilead Sciences, Inc. (Nasdaq:GILD) today announced results from a Phase 3 study, PHOTON-1, evaluating the investigational once-daily nucleotide analogue sofosbuvir for the treatment of chronic hepatitis C virus (HCV) infection among patients co-infected with HIV. In the trial, 76 percent (n=87/114) of genotype 1 HCV treatment-naïve patients receiving 24 weeks of an all-oral, interferon-free regimen of sofosbuvir plus ribavirin (RBV) achieved a sustained virologic response 12 weeks after completing therapy (SVR12). Patients who achieve SVR12 are considered cured of HCV infection. These data will be presented this week during the 64^th Annual Meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2013) in Washington, D.C.

Up to one-third of people living with HIV in the United States are co-infected with HCV. Current HCV medicines are associated with suboptimal cure rates among co-infected patients and can cause significant interactions with HIV drugs.

“There is a clear need for HCV treatment regimens that are more effective and safer for patients who are co-infected with HIV,” said Douglas Dieterich, MD, Professor of Medicine in the Division of Liver Diseases and Director of Continuing Medical Education in the Department of Medicine at Mount Sinai School of Medicine. “In this study, sofosbuvir-based all-oral therapy achieved high SVR rates in a hard-to-treat patient population. This regimen may have the potential to help us overcome the clinical challenge of treating HCV/HIV co-infection.”

PHOTON-1 also assessed 12 weeks of sofosbuvir plus RBV among genotype 2 and 3 HCV treatment-naïve patients with HIV. Among genotype 2 patients receiving this regimen, 88 percent (n=23/26) achieved SVR12, while 67 percent (n=28/42) of genotype 3 patients achieved SVR12. All patients in PHOTON-1 who did not achieve SVR12 had viral relapse after cessation of therapy, with the exception of two participants who were non-adherent to study drugs.

Treatment discontinuations due to adverse events were reported in three percent of patients receiving 24 weeks of therapy and four percent of patients receiving 12 weeks of therapy. The most common side effects observed in the study were consistent with the safety profile of RBV and included fatigue, nausea, headache and insomnia.

About PHOTON-1

PHOTON-1 is an ongoing open-label Phase 3 study being conducted at sites in the United States and Puerto Rico to evaluate the efficacy and safety of 12 or 24 weeks of sofosbuvir 400 mg once-daily plus weight-based RBV (1,000 or 1,200 mg/day) among HCV treatment-naïve patients with genotype 1, 2 or 3 HCV infection who are also HIV-positive.

Ninety-five percent of PHOTON-1 patients were receiving antiretroviral therapy for their HIV infection. The HIV treatment regimens permitted in the study were based on the results of a separate Phase 2 drug-drug interaction study conducted by Gilead demonstrating that sofosbuvir did not significantly affect the pharmacokinetic parameters of drugs from various classes of antiretrovirals. The most common HIV treatment regimens taken by patients in PHOTON-1 were Gilead’s Truvada^® (emtricitabine/tenofovir disoproxil fumarate) administered with efavirenz, atazanavir/ritonavir, darunavir/ritonavir or raltegravir.

Additional information about PHOTON-1 can 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 the possibility of unfavorable longer-term resulting from clinical trials evaluating sofosbuvir, including in combination with other products and among patients with HCV/HIV co-infection or HCV monoinfection. In addition, 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. Further, 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.

U.S. full prescribing information for Truvada is available at www.gilead.com.

Truvada is a registered trademark of Gilead Sciences, Inc.

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

Source: Gilead Sciences, Inc.

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

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BMS Submits First All-Oral, Interferon-Free and Ribavirin-Free Treatment Regimen for Regulatory Review in Japan for Patients with Chronic Hepatitis C Infection

• An overall SVR₂₄ rate of 84.7% was achieved in Phase III study of daclatasvir (DCV) and asunaprevir (ASV) in high unmet need genotype 1b patient population
• DCV+ASV achieved 87.4% SVR₂₄ rates in interferon-ineligible/intolerant patients and 91.9% SVR₂₄ among this population aged 65+, providing potential treatment alternative for many in Japan who currently have no options
• In this study, the DCV+ASV regimen had low rates of discontinuation (5%) due to adverse events, and low rates of serious adverse events (5.9%)
• Data presentation will lead AASLD Viral Hepatitis Presidential Plenary session on Tuesday, November 5

Saturday, November 2, 2013 9:00 am EDT

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE: BMY) today announced the submission of a New Drug Application (NDA) to Japan’s Pharmaceutical and Medical Devices Agency seeking the world’s first interferon-free and ribavirin-free treatment regimen for patients with chronic hepatitis C. The submission is based on results from a Phase III study demonstrating that the 24-week, all-oral, interferon-free and ribavirin-free regimen of daclatasvir (DCV) and asunaprevir (ASV) achieved an overall sustained virologic response 24 weeks after the end of treatment (SVR₂₄) of 84.7% in Japanese patients with chronic hepatitis C (HCV) genotype 1b who were either interferon-ineligible/intolerant (87.4% SVR₂₄) or non-responders (null and partial) to interferon-based therapies (80.5% SVR₂₄).

These Phase III data will lead the Presidential Plenary at the Viral Hepatitis Session on November 5 during the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington D.C.

Globally, there are 170 million people who are infected with HCV. Of the 1.2 million people living with HCV in Japan, approximately 70 percent of these patients have genotype 1b, which has one of the lowest response rates to current treatments. Further, a significant number of patients with HCV in Japan are over the age of 65, leading to more disease-related complications and a decreased likelihood of tolerating interferon-based therapies, the standard for treating HCV.

“With our submission in Japan, we are pleased to be one step closer to bringing a potential new treatment option to the many people living with HCV in that country,” said Brian Daniels, MD, senior vice president, Global Development and Medical Affairs, Research and Development, Bristol-Myers Squibb. “The all-oral regimen of DCV plus ASV in this study represents the potential for a significant advance in the treatment of HCV infection in Japan, particularly when considering that Japanese patients chronically infected with HCV are often older than in other countries and predominantly infected with genotype 1b, both factors which impact response to therapy.”

The regimen used in the Phase III study resulted in low rates of discontinuation (5%) due to adverse events (AEs). In addition, the rate of serious adverse events (SAEs) was low (5.9%) and varied among patients. Nasopharyngitis was the most common adverse event in the study (30.2%, 67/222).

Study Design and Results

In this open-label, parallel group, Phase III study, interferon- ineligible/intolerant (IN/I) patients (n=135) and interferon/ribavirin non-responder (NR) patients (n=87) received DCV 60 mg once daily plus ASV 100 mg twice daily for 24 weeks. The primary endpoint was the percentage of patients with a sustained virologic response at 24 weeks after the end of treatment (SVR₂₄).

Virologic Response

• High rates of SVR₂₄ were achieved in the two studied patient populations – those IN/I patients with limited therapeutic options (87.4%, 118/135) and those NR patients typically associated with low responses to interferon-based therapies (80.5%, 70/87).
• Patients ≥ 65 years of age had SVR₂₄ rates similar to those in patients < 65 years and age did not appear to impact response rates. SVR₂₄ rates for those ≥ 65 years of age were 91.9% (57/62) in the IN/I elderly patient population and 85.2% (23/27) in the NR elderly population.
• There was no clinically significant difference in SVR₂₄ by traditionally important baseline factors including gender, age, baseline HCV RNA, cirrhosis, and IL28B genotype.
• There were low rates of virologic breakthrough and EOT (end of treatment) detectable HCV RNA (17/222 patients (7.7%)), and low rates of relapse (17/205 patients (8.3%)).

“The Phase III study results of daclatasvir plus asunaprevir are exciting to see, especially in this difficult-to-treat patient population. If approved, this regimen has the potential to offer HCV patients in Japan, who are unable to achieve SVR with the current interferon-based standard of care, a new treatment option,” said lead study investigator Kazuaki Chayama of Hiroshima University, Japan.

On-Treatment Safety

No deaths were reported and the study discontinuation rate was low (12.6%, 28/222). There were low rates of serious adverse events (5.9%, 13/222) and few adverse events were reported in greater than 10% of patients. The most common adverse events reported were nasopharyngitis (30.2%, 67/222), increased ALT (15.8%), increased AST (12.6%), headache (15.8%), diarrhea (9.9%) and pyrexia (12.2%). A limited number of Grade 3-4 laboratory abnormalities were observed in greater than 3 percent of patients.

The most common adverse event leading to discontinuation was ALT/AST elevation, a measure of liver inflammation. Of the 11 patients who discontinued due to an adverse event, 10 discontinued due to ALT/AST elevation. Despite early discontinuation, 80% of these patients achieved SVR₂₄ and all ALT/AST values returned to normal.

About Bristol-Myers Squibb’s HCV Portfolio

Bristol-Myers Squibb’s hepatitis C pipeline includes compounds with different mechanisms of action, pursuing both biologics as well as small molecule direct-acting antivirals. These compounds are being studied as part of multiple treatment regimens with the goal of increasing SVR rates across diverse patient types and geographies.

• Our investigational NS5A replication complex inhibitor daclatasvir (DCV) has been extensively studied in thousands of patients to date as a foundational agent for multiple direct-acting antiviral-based (DAA) combination therapies. DCV has shown antiviral potency and pan-genotypic activity across HCV genotypes in vitro. DCV has a drug-drug interaction profile that supports its continued study in a variety of HCV combination regimens
• Asunaprevir (ASV) is an investigational NS3 protease inhibitor for hepatitis C which has been studied as a component of DCV-based treatment regimens
• BMS-791325 is a non-nucleoside inhibitor of the NS5B polymerase, currently in Phase II development for hepatitis C as a component of DCV-based treatment regimens
• Lambda is an investigational type III interferon that has the potential to offer an alternative to alfa-interferon in patients for whom an interferon-based regimen is required or preferred

About Hepatitis C

Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. An estimated 170 million people worldwide are infected with hepatitis C, with genotype 1 being the most prevalent genotype. Up to 90 percent of those infected with hepatitis C will not clear the virus and will become chronically infected. According to the World Health Organization, 20 percent of people with chronic hepatitis C will develop cirrhosis and, of those, up to 25 percent may progress to liver cancer. In Japan, the hepatitis C virus is the most common cause of chronic hepatitis and cirrhosis, and approximately 1.2 million people there are living with the hepatitis C virus.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Bristol-Myers Squibb Forward Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that the clinical trials of these compounds will support regulatory filings, or that the compounds described in this release will receive regulatory approvals or, if approved, that they will become commercially successful products. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2012, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

Contact:

Bristol-Myers Squibb
Media:
Carrie Fernandez, 215-859-2605
carrie.fernandez@bms.com
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Julie Ferguson, 312-385-0098
julie.ferguson@bms.com
or
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Ranya Dajani, 609-252-5330
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or
Ryan Asay, 609-252-5020
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Achillion's Uridine-Analog Nucleotide Prodrug, ACH-3422, Shows Compelling Preclinical Profile

November 2, 2013

New Preclinical Data Being Presented at The Liver Meeting 2013

NEW HAVEN, Conn., Nov. 2, 2013 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced a poster presentation detailing the preclinical profile of ACH-3422, a uridine-analog nucleotide prodrug being advanced for the potential treatment of chronic hepatitis C viral infection (HCV). The poster is being presented at the 64^th Annual Meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2013) in Washington D.C.

The poster presentation, entitled, "Preclinical Characteristics of ACH-3422: A Potent Uridine Nucleotide Prodrug for Inhibition of Hepatitis C Virus NS5B RNA Polymerase," (Poster 475; HCV Therapy: The Developmental Pipeline. Saturday, November 2, 2013: 2:00 PM — 7:30 PM ET. Poster Hall), details the potent and specific inhibition of HCV NS5B polymerase by ACH-3422, and the demonstrated low risk for mitochondrial toxicity based upon in vitro studies with human cells in static and proliferating conditions, and high efficiency in the conversion of ACH-3422 into the triphosphate within human hepatocyte cell lines. These attributes, combined with the previously reported 14-day animal toxicity study of ACH-3422, continue to support the advancement of this compound toward clinical studies for use in combination with other direct acting antiviral agents for the potential pan-genotypic treatment of chronic HCV.

"These data provide additional insight into the compelling profile of ACH-3422 as a potential NS5B nucleotide inhibitor for the broad treatment of HCV. Based upon our current development timelines, we anticipate initiating our first-in-human and proof-of-concept trials with ACH-3422 during the first half of 2014," commented Milind Deshpande, Ph.D., President and Chief Executive Officer of Achillion. "We believe that the ability to potentially combine a potent nucleotide, such as ACH-3422, with our other proprietary assets, including our differentiated Phase 2 NS5A inhibitor, ACH-3102, and our Phase 2 protease inhibitors, including ACH-2684, provides extensive optionality for developing a simple and effective all-oral treatment regimen aimed at curing HCV across broad treatment populations."

A reprint of the poster presentation can be accessed from the Resources section of our website at http://www.achillion.com.

About ACH-3422

ACH-3422 is a small-molecule, nucleotide prodrug inhibitor of HCV NS5B polymerase. In vitro, ACH-3422 has demonstrated excellent potency, with activity demonstrated across all genotypes of HCV and an EC₅₀ of approximately 50 to 65 nanomolar against genotype 1 HCV. To date, Achillion has completed 14-day safety studies in animals, where no significant findings were noted at the highest dose tested. ACH-3422 appears to have high oral bioavailability, rapid uptake and conversion of the prodrug into the monophosphate within the liver, and a pharmacokinetic profile supportive of once-daily dosing. Manufacturing and preclinical studies to support clinical development have been initiated, with the expectation of beginning first-in-human studies during the first half of 2014.

About Achillion Pharmaceuticals

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's discovery, clinical development, and commercial teams have advanced multiple novel product candidates with proven mechanisms of action into studies and toward the market. Achillion is focused on solutions for the most challenging problems in infectious disease including HCV and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.

Cautionary Note Regarding Forward-Looking Statements

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 important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including statements with respect to: the potential favorable potency, safety, efficacy and other attributes of ACH-3422 and its potential benefits when used in combination with other direct acting antiviral agents to treat HCV; and the Company's plans and timing for progressing ACHN-3422 into clinical development. We may use words such as "expect," "anticipate," "project," "intend," "plan," "believe," "seek," " estimate," and "may" and similar expressions to identify such forward-looking statements. Among the important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: demonstrate in any potential future clinical trials the requisite safety, efficacy and combinability of ACH-3422; advance the preclinical and clinical development ACH-3422 and its other drug candidates, including ACH-3102, and ACH-2684, under the timelines it projects in current and future clinical trials; satisfactorily respond to the clinical hold placed on sovaprevir by the FDA; obtain and maintain necessary regulatory approvals; obtain and maintain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; manage litigation; raise the substantial additional capital needed to achieve its business objectives; and successfully execute on its business strategies. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the fiscal quarter ended June 30, 2013 and its subsequent SEC filings.

In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any duty to update any forward-looking statement, except as required by applicable law.

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

WASHINGTON, Nov. 2, 2013 /PRNewswire/ -- 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-naive and treatment-experienced adult patients with compensated liver disease. In analyses of the Phase 3 QUEST-1 and QUEST-2 studies in treatment-naive 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 IL28B TT 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-naive 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.

(This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995.  The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events.  If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen R&D Ireland, any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson.  Risks and uncertainties include, but are not limited to, general industry conditions and competition; economic factors, such as interest rate and currency exchange rate fluctuations; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; challenges to patents; impact of business combinations; changes in behavior and spending patterns or financial distress of purchasers of health care products and services; changes to governmental laws and regulations and domestic and foreign health care reforms; trends toward health care cost containment; and increased scrutiny of the health care industry by government agencies.  A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 30, 2012.  Copies of this Form 10-K, as well as subsequent filings, are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson.  None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertake to update any forward-looking statements as a result of new information or future events or developments.)

Media Contact: Daniel De Schryver               
Mobile: +49 173 76 89 149

Media Contact: Craig Stoltz               
Mobile: +1 (215) 325-3612

Investor Contact: Stan Panasewicz                      
Office: +1 (732) 524-2524

Investor Contact: Louise Mehrotra                        
Office: +1 (732) 524-6491    

SOURCE Janssen R&D Ireland

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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

Saturday, November 2, 2013 9:00 am EDT

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).

Contact:

Merck
Media:
Pamela Eisele, (908) 423-5042
Sarra Herzog, (908) 423-6154
or
Investor:
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Justin Holko, (908) 423-5088

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Gilead Sciences and Johnson & Johnson Push Vertex Out of Hepatitis C Race

Provided by The Motley Fool

By Amy Ho | More Articles
November 1, 2013

Following significant moves toward FDA approval for two hepatitis C agents last week -- sofosbuvir by Gilead Sciences  (NASDAQ: GILD ) and simeprevir by Johnson & Johnson (NYSE: JNJ )  -- competitor Vertex Pharmaceuticals (NASDAQ: VRTX ) is cutting jobs associated with its hepatitis C drug and changing focus to the hopefully more profitable and less competitive cystic fibrosis space.

Vertex knew this day was coming, as the race to a new hepatitis C treatment has had major players Gilead, Bristol-Myers Squibb, AbbVie, and Johnson & Johnson long vying for a new interferon-free agent.

Vertex's Incivek is a first-generation oral agent against hepatitis C that is still used in combination with interferon and thus is not completely interferon-free (which is the ultimate goal for new therapeutics, given the unpleasant flu-like side effects of interferon). Incivek, as well as Merck's Victrelis were both approved in 2011 as protease inhibitors to stop replication of the hepatitis C virus; the new agents coming down the pipeline work under a similar mechanism, but better and with potential to be independent of interferon.

While now clearly a short-term asset, Incivek was quite successful at initial release. Sales peaked at $456.8 million in 2011 and helped Vertex reach profitability. However, as physicians stopped starting new patients on the agent, waiting for newer agents to gain approval, Incivek sales quickly declined. This past quarter alone, sales were down 66%. The company is on a $124.1 million loss this quarter, and the 15% workforce cut and restructuring is expected to product a $150 million to $200 million reduction in operating expenses this year.

Meanwhile, Gilead is investing $47 million and 80 jobs for the manufacturing of sofosbuvir, which achieved a unanimous recommendation from a panel of experts at the FDA last week. While sofosbuvir was tested in conjunction with interferon, it is expected to be the first-in-class oral, interferon-free hepatitis C treatment. Peak annual sales are estimated at $7 billion.

J&J's simeprevir also got unanimous support from an FDA panel, although it targets a narrower class of genotypes for hepatitis C. Both drugs will likely gain FDA approval this year. To seal the coffin, Bristol-Myers Squibb and AbbVie are both expected to file New Drug Applications next year and around 20 agents are in the hepatitis C pipeline.

It is no wonder Vertex is moving away for this quickly crowded space. In the release announcing the cost-cutting measures, CEO Jeffrey Leiden indicated his vision for opportunity in cystic fibrosis. Most likely he was referring to Kalydeco, a treatment for the genetic disease that was approved last year. So far, its 2013 total sales are growing at $261 million, already well surpassing the $171 million in total 2012 sales. Sales more than doubled for Kalydeco this quarter, to $101.1 million and Vertex's force for 2013 is $365 million in sales.

While a smart move, the shift will still likely take a toll just due to the smaller market for cystic fibrosis. Around 170 million people are infected worldwide with hepatitis C, as opposed to about 70,000 worldwide for cystic fibrosis. Patients can live a normal lifespan with hepatitis C, whereas cystic fibrosis is longevity-limiting -- the median age of survival for cystic fibrosis is in the 30s.

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Gilead's Hepatitis C Drug Continues to Impress

Fri, 11/01/2013 - 12:00pm

Gilead's new drug therapies continue to show promise for some hepatitis C sufferers whose transplanted livers are threatened by a recurrence of the disease, including some patients who have had no treatment options.

These encouraging findings are contained in two new studies by a collaboration of researchers across the U.S.—as well as in Spain and New Zealand—including Dilip Moonka, MD, medical director of Liver Transplant at Henry Ford Hospital. Both studies are being presented at the annual meeting of the American Association for the Study of Liver Disease being held in Washington, DC, Nov. 1-5.

The studies focused on Gilead Pharmaceutical’s experimental anti-viral drug sofosbuvir, a direct-acting oral medication that may take the place of injectable interferon, which causes severe side effects in some patients.

The U.S. Food and Drug Administration is expected to decide in early December whether to approve its use for treating hepatitis C. Last week, the Antiviral Drugs Advisory Committee of the FDA voted unanimously in support of approval for sofosbuvir-based therapies for the treatment of chronic hepatitis C.

Chronic hepatitis C is a blood-borne viral disease that leads to scarring and deterioration of the liver. It is particularly insidious because patients usually don't develop symptoms until the scarring—or cirrhosis—is well underway.

Sofosbuvir, which belongs to a class of drugs known as nucleotide analogue polymerase inhibitors, acts at the molecular level by interfering with the RNA of the hepatitis C virus.

Interferon alternative
In the first newly released study, researchers tested it as an alternative to interferon, a naturally occurring protein that plays a role in fighting viral infections, but commonly produces a range of serious side effects.

The researchers used it in combination with ribavirin, which also inhibits the hepatitis C virus by interfering with its RNA to stem the replication of the virus and slow the progression of the disease. They sought to test the drug combination's effectiveness in preventing recurrence of hepatitis C in liver transplant recipients.

A total of 61 chronic hepatitis C patients with liver cancer were enrolled in the study and given both sofosbuvir and ribavirin daily for up to 48 weeks before liver transplant. All of the patients had well-compensated cirrhosis, meaning their bodies were still functioning without too much trouble despite liver scarring.

The researchers found that the new drug combination was both safe and effective in such patients and prevented post-transplant recurrence of the hepatitis C virus in more than 60 percent of them.

No other option
In the second newly released study, researchers focused on liver transplant recipients whose severe hepatitis C recurred after surgery and who either couldn't tolerate or didn't respond to approved antiviral therapies—leaving them with no other effective treatment options.

In such cases, experimental drugs can sometimes be tested under "compassionate use" protocols.

The researchers reported that as of April, 115 patients were approved for compassionate use of sofosbuvir combined with ribavirin and/or the anti-viral drug peginterferon. At the time of their report, 63 had started treatment.

After several weeks of treatment and study, the researchers concluded that patients with severe recurrence of hepatitis C after receiving transplanted livers were able to tolerate the drug regimen, which produced strong anti-viral effects.

Date: October 31, 2013
Source: Henry Ford Health System

Source

Also See:

• Studies of Experimental Hepatitis C Drug Show Promise for Preventing Recurrence in Liver Transplant
• Current Hepatitis C Treatments Can't be Used by More Than Half of Patients

Prison needle exchange programs rare despite evidence

October 29, 2013

Although the UN and WHO advocate for needle and syringe exchanges for inmates, only 60 prisons of more than 10 000 worldwide have programs.

Photo Credit: © 2013 Thinkstock

Clean needle distribution in prisons is "poor and patchy" around the world, despite evidence that it reduces the spread of infectious diseases and does not increase drug use, an international expert told a panel discussion in Toronto, Ontario.

"There's a big gap between what is being recognized at the UN [United Nations] level and what is going on, on the ground," Heino Stöver, a professor at the University of Applied Sciences in Frankfurt, Germany, recently told an audience at the Dalla Lana School of Public Health.

Although the United Nations Office on Drugs and Crime and the World Health Organization (WHO) both advocate for needle and syringe exchanges for inmates, only 60 prisons out of more than 10 000 worldwide have launched programs since Switzerland set up the first one in 1994, said Stöver. Switzerland, Spain, Kyrgyzstan, Moldova, Romania, Portugal and Luxembourg all have needle exchange programs in at least one prison.

Germany ended six of its seven programs in the past decade. "They were politically controversial but not professionally controversial. We have very fine evidence that they were working," said Stöver, who has advocated for prison needle exchanges since he was "a young man … throwing syringes over the prison walls."

A WHO review of 55 European prison needle exchange programs found no reported increase in drug use and no negative unintended consequences. No needles were used as weapons, for example.

Among Canadian inmates, 30% of males and 34.9% of females have contracted Hepatitis C, compared to .95% of men and .61% of women in the general population. The figures for inmates are based on Correctional Service Canada's 2008 statistics, the most recent available, compared with 2007 figures for the general population. For HIV, the rates are 1.7% (males) and 4.7% (females), compared to 0.2% in the Canadian population.

Canada does not offer needle exchange programs in any prison. The absence of such programs is the subject of a current lawsuit that prisoner, HIV/AIDS and Aboriginal advocacy groups have launched. They hope a successful suit will force federal prisons to implement needle exchanges.

Correctional Service Canada "has a comprehensive anti-drug strategy ... providing needles for illicit drug use run counter to that strategy," spokesperson Melissa Hart writes in an email.

The lawsuit argues that prisoners are entitled to the same standards of essential health care as in the wider community, and that the 200 needle exchange programs available across Canada are part of this essential health package, says Lisa Kerr, a lawyer and academic who studies approaches to incarceration and justice.

In addition, lawyers have pointed to the Canadian Charter of Rights and Freedoms, arguing dirty needles in prisons makes life worse for indigenous people, for women, and for people with disabilities, Kerr told the panel in Toronto. Indigenous people, who make up 4% of the Canadian population, account for 23% of the prison population.

Current methods of reducing infections have shortcomings. Machines that dispense bleach and condoms, for example, are sometimes located near cameras and prisoners worry about increased surveillance if they use them. The dispensing machines are also frequently empty, said Seth Clarke, the community development coordinator for the Prisoners' HIV/AIDS Support Action Network.

Furthermore, bleach is not 100% effective in eliminating Hepatitis C, and the "best practice" method of cleaning, rinsing and cleaning again is not pragmatic for the "quite hastily" way prisoners  use needles, Clarke said. After all, drug use and tattooing are both illegal in prisons.

In addition to providing needle exchange programs, prison authorities should help rather than punish addicts, argued Clarke. For example, when a prisoner recently turned in his needle because he wanted to stop using, he was slapped with an institutional charge. "This kind of thing happens all the time," he said.

In a taped interview aired during the presentation, one former prisoner said that inmates construct needles out of "markers, light bulb filaments [and] the inside of a pen tube," and often share them. Injectable drugs are popular, he said, because "it's the biggest bang for your buck."

As to how the drugs are getting into prisoners, Clarke answered indirectly, noting that family members and friends often face drug dogs and careful searches but "they're not doing that for staff a lot of the time."

DOI:10.1503/cmaj.109-4644

— Wendy Glauser, Toronto, Ont

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