Conatus Pharmaceuticals Presents Late-Breaking Poster at AASLD Annual Meeting

Key Biomarker Data From Phase 1 Trial of Emricasan in Patients With Hepatic Impairment

SAN DIEGO, Nov. 10, 2014 (GLOBE NEWSWIRE) -- Conatus Pharmaceuticals Inc. (Nasdaq:CNAT) today is presenting its late-breaking poster at The Liver Meeting®, the annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston November 7-11, 2014. The poster (#LB16), entitled "Rapid and statistically significant reduction of markers of apoptosis and cell death in subjects with mild, moderate and severe hepatic impairment treated with a single dose of the pan-caspase inhibitor, emricasan," will be available for viewing in the Poster Hall on the second floor of the John B. Hynes Convention Center today, Monday, November 10, 2014, from 8:00 a.m. to 5:30 p.m. ET and authors will be available for discussion at the poster from 12:30 p.m. to 2:00 p.m. ET. The poster is available on the Events & Presentation page in the Investor Center of the Conatus website at www.conatuspharma.com.

The poster highlights key secondary endpoint pharmacodynamic (PD) biomarker results from the company's recently completed Phase 1 hepatic impairment clinical trial. The trial was conducted in 12 subjects with mild, 8 subjects with moderate, and 8 subjects with severe hepatic impairment, as defined using Child-Pugh Scores, and 8 healthy matched control subjects. All subjects received a single 50 mg oral dose of emricasan, and serial blood samples were collected over a 48-hour period. Levels of three key biomarkers of apoptosis, overall cell death, and caspase enzymatic activity – caspase-cleaved cytokeratin 18 (cCK18), full-length cytokeratin 18 (flCK18), and caspase 3/7, respectively – were elevated at study baseline and demonstrated rapid and statistically significant reductions after a single 50 mg oral dose of emricasan. Importantly, levels of these three key biomarkers demonstrated significant reductions from the elevated levels at baseline in 100% of the hepatic impaired subjects compared with 0% of the matched control subjects, whose baseline levels were not elevated. In all three impaired groups, peak reductions of caspase 3/7 occurred approximately 4 hours after dosing, and peak reductions in cCK18 and flCK18 levels occurred 8 to 12 hours after dosing. All three biomarkers trended toward pre-dose levels within 24 to 48 hours after dosing. Noteworthy conclusions from the study included:

• Mechanism-specific biomarkers of apoptosis and caspase enzymatic activity, together with a biomarker of overall cell death, are elevated in subjects with advanced liver disease.
• Biomarker elevations were rapidly reduced after a single dose of emricasan in all hepatic impaired patients.
• Since elevation of these biomarkers is related to disease pathology and progression, emricasan may provide clinical benefit to patients with advanced stages of liver disease.

"We had previously demonstrated emricasan's ability to rapidly reduce disease-elevated biomarkers of caspase activity, apoptosis and overall cell death in patients with earlier-stage liver disease," said Conatus co-founder, Senior Vice President of Research and Chief Scientific Officer, Alfred P. Spada, Ph.D., "and we are pleased that the current study showed significant and rapid reductions in these biomarkers after a single dose of emricasan in patients in more advanced stages of liver disease. We believe these biomarkers measure key drivers in the progression of liver disease, and we look forward to completing our ongoing trials to determine whether biomarker reductions correlate with clinical benefits for patients."

Conatus initiated three clinical trials of emricasan in patients with impaired organ function to support dose selection and prioritization for advancement in its overall clinical development program: a Phase 2b trial initiated in September 2013 in acute-on-chronic liver failure (ACLF) patients who may have simultaneous impairment of both liver and kidney function; a Phase 1 trial initiated in January 2014 in patients with severe renal impairment; and the previously described Phase 1 hepatic impairment trial initiated in April 2014. Preliminary pharmacokinetic (PK) results from the renal impairment and hepatic impairment trials were used to support the design of two recently initiated trials in patients with liver cirrhosis. Aggregate final data from these three trials are expected to be sufficient to inform on optimal dosing of emricasan, and future direction for the clinical development of emricasan, in potential future studies over a broad range of patient populations, including critically ill patients with varying degrees of liver and kidney function.

About Emricasan Clinical Development

Conatus is developing emricasan for the treatment of patients with chronic liver disease and acute exacerbations of chronic liver disease, including ACLF, liver cirrhosis (LC), portal hypertension (PH), post-orthotopic liver transplant (POLT) recipients with reestablished liver fibrosis post-transplant as a result of recurrent hepatitis C virus (HCV) infection who have successfully achieved a sustained viral response (SVR) following HCV antiviral therapy (POLT-HCV-SVR), and nonalcoholic fatty liver disease (NAFLD), including patients with inflammatory and/or fibrotic nonalcoholic steatohepatitis (NASH). Conatus is also supporting a pilot clinical study funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in patients with severe alcoholic hepatitis. To date, emricasan has been studied in over 550 subjects in twelve clinical trials.

About Conatus Pharmaceuticals

Conatus is a biotechnology company focused on the development and commercialization of novel medicines to treat liver disease. Conatus is developing its lead compound, emricasan, for the treatment of patients with chronic liver disease and acute exacerbations of chronic liver disease. Emricasan is a first-in-class, orally active pan-caspase protease inhibitor designed to reduce the activity of enzymes that mediate inflammation and cell death, or apoptosis. Conatus believes that by reducing the activity of these enzymes, emricasan has the potential to interrupt the disease progression across the spectrum of liver disease. For additional information, please visit www.conatuspharma.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward-looking statements, including statements regarding the elevation of biomarkers related to liver disease pathology and progression, emricasan's potential to impact on the biomarkers and the progression of liver disease, the potential for the PK data to inform on optimal dosing of emricasan in future studies in potential target patient populations, the role of caspase activity and apoptosis in disease pathology and progression, and emricasan's potential to provide clinical benefit to patients across a broad spectrum of liver disease, including patients with advanced stages of liver disease. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "anticipate," "could," "intend," "target," "project," "contemplates," "believes," "estimates," "predicts," "potential" or "continue" or the negative of these terms or other similar expressions. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including:  dosing of emricasan beyond a single dose, the applicability of the biomarkers as potential drivers of liver disease progression, the effect on liver disease of decreasing the biomarkers, the determination of the most appropriate patients for enrollment in the company's Phase 2 clinical trial in patients with cirrhosis, the potential for competing products to limit the clinical trial enrollment in the company's Phase 2 clinical trials, the company's ability to successfully enroll patients in and complete its Phase 2 clinical trials; the company's reliance on third parties to conduct its clinical trials, including the enrollment of patients, and manufacture its clinical drug supplies of emricasan; potential adverse side effects or other safety risks associated with emricasan that could delay or preclude its approval; results of future clinical trials of emricasan; the company's ability to obtain additional financing in order to complete the development and commercialization of emricasan; and those risks described in the company's prior press releases and in the periodic reports it files with the Securities and Exchange Commission. The events and circumstances reflected in the company's forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Except as required by applicable law, the company does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

Alan Engbring
(858) 376-2637

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Arrowhead Presents Data on ARC-520 and ARC-AAT at AASLD The Liver Meeting® 2014

- ARC-520 shows statistically significant reduction in HBsAg through day 43 after a single injection (p < 0.05)

- Repeat dosing of ARC-AAT in primates shows reduction of approximately 90% of serum alpha 1 antitrypsin (AAT) with long duration of effect suggesting that monthly or less frequent dosing may be sufficient for sustained suppression of hepatic AAT production

- ARC-AAT abstract highlighted in the AASLD President’s Press Conference as a promising new treatment

- Arrowhead will host an investor event and presentation to discuss results that will be webcast at 8:00 p.m. EST

November 10, 2014 09:15 AM Eastern Standard Time

AASLD 2014

PASADENA, Calif.--(BUSINESS WIRE)--Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical company developing targeted RNAi therapeutics, today announced that initial data from the ongoing Phase 2a study of ARC-520, its RNAi therapeutic candidate for the treatment of chronic hepatitis B (HBV) infection, was presented today in the late-breaking poster session at the 2014 American Association for the Study of Liver Diseases (AASLD) Liver Meeting in Boston. Arrowhead also delivered a plenary presentation with new preclinical efficacy data on ARC-AAT, its RNAi therapeutic candidate for the treatment of liver disease associated with Alpha-1 antitrypsin deficiency.

“We presented some important advancements today for both ARC-520 and ARC-AAT”

The Company will host an investor event and presentation to discuss these results that will be webcast tonight at 8:00 p.m. EST. Investors may access the webcast and presentation slides on the Events page of the Company’s website at http://ir.arrowheadresearch.com/events.cfm. An audio only version of the live webcast may also be accessed by calling 844-825-4406 toll-free from the U.S., or 315-625-3230 for international callers, using conference ID 31449966. An archive of the call will be available for seven days and may be accessed by calling 855-859-2056 or 404-537-3406. Copies of the AASLD poster and plenary presentation will also be available to view on the Events page of the Company’s website.

“We presented some important advancements today for both ARC-520 and ARC-AAT,” said Christopher Anzalone, Ph.D., Arrowhead’s President and Chief Executive Officer. “These programs and our expanding pipeline of RNAi therapeutics continue to generate exciting data that further validate the utility of the DPC delivery system. We have seen clear activity across multiple preclinical models and are now seeing activity in humans. We are still dose escalating in the ARC-520 Phase 2a, where dosing is complete in the 3 mg/kg cohort and screening has begun for 4 mg/kg. We believe that the initial data from the first two dose cohorts as well as safety data from the Phase 1 volunteer study are encouraging and support advancement of the program into multi-dose Phase 2b studies. We are currently preparing regulatory filings for the ARC-520 Phase 2b and the ARC-AAT Phase 1, both of which we expect to be filed this quarter. We intend to initiate those studies soon after receiving regulatory permission to begin.”

ARC-520 Data

In a Late-Breaking Poster titled, “Phase II, dose ranging study of ARC-520, a siRNA-based therapeutic, in patients with chronic hepatitis B virus infection,” interim data on ARC-520 was presented by Man-Fung Yuen, M.D., Ph.D., Chair of Gastroenterology and Hepatology, and Li Shu Fan Medical Foundation Professor in Medicine, The University of Hong Kong, and a principal investigator for the study. The poster included up-to-date safety data on ARC-520 from this study, an ongoing Phase 2a multicenter, randomized, double-blind, placebo-controlled, dose-escalation study, as well as a recently completed Phase 1 normal volunteer study.

The nine dose group, Phase 1, normal volunteer trial was designed to characterize the safety profile of ARC-520 across a range of doses and evaluate pharmacokinetics. It was a single-center, randomized, double-blind, placebo-controlled, single dose-escalation, first-in-human study of ARC-520 administered intravenously to healthy adult volunteers for which partial data has been previously reported. All subjects received either placebo or ARC-520 in doses ranging from 0.01 mg/kg to 4.0 mg/kg. The study successfully enrolled all 54 subjects (36 received ARC-520, 18 placebo). The Phase 2a study has enrolled three dose cohorts including 24 patients, 18 receiving drug and 6 receiving placebo. Unblinded data is available for the first two cohorts. Cohort 3 data collection is ongoing and this cohort remains blinded. Full results for the first two dose cohorts at 1.0 mg/kg and 2.0 mg/kg and partial (blinded) safety results from the 3.0 mg/kg dose cohort were included in the poster.

In both studies, there have been no reports of serious AEs, no dose limiting toxicities, no discontinuations due to AEs, and a modest overall occurrence rate of AEs without a clear dose-related increase in frequency or severity. There has been a modest occurrence rate of non-clinically significant abnormal laboratory tests. There were no reported drug related or clinically significant differences for vital signs or ECGs between subjects receiving drug versus placebo. To date, ARC-520 when administered as a single dose up to 4.0 mg/kg to healthy volunteers and up to 3.0 mg/kg to patients with chronic HBV appears to be well tolerated.

Arrowhead also reported initial results for depth and duration of hepatitis B surface antigen (HBsAg) reduction in the Phase 2a study. In cohort 1 (1.0 mg/kg), the mean nadir of HBsAg was -39% (range -22 to -57) with a mean change on day 85 of -31% (range -14 to -39). In cohort 2 (2.0 mg/kg), the mean nadir of HBsAg was -51% (range -46 to -59) with a mean change on day 85 of -22% (range -7 to -40). For cohort 2, the percent reduction in HBsAg was statistically significant versus placebo (p < 0.05) for days 3 through 43 post-dose. For cohort 2, the mean day of HBsAg nadir was day 33 with a range of day 8 to day 57.

Arrowhead believes that this is the first time that a reduction in HBsAg mediated through RNA interference has been demonstrated in patients with chronic HBV infection. This study is ongoing with follow up continuing on Cohort 3 (3.0 mg/kg) and recruitment underway for a fourth cohort of patients at 4.0 mg/kg.

Preparations are underway to initiate a series of multi-dose Phase 2b studies of ARC-520, for which the Company plans to file with regulatory authorities in the fourth quarter of 2014. These studies are planned to have clinical sites in the US, Western Europe, Asia, and potentially other countries and/or regions. Several studies are currently contemplated, including ARC-520 in combination with entecavir or tenofovir as well as combination studies that add an immunostimulatory agent.

ARC-AAT Data

Arrowhead also presented data on ARC-AAT, its clinical candidate for the treatment of liver disease associated with Alpha-1 Antitrypsin Deficiency (AATD), a rare genetic disease that severely damages the liver and lungs of affected individuals. These patients synthesize a mutant form of AAT (Z-AAT) in the liver which is poorly secreted and accumulates, resulting in liver injury. The goal of treatment with ARC-AAT is to silence production of Z-AAT thereby preventing further accumulation of Z-AAT in the liver and potentially reversing pre-existing liver injury and fibrosis.

The presentation in the prestigious Plenary Session titled, “A hepatocyte-targeted RNAi-based treatment for liver disease associated with alpha-1 antitrypsin deficiency,” was presented by Christine Wooddell, Ph.D., Group Leader, Arrowhead Research. AASLD President Dr. Adrian Di Bisceglie, MD, FACP also highlighted the presentation, along with just ten others, in the President’s Press Conference as a program that holds great promise for patients.

In preclinical studies with PiZ mice, which are genetically modified to produce the mutant human AAT (Z-AAT), ARC-AAT induced a greater than 95 percent reduction in circulating AAT after a single dose with a long duration of effect. Area covered by Z-AAT globules and globule size within the liver were significantly reduced after a single dose of ARC-AAT at day 15 post-dose (p < 0.005) and day 29 post-dose (p < 0.01). Multi-dose studies in PiZ mice showed that ARC-AAT was effective at reducing and preventing Z-AAT aggregates in the liver. At week 13 of the study, after 4 biweekly doses, the ARC-AAT treated group show 99% less soluble (monomer) Z-AAT and 79% less insoluble (polymer) Z-AAT, normalized to a saline control group. Thus, injection of ARC-AAT in transgenic mice expressing human Z-AAT resulted in prevention and reduction of Z-AAT globules and, importantly, liver inflammation.

In primate studies, a 90% reduction of AAT in serum was observed after a single injection, which persisted for over ten weeks with greater than 80 percent knockdown observed at the six-week time point. Multi-dose studies in primates showed a sustained reduction of AAT with once every six weeks dosing, suggesting that once monthly or less frequent dosing may be sufficient to maintain approximately 80-90% knockdown in humans. The treated animals showed no changes in clinical chemistry (ALT, AST, BUN, Creatinine), indicating that ARC-AAT appeared to be well tolerated at these optimal therapeutic dose levels.

About ARC-520

Arrowhead’s RNAi-based candidate ARC-520 is designed to treat chronic HBV infection by reducing the expression and release of new viral particles and key viral proteins. The goal is to achieve a functional cure, which is an immune clearant state characterized by hepatitis B s-antigen negative serum with or without sero-conversion. The siRNAs in ARC-520 intervene at the mRNA level, upstream of where nucleotide and nucleoside analogues act. In transient and transgenic mouse models of HBV infection, a single co-injection of Arrowhead’s Dynamic Polyconjugate (DPC) delivery vehicle with cholesterol-conjugated siRNA targeting HBV sequences resulted in multi-log knockdown of HBV RNA, proteins and viral DNA with long duration of effect. Arrowhead has completed enrollment in a Phase 1 single ascending dose study in normal volunteers. The company is conducting a single dose Phase 2a study in chronic HBV patients, and expects to follow with multi-dose, multi-national Phase 2b studies. Approximately 350 million people worldwide are chronically infected with the hepatitis B virus. Chronic HBV infection can lead to cirrhosis of the liver and is responsible for 80% of primary liver cancers globally.

About ARC-AAT

Arrowhead has developed ARC-AAT for the treatment of liver disease associated with Alpha-1 Antitrypsin Deficiency (AATD), a rare genetic disease that severely damages the liver and lungs of affected individuals. ARC-AAT employs a novel unlocked nucleobase analog (UNA) containing RNAi trigger molecule designed for systemic delivery using the Dynamic Polyconjugate delivery system. ARC-AAT is highly effective at knocking down the Alpha-1 antitrypsin (AAT) gene transcript and reducing the hepatic production of the mutant AAT (Z-AAT) protein. Reduction of liver production of the inflammatory Z-AAT protein, which has been clearly defined as the cause of progressive liver disease in AATD patients, is important as it is expected to halt the progression of liver disease and potentially allow fibrotic tissue repair. The Company plans to file with regulatory authorities in the fourth quarter of 2014 and commence clinical studies shortly after receiving permission to begin.

About Arrowhead Research Corporation

Arrowhead Research Corporation is a biopharmaceutical company developing targeted RNAi therapeutics. The company is leveraging its proprietary Dynamic Polyconjugate delivery platform to develop targeted drugs based on the RNA interference mechanism that efficiently silences disease-causing genes. Arrowhead’s pipeline includes ARC-520 for chronic hepatitis B virus, ARC-AAT for liver disease associated with Alpha-1 antitrypsin deficiency, and partner-based programs in obesity and oncology.

For more information please visit http://www.arrowheadresearch.com, or follow us on Twitter @ArrowRes. To be added to the Company's email list and receive news directly, please visit http://ir.arrowheadresearch.com/alerts.cfm.

Source: Arrowhead Research Corporation

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Vince Anzalone, CFA
626-304-3400
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Value-based Medicine – The Liver Meeting® 2014

Published on Nov 9, 2014

AASLD TV was pleased to discuss this topic which perhaps doesn’t get enough attention. Moderators Mario Strazzabosco, MD, PhD and Guadalupe Garcia-Tsao, MD talk about the importance of returning the practice of hepatology to its appropriate focus: enabling health and effective care of patients with liver disease and how doing so can significantly impact the value of patient outcomes.

Source WebsEdgeHealth

Advances for Practitioners - New Treatments for Hepatitis C - The Liver Meeting® 2014

Published on Nov 9, 2014

New Treatments for Hepatitis C Moderator Hugo Rosen, MD, FACP talks to AASLD TV about this exciting session concerning current and emerging regimens for treatment of HCV as well as how to identify patients at risk of developing HCV-related hepatocellular carcinoma.

Source WebsEdgeHealth

Interim Data from Proof-of-Concept Study of Merck’s Investigational Hepatitis C Treatment Grazoprevir/Elbasvir in Combination with a Nucleotide Inhibitor (C-SWIFT study) Presented at The Liver Meeting®

Merck Plans to Initiate Phase 2 C-CREST Program to Evaluate Merck’s Triple Combination of Grazoprevir/Elbasvir with MK-3682 (formerly IDX21437), a Novel Nucleotide Inhibitor, in Q1 2015

Sunday, November 9, 2014 6:53 pm EST

BOSTON--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the presentation of interim data from the C-SWIFT study exploring the potential of a candidate triple-therapy regimen consisting of the fixed-dose combination of grazoprevir/elbasvir (MK-5172/MK-8742, MK-5172A), the company’s investigational NS3/4A protease inhibitor and NS5A inhibitor, in combination with sofosbuvir, a nucleotide (NS5B) inhibitor for the treatment of chronic hepatitis C virus (HCV) infection. Preliminary findings in treatment-naïve HCV genotype 1- (GT1) infected non-cirrhotic patients, following six and four weeks of treatment, and patients with cirrhotic disease, following eight and six weeks of treatment, will be presented by Dr. Eric Lawitz, vice president, scientific and research development, The Texas Liver Institute, San Antonio, TX and C-SWIFT lead investigator. This poster presentation is part of a late-breaking abstract session at the 65^th American Association for the Study of Liver Diseases (AASLD) Annual Meeting, also known as The Liver Meeting^®.

“These interim data provide a compelling proof-of-concept for the potential of an eight- or six-week triple therapy course in treatment-naive patients with genotype 1 disease, including cirrhotic patients,” said Dr. Lawitz. “These findings will inform the design of larger studies aimed at understanding the potential of short-duration triple therapy across multiple patient types.”

To date, the investigational triple therapy has shown response rates (sustained virologic response¹ [SVR] at 4/8 weeks following therapy) ranging from 80 percent to 94.7 percent in cirrhotic and non-cirrhotic patients following six and eight weeks of treatment in this study, as shown in table 1. The four-week regimen resulted in sub-optimal efficacy.

All 28 patients not achieving SVR4/8 relapsed following the end of therapy. Of these patients, 25 (89%) were genotype 1a (GT1a) and three (11%) were genotype 1b (GT1b) [82% of enrolled subjects were infected with HCV GT1a at baseline]. Sequence analysis of virologic failures is so far available for 23 patients. Wild type virus was determined to be the cause in 12 of the relapsed patients. In the other relapsed patients, 10 had elbasvir-resistant viral variants and one had a variant resistant to both grazoprevir and elbasvir.

In this study, the co-administration of grazoprevir/elbasvir and sofosbuvir was generally well-tolerated. The most common adverse events associated with the triple regimen were: headache (4%), fatigue (2%) and nausea (2%). One patient withdrew from the study for reasons unrelated to treatment.

“Our goal is to establish a simple, effective, well-tolerated regimen that is applicable across the diverse population of patients with HCV,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “The preliminary data provide us with the confidence to initiate our C-CREST study to evaluate a triple combination comprising Merck’s investigational candidates from three major therapeutic classes of HCV medicines.”

About C-SWIFT

The C-SWIFT study enrolled a total of 102 treatment-naïve patients with HCV genotype 1 (GT1a and GT1b) infection at The Texas Liver Institute, San Antonio, TX. Treatment-naïve, non-cirrhotic patients were randomized to receive the fixed-dose combination of grazoprevir/ elbasvir (one pill containing 100 mg, 50 mg respectively) plus the nucleotide inhibitor sofosbuvir (400 mg) once daily for eight, six or four weeks. Similarly, treatment-naïve, cirrhotic patients were randomized to receive the investigational combination for either eight or six weeks. The primary endpoint of the study is the percentage of patients achieving sustained virologic response 12 weeks after the completion of therapy (SVR12). An additional analysis of patients with genotype 3 (GT3) HCV enrolled in the C-SWIFT study will be presented at a future scientific congress.

About C-CREST

Based upon the interim findings from C-SWIFT and data from the Phase 1 clinical trial for MK-3682, also presented at The Liver Meeting^®, Merck plans to initiate Phase 2 clinical trials evaluating the efficacy and safety of two short-duration triple therapy regimens: MK-3682 in combination with grazoprevir/elbasvir; and MK-3682 in combination with grazoprevir and Merck’s investigational early-stage NS5A inhibitor MK-8408, in non-cirrhotic HCV patients. Part A of the Phase 2 studies is planned to evaluate eight weeks of therapy among non-cirrhotic HCV-infected patients, and Part B studies may evaluate shorter courses of treatment based on findings from Part A.

MK-3682 (formerly IDX21437) Data Presentation at AASLD Annual Meeting

MK-3682 is an investigational oral prodrug HCV nucleotide analogue NS5B polymerase inhibitor. Phase 1/2a clinical trial results for MK-3682 are scheduled to be presented in a poster session (Abstract #1974) at The Liver Meeting^®. HCV infected subjects (24 GT1 and 20 GT2/3) were randomized to receive placebo or 50, 150 or 300 mg of MK-3682 daily for seven days. Following initial pharmacokinetic and pharmacodynamic analysis, enrollment into the 50 mg and 150 mg treatment groups was discontinued due to a small reduction in viral load. In the 300 mg arms, the mean maximum viral load reductions from baseline for 7-day dosing were 4.6 and 4.1 log10 IU/mL in GT 2 (n=3) and GT 3 subjects (n=7), respectively. In GT1a (n=3) and GT1b subjects (n=5), the mean maximum viral load reductions from baseline for 7-day dosing were 4.8 and 3.9 log10 IU/mL respectively.

To date, no discontinuations due to an adverse event and no drug-related serious adverse events have been reported. Most adverse events were mild or moderate in intensity, with no apparent dose effect. There were no clinically significant abnormalities reported in routine blood and urine biomarker panels and physical examinations. Initial results from this study were previously announced by Idenix Pharmaceuticals in April 2014.

About Grazoprevir/Elbasvir

Grazoprevir/elbasvir (MK-5172/MK-8742, MK-5172A) is an investigational, oral, once-daily, fixed-dose combination chronic HCV treatment, consisting of grazoprevir, an investigational oral, once-daily HCV NS3/4A protease inhibitor, and elbasvir, an investigational oral, once-daily HCV NS5A replication complex inhibitor. In October 2013, Merck announced that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to grazoprevir/elbasvir for treatment of chronic HCV infection. Breakthrough therapy designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

Merck’s Commitment to HCV

For nearly 30 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver innovative healthcare solutions that support people living with HCV worldwide.

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies 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 healthcare legislation in the United States and internationally; global trends toward healthcare 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 2013 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).

¹ Defined as HCV RNA below the limit of quantification or below the limit of detection at the last visit on record – 4, 8, or 12 weeks after the completion of therapy.

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Justin Holko, 908-423-5088

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Transferring Liver Patients May Do More Harm Than Good

Published: Nov 9, 2014

By Ed Susman , Contributing Writer, MedPage Today

Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

BOSTON -- Patients with decompensated liver cirrhosis who were transferred from hospitals to a transplant center faced worse outcomes, researchers suggested here.

In a series of 99 patients transported from outlying hospitals to a liver transplant center, 10 were eligible for transplant, but only three of them underwent liver transplantation during their admission while seven others died, reported Chad Cornish, MD, of the University of Rochester in N.Y., and colleagues.

Cornish's group found that the mean length of stay at the outside hospital was 6.8 days, and the time of the request to transfer the patients and delivery of the patient to the tertiary care center took a mean of 1.2 days, according to their poster presentation at the America Association for the Study of Liver Diseases annual meeting.

Transfer delays were caused by lack of bed space at the tertiary center or because the patient was too unstable to transfer. However, Cornish said none of the patients in the single-center study experienced a transfer delay because of health insurance issues.

"These patients have underlying liver disease and they may decompensated due to encephalopathy -- change in mental status, a gastrointestinal bleed, ascites that are no longer under control. Anyone who is cirrhotic is a sick patient to begin with; they have some other insult and their condition tailspins from there," Cornish said.

"Sometimes we can stabilize them," he continued, "but sometimes the patient has spiraled so far out of control, there is little that can be accomplished. A lot of patients that are transferred to [the transplant center] -- mainly in hopes that a liver transplant would be possible -- do not do well."

Cornish and colleagues wanted to determine how well these transferred patients fared when sent to the tertiary facility.

"Tertiary care liver transplant centers frequently receive requests from outlying hospital to transfer patients with decompensated cirrhosis for a higher level of care, including evaluation for liver transplantation," they explained. "There have been no published studies looking at clinical outcomes for patients with acute decompensated cirrhosis who are transferred to a liver transplant center or barriers to the interhospital transfer."

The study population consisted of patients (ages 18 and up) transferred from an outlying hospital to the university's Strong Memorial Hospital (SMH) for management of acute decompensated cirrhosis between January 2011 and July 2013. They were identified through the hospital's transfer request logs.

Among 30 cases of interhospital transfer delay, 30% were due to lack of bed availability while 13% cases of delay were due to the patient being too unstable to transfer, the authors wrote.

Nearly one-third of the patients died during their initial admission after a mean length of stay while two additional patients died after being transferred on a separate occasion. Mean peak outside hospital Model for End-Stage Liver Disease (MELD) score for patients who died at SMH was 31.3.

His group concluded that "very few patients with acute decompensated cirrhosis transferred from an outlying hospital were suitable for liver transplantation and an even smaller number of patients were transplanted. A substantial number of patients died following a prolonged hospitalization. Given the limited resources and cost associated with transferring patients to a tertiary care liver transplant center, patient selection for transfer is crucial in order to provide optimal care and allocate researches appropriately."

They called for additional studies to identify risk factors that can help prioritize patient transfers.

In commenting of the presentation, Mohsen Hasanin, MD, from the University Alabama in Birmingham, told MedPage Today that "when we see patients from outside the hospital, they are pretty much gone. These patients need to be transferred earlier. By the time they are transferred from primary care or from the outpatient setting by gastroenterologists or hepatologists, they have very bad as outcomes as transplant."

Cornish and co-authors disclosed no relevant relationships with industry.

Hasanin disclosed no relevant relationships with industry.

Source

Treating All Patients with Hepatitis C Who Would Be Diagnosed by Age-based Screening Is Cost Effective

Presented: Monday, November 10, 2014, 3:15 pm Eastern - Hynes Convention Center, Boston, MA

BOSTON, Nov. 9, 2014 /PRNewswire/ -- The newest and most effective drugs for the treatment of hepatitis C have a cure rate of up to 98 percent, but the cost of these therapies has been controversial. Accurately assessing the cost of treating all patients with HCV in the US has yet to be determined.

Part of the problem is getting an accurate count of the Americans with HCV as those with HCV are often asymptomatic and many are undiagnosed. The Centers for Disease Control and Prevention (CDC) has recommended a one-time age-based screening of all baby boomers (those born between 1945 and 1965). Risk-based screening was the standard protocol before the CDC's recent recommendation.

Researchers used a decision analytic Markov modeling approach to estimate the cost-effectiveness of screening and treating patients with HCV. They created a model based on five strategies of treatment and simulated patients until death:

1. Risk-based screening and treating all patients with HCV
2. Age-based screening and treating all patients with HCV
3. Risk-based screening and treating patients based on liver disease stage
4. Age-based screening and treating patients based on liver disease stage
5. No screening and no treatment

They assumed treatment for fibrosis stages F2 to F4, a 98 percent cure rate, and the cost of the drugs at current prices. They assumed 1.2-1.4 million new patients would be diagnosed with HCV from age-based screening. Treatment effectiveness was measured in quality-adjusted life years, which assumes that patients with HCV would live their lives without HCV progressing to cirrhosis, decompensated liver disease, or liver transplantation. Different screening and treatment strategies were compared to each other based on the standard threshold for cost-effectiveness (incremental cost-effectiveness ratio or ICER) from a societal perspective.

The authors concluded that birth cohort screening followed by treating all HCV (+) patients was the most cost-effective strategy with ICERs well below the accepted threshold of $50,000 per quality adjusted years of life gained. The lead investigator, Zobair Younossi MD, MPH, FAASLD concluded that "screening and treating baby boomers with highly effective and well tolerated all oral anti-HCV regimens are highly cost-effective with great health and economic benefits at the population level." Dr. Younossi is Chairman of Medicine, Inova Fairfax Medical Campus and Vice President for Research, Inova Health system, Falls Church, Virginia.

Abstract title:

The use of all oral regimens for treatment of chronic hepatitis C (CHC) coupled with birth cohort screening is highly cost effective: The health and economic impact on the US population.

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 Boston, November 7-11, will bring together more than 9,000 researchers from 55 countries.

A pressroom will be available from November 7 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.

Media Contact: Gregory Bologna
703-299-9766
gbologna@aasld.org
Press Room: November 7 – 11, 2014
Hynes Convention Center, Boston, MA
Telephone: 617-954-2977

Researcher: Zobair Younossi, MD
Email: zobair.younossi@inova.org

This release was issued through The Xpress Press News Service, merging e-mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit http://www.XpressPress.com.

SOURCE American Association for the Study of Liver Diseases (AASLD)

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http://www.aasld.org

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Transplanting Patients with HIV and Liver Cancer

Attention: Medical & Science Editors/Producers

Media Contact: Gregory Bologna
703-299-9766
gbologna@aasld.org
Press Room: November 7 – 11, 2014
Hynes Convention Center, Boston, MA
Telephone: 617-954-2977

Researcher: Heather Platt, MD
Email: hplatt@gmail.com
Phone: 732-485-9222 

For Immediate Release
Presented: Date Monday, November 10

Liver transplantation is a therapeutic option for selected patients with liver cancer with high 5-year survival rates of 75 – 80 percent. HIV-infected patients often do not have access to liver transplantation, and experience with HIV-infected patients with liver cancer undergoing liver transplantation is limited.

An international group of researchers at 43 centers in North and South America, Europe, and Australia retrospectively identified 135 HIV-positive patients with hepatocellular carcinoma (HCC) who underwent potentially curative treatment.  Twenty-seven patients who underwent orthotopic liver transplantation (OLT) were compared to 108 patients who underwent either radiofrequency ablation, surgical resection, or percutaneous ethanol injection.

Compared to the 108 patients undergoing other potentially curative therapy, the 27 patients undergoing OLT were younger, had higher Child-Turcotte-Pugh scores (used to assess liver function), and more often had multiple liver tumors, but were otherwise similar in disease etiology, frequency of alcohol abuse, and control of HIV infection.

Patients who had a liver transplantation had a significantly higher 5-year survival rate of 85 percent, compared to 52 percent for all other curative therapies combined. The 5-year survival rate of 85 percent was similar to 75 – 80 percent reported in HIV-negative patients with HCC undergoing OLT.

When asked about the results, Heather Platt, MD, principal investigator of the study said, "The primary point of this study is to show that HIV+ patients with HCC should be included in evaluation for OLT, as there does not seem to be any difference in survival when compared to HIV negative patients. Importantly, the survival data, while retrospective, does indicate a benefit compared to other curative interventions. "

Dr. Platt also addressed barriers to transplanting these patients. Dr. Platt said, "The main barriers include a center's experience and comfort with transplanting HIV+ patients. HIV+ patients are examined quite carefully for compliance and for anticipation of post-transplant complications. This requires a comprehensive, multidisciplinary transplant program including specialists in HIV care."

Abstract title:
Liver transplantation for HIV-infected patients with hepatocellular carcinoma (HCC)

###

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 7-11, will bring together more than 9,000 researchers from 55 countries.

A pressroom will be available from November 7 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.

Source

Finding Hepatitis C in High-Risk Populations: How New York City Did It

Attention: Medical & Science Editors/Producers

Media Contact: Gregory Bologna
703-299-9766
gbologna@aasld.org
Press Room: November 7 – 11, 2014
Hynes Convention Center, Boston, MA
Telephone: 617-954-2977

Researcher: Mary Ford, MS
Email: mford4@health.nyc.gov
Phone: 347-396-2419

For Immediate Release
Presented: Monday, November 10 2014

It is estimated that 2.4 percent of New York City (NYC) residents have HCV infection, but half do not know their status. To address this gap, the NYC Department of Health and Mental Hygiene launched the Check Hep C Program, which, in its first year, helped increase the rate of complete hepatitis C (HCV) diagnostic testing among at risk populations and has successfully linked more people to HCV supportive services, care, and treatment.

The Check Hep C program funded eight organizations at 12 community sites, including syringe exchange programs and community health centers. Over 4,500 people were screened and tested, and of those who tested HCV RNA positive, 85 percent attended their first medical appointment and 50 percent remained in care, which put them in the position to benefit from the HCV treatment advances of 2014. In describing the Check Hep C program, Mary Ford, MS, program evaluator for the program said, "The screening protocol for the Check Hep C program includes testing those in the birth cohort as well as those who are at high risk from injection drug use either currently or in the past."

After Centers for Disease Control and Prevention (CDC) recommended a one-time screening for HCV infection for all Americans born from 1945 to 1965 (baby boomers), New York State passed a law mandating that health care providers offer a HCV test to individuals in this age group, and provide care or linkage to care for those who test positive. However, many people at high risk for HCV were not visiting a health care provider to get tested or screened.

According to Ms. Ford, "While a formal evaluation of the mandate has not been completed as of yet, we have collected anecdotal evidence from many of our partners and from providers that we have met with during the year, finding that adherence varies widely -- lack of knowledge by primary care providers, lack of accountability by leadership, lack of adequate resources for testing, lack of integration between service delivery locations, etc."

In order to increase screening in groups at highest risk for HCV, the Program generated awareness about HCV and recruited patients through a local media campaign and targeted outreach. The program improved rates of complete diagnosis through field based rapid testing, and confirmation (RNA testing) immediately after HCV antibody positive tests.

In the Check Hep C program population, the estimated prevalence of HCV infection was 14 percent, and 9 percent among persons born after 1965 and 14 percent among baby boomers. Among enrollees, 25 percent had injected drugs in the past (20 times more likely to have HCV infection), 15 percent were homeless (1.6 times more likely to have HCV infection), and 18 percent had been previously incarcerated (5 times more likely to have HCV infection). In addition to supporting the birth cohort based screening recommendation of the CDC, the authors of the article recommend expanding the Check Hep C model to settings with high-risk populations.

"Further outreach and education to primary care providers will be needed to fully implement the testing mandate, and programs like Check Hep C will play an integral role this process in high-risk communities, said Ms. Ford. "The successful model demonstrated in Check Hep C can be replicated not only in community-based organizations, but also in community health centers, and outpatient clinics of large medical centers."
Abstract title:
Check Hep C: A community-based approach to hepatitis C diagnosis in high-risk populations

###

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 Boston, November 7-11, will bring together more than 9,000 researchers from 55 countries.

A pressroom will be available from November 7 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.

Source

Combination therapy offers quicker, less toxic eradication of hep C in liver transplant patients

PUBLIC RELEASE DATE: 9-Nov-2014

Contact: Paul Scotti
scotti.paul@mayo.edu
904-953-0199
Mayo Clinic

JACKSONVILLE, Fla. -- All patients with hepatitis C who receive a liver transplant will eventually infect their new livers. These transplanted organs then require anti-viral treatment before they become severely damaged. But traditional post-transplant hepatitis C therapy can take up to a year, is potentially toxic and can lead to organ rejection.

Now, at the American Association for the Study of Liver Diseases (The Liver Meeting® 2014) in Boston, researchers at Mayo Clinic report that use of two new oral medications post-transplant is safe and beneficial, and requires only 12 weeks of treatment.

"This is the first study to examine the use of these two new drugs -- simeprevir and sofosbuvir -- in liver transplant recipients, and, based on this large study, we find it to be a better option than current treatment," says the study's lead researcher, Surakit Pungpapong, M.D., a transplant hepatologist and an associate professor of medicine at Mayo Clinic in Florida.

Standard pre- and post-transplant treatment requires the use of interferon injections, along with ribavirin. Interferon engages the human immune system to fight the hepatitis C virus, but this immune response can also lead to organ rejection, Dr. Pungpapong says. Interferon can cause a variety of side effects, including anemia, depression, irritability, flu symptoms, insomnia, and hair loss, among others, he says.

Given the clinical importance of the study, results are being presented at the meeting in a plenary session.

Chronic hepatitis C virus is the most common chronic bloodborne infection in the United States, affecting more than 3 million individuals. Most infected people have no symptoms of the disease until liver damage from chronic inflammation occurs decades later -- which happens to 5-30 percent of infected individuals. Hepatitis C infection accounts for two-thirds of newly diagnosed chronic liver disease cases and 40 percent of liver transplants.

For this study, Mayo Clinic researchers enrolled post-transplant patients at their three sites, including Rochester, Minnesota, Scottsdale, Arizona and the Mayo Clinic Transplant Center in Jacksonville, Florida, which has one of the five most active liver transplants programs nationwide. Researchers will report on outcomes of more than 100 patients, but the study is still ongoing.

These patients were too sick to be treated for hepatitis C before their transplant, says Dr. Pungpapong. "By the time liver cirrhosis occurs, it could be too late to use anti-viral drugs," he says.

Simeprevir and sofosbuvir were approved for pretransplant use last year by the Food and Drug Administration (FDA), but not as a combined therapy. The FDA also required that they be combined with interferon and ribavirin.

But in a large clinical trial, researchers tested simeprevir and sofosbuvir without interferon -- an off-label use -- in pretransplantation patients and found the combination to be a brief and effective therapy. In this study, the Mayo researchers extended the idea of using these drugs together without interferon in post-transplantation patients.

The researchers found that eradication of the virus in the patients was excellent -- more effective than the use of interferon and ribavirin -- and with much fewer side effects. "We believe use of these drugs, both pre- and post-transplant represents a substantial clinical advance," Dr. Pungpapong says.

###

The study was funded in part by a Davenport grant from the Department of Transplant of Mayo Clinic in Jacksonville, Florida.

About Mayo Clinic

Recognizing 150 years of serving humanity in 2014, Mayo Clinic is a nonprofit worldwide leader in medical care, research and education for people from all walks of life. For more information, visit 150years.mayoclinic.org, MayoClinic.org or newsnetwork.mayoclinic.org.

MEDIA CONTACT: Paul Scotti, Mayo Clinic Public Affairs, 904-953-0199. Email: scotti.paul@mayo.edu

Source

After hepatitis C cure, companies target next big liver disease market

By Bill Berkrot

NEW YORK Sun Nov 9, 2014 6:37pm IST

(Reuters) - Now that new medicines promise to cure millions of hepatitis C patients in coming years, drugmakers including Gilead Sciences Inc are turning their attention to other liver diseases, with a potential market that could rival the success of statins, which generated more than $30 billion a year in sales at their peak.

Several companies are working on treatments for hepatitis B, which can be controlled but not yet cured, and for fatty liver conditions caused by rising obesity, which without treatment could affect half of all Americans by 2030, according to the American Liver Foundation (ALF). Some of the drugs will address advanced fibrosis and cirrhosis, which are the scarring that virtually all liver diseases cause without effective treatments. Each of these drugs, once approved, could reach annual sales of as much as $10 billion, industry analysts said.

   Most of the treatments are now in early Phase I or Phase II clinical trials, with more informative interim data on several expected over the course of the next year.

Gilead, which was first to market with its hepatitis C cure Sovaldi late last year and has been racking up about $3 billion in sales each quarter, is a solid bet to be among the leaders in the next wave of liver therapies, experts said.

"The Gilead program is encouraging," said Dr. Naga Chalasani, director of gastroenterology and hepatology at Indiana University Hospital in Indianapolis, who is participating in clinical trials of promising drugs from Gilead and others.

Drugmakers are working to address the fatty liver disease known as NASH, or nonalcoholic steatohepatitis. Without treatment, NASH can progress to liver-destroying cirrhosis and potentially cancer.

ALF estimates that non-alcoholic fatty liver disease, including NASH, affects up to 30 percent of people in the United States. It can be caused by bad diets and alcohol abuse, and has also been tied to diabetes.

"We have no treatment for that condition other than tell a patient they need to lose weight," said Dr. Mauricio Lisker-Melman, director of the hepatology program at Washington University School of Medicine in St Louis.

   Intercept Pharmaceuticals has attracted the most attention. Just released final data from a mid-stage clinical trial showed its obeticholic acid halted NASH progression and improved liver scarring in primarily moderately ill patients. "For now, no one else has demonstrated an antifibrotic effect in this population, and I believe we are ahead of the pack in that sense," said Intercept Chief Executive Mark Pruzanski.

Intercept plans to begin a Phase III trial with at least 1,000 more seriously ill patients next year.

Dr. Scott Friedman, dean for therapeutic discovery at Mt. Sinai Hospital in New York, who has worked with virtually all the companies in the field, said most were first testing drugs in patients whose liver damage is not advanced.

"Gilead has sort of leapfrogged that," Friedman said, tackling more serious damage, as its simtuzumab targets fibrotic scarring directly, rather than inflammation or other drivers of disease. Reversing cirrhosis and improving liver function is "the highest bar I can think of in this business, and it would be spectacular," he said.

    Gilead faces competition from several smaller companies with promising drugs in development, including Intercept, France's Genfit, Israel's Galmed, Galectin Therapeutics, Conatus Pharmaceuticals and Raptor Pharmaceuticals, specialists said.

    Gilead's antibody simtuzumab blocks an enzyme called LOXL2 that is directly involved in laying down bands of collagen that form the scar tissue behind cirrhosis. The collagen bands, which result from a wide variety of assaults on the liver, including alcohol and drug abuse, cross link haphazardly to destroy the liver's architecture and function.

Gilead expects to have a strong indication of whether its drug is working when one-year data from a two-year Phase II study becomes available next year.

"We have a very active research program," said Mani Subramanian, head of liver disease clinical research at Gilead. "We're targeting everything: metabolic issues, inflammation and fibrosis directly." He acknowledged challenges faced by drugmakers trying to address more advanced liver disease: "It's been a graveyard for drugs that try to reverse fibrosis," Subramanian said.

    NOT FOR FAINT OF HEART

    Chalasani at Indiana University Hospital estimated there may be 20 different drugs being tried by various drug companies that seem to be good targets.

But betting on them is not for the faint of heart. Intercept's shares shot from about $72 to over $400 in a matter of days in January after it was announced the trial of its drug would meet the intended goal. On the flip side, Galectin lost nearly two thirds of its value in July, when its NASH drug using a different approach had a setback in a Phase I trial.

    Conatus is first testing its drug, emricasan, in patients facing acute liver failure, which has a 50 percent mortality rate in 28 days. Chief Executive Steven Mento said the goal was to "rescue these patients and prevent catastrophic organ failure." The company plans to work its way back, testing on less severely ill patients. The drug targets inflammation and excessive cell death seen as drivers of the disease.

    Dr. David Bernstein, chief of hepatology at North Shore University Hospital in Manhasset, N.Y., called the Conatus drug exciting and the initial trial a sensible approach.

    "There's limited downside because there's nothing else that can be done anyway," said Bernstein, who expects to be involved in future emricasan trials. "If you can reverse cirrhosis, you really will change the impact of liver disease worldwide."

Drugs that succeed in reversing cirrhosis "can be as big a class as the class of statins," said Conatus's Mento, referring to cholesterol drugs, such as Pfizer's Lipitor, which alone at its peak had annual sales of about $13 billion.

    Raptor, by contrast, is developing a drug for NASH in children, a growing problem that has left liver specialists fearing an obese generation that could require liver transplants in the prime of life.

    Raptor is testing a drug already approved for use in children for an extremely rare kidney disease. "In terms of safety, it's well established," said Raptor President and CEO designate Julie Anne Smith. It is now engaged in a year-long mid-stage trial of 169 children whose NASH was confirmed by liver biopsy with data expected in the first half of next year.

    Companies are waiting for the U.S. Food and Drug Administration to outline what it will take to approve a NASH drug. "The FDA is struggling with what constitutes a meaningful improvement with a patient," Gilead's Subramanian said.

Goals such as reducing fat buildup or modestly improving fibrosis would likely be simpler and quicker to achieve, for example, than avoiding need for liver transplants.

    The FDA is working "to identify clinically meaningful endpoints for NASH and related liver diseases to help guide drug development," it said in a statement.

The uncertainty from the FDA also creates risks for investors and has led some analysts to focus on other liver therapies. RBC Capital Markets analyst Michael Yee favors companies taking on hepatitis B, such as Arrowhead Research Corp, Canada's Tekmira Pharmaceuticals, Gilead and Isis Pharmaceuticals in partnership with GlaxoSmithKline. And one private company not to be ignored, OnCore Biopharma, founded by former Pharmasset executives, including the inventor of Gilead's Sovaldi.

    While finding a cure for hepatitis B will not be easy, trials would mirror those for hepatitis C, with a simple blood test yielding clear results in months rather than years.

(Reporting by Bill Berkrot. Editing by Michele Gershberg and John Pickering)

Source

AASLD 2014:"It's a Remarkable Time:" Hepatitis C Special Interest Group 2014 Symposium

Published on Nov 8, 2014

Moderator Michael W. Fried, MD outlines the topics presented at this year's AASLD Hepatitis C Special Interest Group program, including access to medication and unique populations that have been difficult to treat.

Source AASLDVideo

What Does Social Media and Crowdsourcing Have to Do With Women and Liver Disease?

Presented: Sunday, November 9, 2014, 4:00 pm Eastern - Hynes Convention Center, Boston, MA

BOSTON, Nov. 8, 2014 /PRNewswire/ -- Autoimmune hepatitis is a chronic liver disease that is found more frequently in women than men. Researchers at Indiana University studied the environmental exposures possibly related to autoimmune hepatitis and reported their findings at the annual meeting of the American Association for the Study of Liver Diseases. "Interestingly, autoimmune hepatitis is quite far behind other autoimmune liver diseases in terms of environmental risk assessment," said Craig Lammert, MD, principal investigator on the study.

In addition to assessing the environmental exposures, the research team used social media and Amazon Mechanical Turk to conduct two independent surveys. "Social media in clinical research is an evolving field. We have only just started to tap into the diverse application of this platform and clinical studies," said Dr. Lammert, "It will grow, and, I suspect, it will change some of the ways we conduct future studies."

Seven autoimmune hepatitis social media groups -- referred to in the study as cases -- were identified. Amazon Mechanical Turk is a crowdsourcing website used to connect work requesters with a freelance workforce, and this system was used to identify healthy participants for the control group.

Using this system, 430 dietary (152 cases from the social media groups/278 controls from Amazon Mechanical Turk) and 390 tobacco surveys (164 cases from the social media groups/ 226 controls from Amazon Mechanical Turk) were completed over one month and returned for statistical analysis.

There was no difference in coffee consumption, other aspects of diet, or smoking with the exception that those in the control group were more likely to be current smokers. However, a significantly lower number of cases reported breast feeding as infants than those in the control group -- 49 percent compared with 65 percent. According to Dr. Lammert, "This is the first time we have seen this inverse association with breast feeding and autoimmune hepatitis. We became interested in this idea, as there have been similar associations reported in the literature for other autoimmune diseases -- but none associated with the liver."

The study demonstrates two distinctly different facts -- the feasibility of using social media for conducting such research and the relationship between breastfeeding and autoimmune hepatitis. "Social media is an amazing tool, our group has and will continue to utilize it to study autoimmune hepatitis," said Dr. Lammert, "but we have learned that these studies must be completed carefully. A limitation is the challenge of patient-reported disease and data; however, we believe with structured and listed inclusion and exclusion criteria, we can adequately conduct epidemiologic research in this manner."

Dr. Lammert concluded by saying, "There have not been sizeable or high-quality studies examining the environmental exposure risks in autoimmune hepatitis. We plan to conduct follow-up studies to attempt to replicate this finding but also dissect the mechanism for the observed effect."

Abstract title:
A preliminary study utilizing social media and crowdsourcing shows an inverse relationship between breast feeding as an infant and the presence of autoimmune hepatitis

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 Boston, November 7-11, will bring together more than 9,000 researchers from 55 countries.

A pressroom will be available from November 7 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.

Media Contact: Gregory Bologna
703-299-9766
gbologna@aasld.org
Press Room: November 7 – 11, 2014
Hynes Convention Center, Boston, MA
Telephone: 617-954-2977

Researcher: Craig Lammert, MD
Email: clammert@iu.edu
Phone: 317-201-5740

This release was issued through The Xpress Press News Service, merging e-mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit http://www.XpressPress.com.

SOURCE American Association for the Study of Liver Diseases

RELATED LINKS
http://www.aasld.org

Source

Intercept Announces Additional Data for OCA in Primary Biliary Cirrhosis

New Analyses of Data From POISE -- the First Phase 3 Trial in PBC in Two Decades -- Examine the Efficacy, Safety and Tolerability Profile of OCA

NEW YORK, Nov. 8, 2014 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT) (Intercept), a clinical stage biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat chronic liver and intestinal diseases, announced today new analyses of data from clinical trials on obeticholic acid (OCA) in patients with primary biliary cirrhosis (PBC). Six posters, including posters with new analyses of data from POISE – the first Phase 3 trial in PBC in two decades – are being presented at today's poster session at the American Association for the Study of Liver Disease (AASLD) Annual Meeting.

OCA, Intercept's lead product candidate, is a bile acid analog and first-in-class agonist of the farnesoid X receptor (FXR) in development for PBC, nonalcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC) and other chronic liver diseases.

In March 2014, Intercept announced that OCA met the primary endpoint of the POISE trial with high statistical significance (p < 0.0001). The posters to be presented at AASLD provide the following information relating to OCA in PBC:

• Poster 318 provides new subgroup analyses of the treatment effect for OCA across a range of patient characteristics associated with greater risk of adverse clinical outcomes, including age at diagnosis, duration of PBC and baseline alkaline phosphatase (ALP).
• Poster 295 presents analyses on the effects of OCA treatment versus placebo on markers of cholestasis (ALP, bilirubin) and hepatobiliary damage (GGT, AST, and ALT), as well as markers of inflammation (C-reactive protein or CRP) and apoptosis (cytokeratin-18 or CK-18).
• Poster 309 presents POISE results in relation to the proportion of patients achieving a response defined by different response criteria, other than the POISE endpoint, such as Paris I, Paris II and Rotterdam.
• Posters 305 and 310 cover new information relating to the titration arm of POISE, where approximately half the patients in the titration arm had their OCA dose increased from 5 mg to 10 mg after six months of treatment based on clinical response. These posters present new data regarding the potential utility of titration as a dosing strategy in the context of managing pruritus, the primary tolerability issue of OCA treatment, while investigating the effects of titration on the efficacy of OCA treatment.
• Poster 319 describes the long-term safety and efficacy results from open-label treatment of OCA for over four years as part of the long-term safety extension trial on patients who participated in a Phase 2 PBC trial that evaluated OCA monotherapy.

Linie Moore, President of the PBCers patient advocacy group, commented on the new PBC research being presented at AASLD: "In the time since I was first diagnosed with PBC almost 20 years ago, there have been no new medications introduced to treat my disease, so it is both gratifying and exciting to see so much progress being made with OCA as a potential new PBC therapy. We hope the PBC community's efforts to encourage research and awareness will continue to inspire new advances in the years to come."

About POISE

The POISE trial studied the safety and efficacy of a once-daily treatment with OCA in PBC patients with an inadequate therapeutic response to, or who are unable to tolerate, ursodiol. The primary endpoint of the 12-month double-blind portion of the trial, completed in March 2014, was the achievement of both an ALP level < 1.67x ULN with a ≥ 15% reduction from baseline and a normal bilirubin level, as compared to placebo. Patients with ALP and bilirubin levels below these thresholds have been shown in long-term clinical studies to have a significantly lower risk of progressing to liver transplant and death. There were 217 patients randomized to one of three groups in the trial: placebo, 10 mg OCA, or 5 mg OCA for six months titrated to 10 mg OCA based on clinical response; 216 patients were dosed.

Patients completing the double-blind phase had the option to continue in an open-label, long-term safety extension (LTSE) phase for another five years, during which all patients receive OCA treatment with daily doses starting at 5 mg and potentially titrating up to 25 mg a day, as clinically indicated. Of the 198 patients who completed the double-blind phase, more than 95% continued in the LTSE phase of the trial.

Additional information regarding the POISE trial can be found on the NIH clinical study listing web site: http://clinicaltrials.gov/ct2/show/NCT01473524.

About Primary Biliary Cirrhosis

PBC is an autoimmune liver disease that may progress to cirrhosis and liver failure, and it is currently the second leading indication for liver transplant among women in the United States. It is primarily a disease of women, afflicting approximately one in 1,000 women over the age of 40. Ursodiol is the only approved drug treatment for PBC and studies have shown that up to 50% of PBC patients may have an inadequate response, thereby remaining at risk of adverse outcomes.

About Intercept

Intercept is a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat orphan and more prevalent chronic liver and intestinal diseases utilizing its expertise in bile acid chemistry. The company's lead product candidate, obeticholic acid (OCA), is a bile acid analog and first-in-class agonist of the farnesoid X receptor (FXR). OCA is being developed for a variety of chronic liver diseases including primary biliary cirrhosis (PBC), nonalcoholic steatohepatitis (NASH), and primary sclerosing cholangitis (PSC). OCA has received Fast Track Designation in the United States and orphan drug designation in both the United States and Europe for the treatment of PBC and PSC. Several large, randomized, controlled studies of OCA in the treatment of chronic liver disease have been completed. These include Intercept's Phase 3 POISE trial for the treatment of patients with PBC and the FLINT trial for the treatment of patients with NASH. Intercept owns worldwide rights to OCA outside of Japan, China and Korea, where it has out-licensed the product candidate to Sumitomo Dainippon Pharma. For more information about Intercept, please visit the company's website at: www.interceptpharma.com.

Safe Harbor Statements

This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the utility of the selected endpoint for POISE or the other clinical data presented at AASLD; the acceptance by regulatory authorities of the POISE trial endpoint or results; the anticipated results of our clinical trials and other development activities; and our strategic directives under the caption "About Intercept." These "forward-looking statements" are based on management's current expectations of future events and are subject to a number of important risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: the initiation, cost, timing, progress and results of our development activities, preclinical studies and clinical trials; the timing of and our ability to obtain and maintain regulatory approval of OCA, INT-767, INT-777 and any other product candidates we may develop, particularly the possibility that regulatory authorities may require clinical outcomes data (and not just results based on achievement of a surrogate endpoint) as a condition to any marketing approval for OCA, and any related restrictions, limitations, and/or warnings in the label of any approved product candidates; our plans to research, develop and commercialize our product candidates; the election by our collaborators to pursue research, development and commercialization activities; our ability to attract collaborators with development, regulatory and commercialization expertise; our ability to obtain and maintain intellectual property protection for its product candidates; our ability to successfully commercialize our product candidates; the size and growth of the markets for our product candidates and our ability to serve those markets; the rate and degree of market acceptance of any future products; the success of competing drugs that are or become available; regulatory developments in the United States and other countries; the performance of third-party suppliers and manufacturers; our need for and ability to obtain additional financing; our estimates regarding expenses, future revenues and capital requirements and the accuracy thereof; our ability to retain key scientific or management personnel; and other factors discussed under the heading "Risk Factors" contained in our annual report on Form 10-K for the year ended December 31, 2013 filed on March 14, 2014 as well as any updates to these risk factors filed from time to time in our other filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Intercept undertakes no duty to update this information unless required by law.

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Are US Veterans Being Appropriately Tested and Treated for Hepatitis B?

Presented: Sunday, November 9, 2014, 5:00 pm Eastern - Hynes Convention Center, Boston, MA

BOSTON, Nov. 8, 2014 /PRNewswire/ -- Attendees of the annual meeting of the American Association for the Study of Liver Diseases (AASLD) listened to the results of a study on the adherence to its practice guidelines on testing for hepatitis B virus (HBV). Drs. Marina Serper, Kimberly Forde, and David E. Kaplan, of the University of Pennsylvania and Philadelphia VA Medical Center, examined the VA's Corporate Data Warehouse and concluded that the rates of serologic testing for HBV conducted by the VA were suboptimal as recommended by the AASLD practice guideline.

"While other chronic viral infections such as hepatitis C and HIV have received tremendous educational efforts," said Dr. Kaplan, principal investigator for the study, "hepatitis B has received far less attention, particularly outside communities with high numbers of immigrants from endemic regions."

Although only 1.0 percent (26,727) Veterans tested positive for hepatitis B, the study revealed that HBV infection is twice as common in the Veteran population as in the general population of the country.

Hepatitis B Surface Antigen (HBsAg) is the first test for detecting hepatitis B, but a positive result requires additional testing according to the AASLD practice guidelines on hepatitis B. Of the more than 2.5 million Veterans who had the HBsAg test, Dr. Serper's study identified 26,727 Veterans who tested positively. Of that group, the follow-up tests recommended by AASLD were not performed as frequently as recommended. In addition, those who were further tested received antiviral therapy only 25 percent of the time.

"Overall, 25 percent of individuals received antiviral therapy. Of those individuals that we can determine ought to be treated based on HBeAg, ALT, and HBV DNA criteria, only about 60 percent of individuals for whom treatment would likely be appropriate actually receive treatment. Individuals referred to a specialist were significantly more likely to receive treatment. Given low referral rates, these data are not surprising," said Dr. Kaplan.

Dr. Kaplan was asked to speculate about practice guideline adherence in the US population based on what's happening at the VA, and he said, "We suspect that in the baby boomer population there is a significant population of injection drug use-related chronic HBV that is undiagnosed and will not be captured by current USPSTF screening guidelines. Not only is there under-diagnosis, the majority -- up to 70 percent -- of screening HBsAg tests are not followed by referral from primary care to GI or ID providers with expertise in treatment decisions."

The study concluded that follow-up serologic testing for those who tested positive for HBV Surface Antigen and adherence to antiviral treatment recommendations was low, suggesting that provider education and improvements in clinical processes are needed to test and treat Veterans for hepatitis B.

When asked to address the need for testing, Dr. Kaplan said, "Appropriate serological testing is critical for determining whether or not an individual patient meets AASLD treatment criteria for HBV." Dr. Kaplan also addressed the importance of access to antiviral therapy, "Our and other data definitively demonstrate that antiviral therapy in appropriate individuals has a significant impact on mortality, hepatic decompensation, and HCC development. Improving adherence with guidelines is likely therefore to reduce death and healthcare costs," concluded Dr. Kaplan.

Abstract title:
Serologic testing rates among US veterans with hepatitis B

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 Boston, November 7-11, will bring together more than 9,000 researchers from 55 countries.

A pressroom will be available from November 7 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.

Media Contact: Gregory Bologna
703-299-9766
gbologna@aasld.org
Press Room: November 7 – 11, 2014
Hynes Convention Center, Boston, MA
Telephone: 617-954-2977

Researcher: Marina Serper, MD MS
Email: marina.serper@uphs.upenn.edu
Phone: 215-823-5800 x7401 

This release was issued through The Xpress Press News Service, merging e-mail and satellite distribution technologies to reach business analysts and media outlets worldwide. For more information, visit http://www.XpressPress.com."

SOURCE American Association for the Study of Liver Diseases

RELATED LINKS
http://www.aasld.org

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Phase 3 UNITY Trials Demonstrate High Cure Rates for Investigational, All-Oral Daclatasvir TRIO Fixed-Dose Combination in Genotype 1 Hepatitis C Patients, Including Those with Cirrhosis

Daclatasvir TRIO achieves 98% cure rate in treatment-naïve and 93% cure rate in treatment-experienced genotype 1 patients with cirrhosis when used with ribavirin, as shown in UNITY 2

12-week, all-oral treatment halves current regimen duration for hard-to-manage treatment-experienced genotype 1 patients with cirrhosis

Fixed-dose regimen also demonstrates 91% SVR rates in non-cirrhotic genotype 1 patients without requiring use of ribavirin

"Even with the most recent HCV treatment advances, genotype 1 patients with cirrhosis remain difficult to treat"

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced late-breaking data from the UNITY Trial program investigating a 12-week regimen of its all-oral daclatasvir (DCV) TRIO regimen – a fixed-dose combination of daclatasvir with asunaprevir (ASV) and beclabuvir (BCV) – in a broad range of patients with genotype 1 hepatitis C virus (HCV). The data will be presented at The Liver Meeting^® 2014, the Annual Meeting of The American Association for the Study of Liver Diseases (AASLD), in Boston, MA, November 7 – 11. The primary endpoint for both studies was the percentage of patients who achieved cure, defined as HCV RNA<LLOQ TD/TND at post-treatment week 12 for treatment-naïve and treatment-experienced patients.

The UNITY-2 study, which evaluated cirrhotic patients in a 12-week regimen of the DCV-TRIO, showed sustained virologic response 12 weeks after treatment (SVR12) among 98% of treatment-naïve and 93% of treatment-experienced cirrhotic patients with ribavirin (RBV) and 93% of treatment-naïve and 87% of treatment-experienced cirrhotic patients without ribavirin.

“Even with the most recent HCV treatment advances, genotype 1 patients with cirrhosis remain difficult to treat,” said Andrew J. Muir, M.D., MHS, Associate Professor of Medicine; Clinical Director, Gastroenterology & Transplant Hepatology, Duke Gastroenterology. “Currently, treatment-experienced cirrhotic patients still require a 24-week regimen to achieve high SVR rates. The data from this clinical trial using the DCV-TRIO regimen showed high cure rates for this population in a 12-week regimen, and has the potential to aid treatment adherence and provide a shorter treatment duration to achieve cure.”

Study Design and Results

The Phase 3 UNITY clinical trial program is an ongoing study investigating 12-week regimens of the DCV-TRIO fixed-dose combination (daclatasvir 30 mg plus asunaprevir 200 mg plus beclabuvir 75 mg) in non-cirrhotic and cirrhotic genotype 1 patients.

The open-label UNITY-1 study evaluated a 12-week regimen of the DCV-TRIO without ribavirin in treatment-naïve and -experienced non-cirrhotic patients. Non-cirrhotic treatment-naïve patients (n=312) and treatment-experienced patients (n=103) received the DCV-TRIO fixed-dose combination in one pill twice daily for 12 weeks, with 24 weeks of follow-up. The majority of the patients (73%) were genotype 1a, and 91% of all patients achieved SVR12. 92% of treatment-naive patients and 89% of treatment-experienced patients achieved cure, without the use of ribavirin.

In the UNITY-2 study, both cirrhotic treatment-naïve and treatment-experienced patients received the DCV-TRIO fixed-dose combination, one arm without ribavirin (n=102) and one with ribavirin (n=100). The study was double-blinded to ribavirin, and the majority of the patients (74%) were genotype 1a. The study showed 96% of all patients who received the DCV-TRIO with ribavirin achieved SVR12, and 90% of those who received the DCV-TRIO without ribavirin achieved SVR12.

“The Phase 3 UNITY results for the daclatasvir TRIO fixed-dose combination are particularly compelling for genotype 1 patients with cirrhosis, whose treatment is often harder to manage than non-cirrhotic patients,” said Douglas Manion, M.D., head of Specialty Development, Bristol-Myers Squibb. “BMS continues to recognize that HCV is an extremely complicated disease with no ‘one-size-fits-all’ treatment solution, and the UNITY results are especially promising for serving patients with cirrhosis, a specific but significant portion of genotype 1 patients.”

In both UNITY-1 and UNITY-2 there were low rates of adverse events (AEs) leading to discontinuation and of serious adverse events (SAEs) overall. In UNITY-1 there were 7 SAEs, all considered not related to study treatment, and 3 AEs leading to treatment discontinuation. The most common AEs were headache (25.8%) and fatigue (16.6%). In UNITY-2, there were 3 SAEs related to treatment and 4 AEs leading to discontinuation. The most common AEs were headache and fatigue (both 19.8%).

Full abstracts for both presentations are available at The Liver Meeting website.

About Hepatitis C

Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. Approximately 170 million people worldwide are infected with hepatitis C, with an estimated 2.7–3.9 million chronically infected in the United States. Up to 90 percent of those infected with hepatitis C will not spontaneously clear the virus and will become chronically infected. According to the World Health Organization, up to 20 percent of people with chronic hepatitis C will develop cirrhosis; of those, up to 20 percent may progress to liver cancer.

About Bristol-Myers Squibb’s HCV Portfolio

Bristol-Myers Squibb’s research efforts are focused on advancing late-stage compounds to deliver the most value to patients with hepatitis C. At the core of our pipeline is daclatasvir, a potent pan-genotypic NS5A complex inhibitor (in vitro), which continues to be investigated in multiple treatment regimens and in people with co-morbidities.

Daklinza (daclatasvir) was recently approved in the EU for use in combination with other medicinal products across genotypes 1, 2, 3 and 4 for the treatment of chronic hepatitis C virus (HCV) infection in adults. Daklinza is also approved in Japan in combination with Sunvepra (asunaprevir), a NS3/4A protease inhibitor. The Daklinza+Sunvepra Dual Regimen is Japan’s first all-oral, interferon- and ribavirin-free treatment regimen for patients with genotype 1 chronic HCV infection, including those with compensated cirrhosis.

In 2013, Bristol-Myers Squibb’s investigational all-oral DCV-TRIO regimen (daclatasvir/asunaprevir/beclabuvir) received Breakthrough Therapy Designation in the U.S., which helped to expedite the start of the ongoing Phase 3 UNITY program. Study populations include non-cirrhotic naïve, cirrhotic naïve and previously treated patients. In addition to UNITY 1 and 2, both the UNITY-3 study among Japanese treatment-naïve and -experienced genotype 1 patients and UNITY-4, which studies the DCV-TRIO regimen without ribavirin in cirrhotic and non-cirrhotic patients in Korea, Russia and Taiwan, are currently ongoing. The DCV-TRIO regimen is being studied as a fixed-dose-combination treatment with twice daily dosing.

Additional studies with daclatasvir in combination with sofosbuvir are being conducted in high unmet need patients, such as pre- and post-transplant patients, HIV/HCV co-infected patients and patients with genotype 3 as part of the ongoing Phase 3 ALLY Program.

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 daclatasvir or asunaprevir or any other compounds mentioned in this release will receive regulatory approval in the United States, 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, 2013, 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 Company
Media:
Carrie Fernandez, Office: 609-419-5448
Cell: 215-859-2605
carrie.fernandez@bms.com
or
Investors:
Ranya Dajani, 609-252-5330
ranya.dajani@bms.com
or
Ryan Asay, 609-252-5020
ryan.asay@bms.com

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