Findings from Two Phase 3 Studies of Janssen's Simeprevir Administered Once Daily Demonstrate Sustained Virologic Response in Genotype 1 Chronic Hepatitis C Patients

AMSTERDAM, April 23, 2013 /PRNewswire/ -- Janssen R&D Ireland (Janssen) today announced primary efficacy and safety results from two global Phase 3 studies demonstrating that use of the investigational protease inhibitor simeprevir (TMC435) led to sustained virologic response 12 weeks after the end of treatment (SVR12) in 80 and 81 percent, respectively, of treatment-naive genotype 1 chronic hepatitis C adult patients with compensated liver disease, including all stages of liver fibrosis, when administered once daily with pegylated interferon and ribavirin. In both studies, 50 percent of patients receiving pegylated interferon and ribavirin alone achieved SVR12.

The data will be presented this week at The International Liver Congress 2013 of the European Association for the Study of the Liver (EASL) in Amsterdam, The Netherlands. The QUEST-1 and QUEST-2 data will be discussed in an official EASL press conference on April 24 at 11:00 a.m. CEST.

"More than 390 treatment-naive genotype 1 hepatitis C patients in 39 countries received simeprevir as part of the Phase 3 QUEST trials," said Michael Manns, M.D., professor and chairman, Department of Gastroenterology, Hepatology and Endocrinology, Medical School of Hannover. "I am pleased to be a part of these robust studies and look forward to seeing the results from upcoming trials of simeprevir in treatment-experienced patients later this year."

In QUEST-1 and QUEST-2, patients were randomized to receive simeprevir or placebo for 12 weeks plus pegylated interferon and ribavirin for 24 or 36 weeks. In findings related to a secondary endpoint, 85 percent (QUEST-1) and 91 percent (QUEST-2) of patients receiving simeprevir were able to shorten therapy with pegylated interferon and ribavirin to 24 weeks due to meeting response-guided therapy (RGT) criteria. Of those patients meeting RGT criteria to stop treatment at 24 weeks, 91 percent (QUEST-1) and 86 percent (QUEST-2) of patients achieved SVR12.

"Given the long-term health risks associated with hepatitis C, it's important that physicians and patients have multiple options to treat the disease," said Ira Jacobson, M.D., 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 results of these Phase 3 trials suggest that simeprevir could represent an important new treatment option for people living with genotype 1 chronic hepatitis C."

Patients enrolled in QUEST-1 and QUEST-2 were stratified by HCV genotype 1 subtype and IL28B genotype. In QUEST-1, SVR12 rates among patients treated with simeprevir with IL28B genotype variations were 94 percent for the CC allele, 76 percent for the CT allele, and 65 percent for the TT allele. In QUEST-2, SVR12 rates among patients treated with simeprevir with IL28B genotype variations were 96 percent for the CC allele, 80 percent for the CT allele, and 58 percent for the TT allele. Among patients with METAVIR scores F3 and F4, 70 percent of patients treated with simeprevir in QUEST-1 and 66 percent of patients treated with simeprevir in QUEST-2 achieved SVR12. Among patients with METAVIR scores F0 to F2, 83 percent of patients treated with simeprevir in QUEST-1 and 85 percent of patients treated with simeprevir in QUEST-2 achieved SVR12. The METAVIR score is used to quantify the degree of inflammation and fibrosis of the liver and patients are scored on a four-point scale. 

"Patient response rates to hepatitis C therapy can be variable, depending on factors such as viral genotype and subtype, and liver fibrosis. Patients with genotype 1a, IL28B genotype TT and METAVIR scores of F3 and F4 can be particularly challenging to cure," said Maria Beumont, M.D., medical leader for simeprevir, Janssen. "Janssen is committed to advancing hepatitis C therapy for even the most difficult-to-cure patients."

The most common adverse events seen in patients receiving simeprevir in QUEST-1 were fatigue (42 percent versus 41 percent for placebo), itch (26 percent versus 16 percent for placebo), and headache (33 percent versus 39 percent for placebo). The most common adverse events seen in patients receiving simeprevir in QUEST-2 were fatigue (37 percent versus 42 percent for placebo), itch (25 percent versus 25 percent for placebo), headache (39 percent versus 37 percent for placebo), fever (31 percent versus 40 percent for placebo), and influenza-like illness (26 percent versus 26 percent for placebo). In QUEST-1, in both the simeprevir and placebo arms, 3 percent of patients discontinued treatment due to an adverse event. In QUEST-2, 2 percent of patients in the simeprevir arm and 1 percent of patients in the placebo arm discontinued treatment due to an adverse event.

About QUEST-1 and QUEST-2

QUEST-1 and QUEST-2 are global, Phase 3, randomized, double-blind, placebo controlled clinical trials assessing the efficacy, safety and tolerability of simeprevir plus pegylated interferon and ribavirin versus pegylated interferon and ribavirin alone in treatment-naive adult patients with genotype 1 chronic hepatitis C with compensated liver disease, including all stages of liver fibrosis.

In the QUEST-1 and QUEST-2 trials, 394 and 391 patients, respectively, were randomized to receive one 150 mg capsule of simeprevir or placebo once daily plus pegylated interferon and ribavirin for 12 weeks, followed by pegylated interferon and ribavirin alone for either 12 or 36 weeks based on RGT criteria. Patients in the simeprevir arm were considered to have met RGT criteria if their HCV RNA levels were <25 IU/mL (detectable or undetectable) at week 4 and <25 IU/mL undetectable at week 12. In patients meeting RGT criteria, HCV therapy was stopped at week 24. All other patients continued treatment until week 48.

About Simeprevir

Simeprevir (TMC435) is an investigational NS3/4A protease inhibitor jointly developed by Janssen 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 is believed to work by blocking the protease enzyme that enables the hepatitis C virus to survive and replicate in host cells. Janssen recently announced the submission of new drug applications for simeprevir in Japan and the United States for the treatment of genotype 1 hepatitis C, and anticipates submitting simeprevir for regulatory authorization in the EU in the first half of 2013.

Global Phase 3 studies of simeprevir include QUEST-1 and QUEST-2 in treatment-naive adult patients, PROMISE in patients who have relapsed after prior interferon-based treatment and ATTAIN in null-responder adult patients. In parallel to these trials, Phase 3 studies for simeprevir are ongoing in treatment-naive and treatment-experienced HIV-HCV co-infected patients and HCV genotype 4 patients. To date, 1,846 patients have been treated with simeprevir in clinical trials.

Simeprevir is also being studied in Phase 2 interferon-free trials with and without ribavirin in combination with:

• Janssen's non-nucleoside inhibitor TMC647055 and ritonavir in treatment-naive genotype 1a and 1b HCV patients;
• Gilead Sciences, Inc.'s nucleotide inhibitor sofosbuvir (GS-7977) in treatment-naive and previous null-responder genotype 1 HCV patients; and
• Bristol-Myers Squibb's NS5A replication complex inhibitor daclatasvir (BMS-790052) in treatment-naive and previous null-responder genotype 1 HCV patients.

In addition, Janssen has entered into a non-exclusive collaboration with Vertex Pharmaceuticals to evaluate in a Phase 2 study the safety and efficacy of an all-oral regimen of simeprevir and Vertex's investigational nucleotide analogue polymerase inhibitor VX-135 for the treatment of HCV. As a first step, Janssen is conducting a drug-drug interaction (DDI) study with simeprevir and VX-135. Janssen also has plans to initiate a Phase 2 trial of an investigational interferon-free regimen with simeprevir, TMC647055 and Idenix's IDX719, a once-daily, pan-genotypic NS5A inhibitor, with and without ribavirin.

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

About Hepatitis C

Hepatitis C, a blood-borne infectious disease of the liver and a leading cause of chronic liver disease, is the focus of a rapidly evolving treatment landscape. Approximately 150 million people are infected with hepatitis C worldwide and 350,000 people per year die from the disease globally. When left untreated, HCV 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 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; 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.)

SOURCE Janssen R&D Ireland

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