EASL-TMC435 Demonstrates Statistically Higher Viral Cure Rates (SVR24) Compared to Placebo in HCV Patients Who Had Failed Prior Treatment

Once-daily TMC435 Demonstrates Statistically Higher Viral Cure Rates (SVR24) Compared to Placebo in HCV Patients Who Had Failed Prior Treatment

-- Janssen R&D Presents Final Safety and Efficacy Results from Phase 2b ASPIRE Study of Once-daily TMC435 at EASL --

BARCELONA, Spain, April 19, 2012 /PRNewswire/ -- Janssen R&D Ireland today will present final results from ASPIRE, a phase 2b study of TMC435, a once daily investigational hepatitis C virus (HCV) NS3/4A protease inhibitor. Results show that the medication was effective and well-tolerated when given in combination with pegylated-interferon and ribavirin (PegIFN/RBV) in the treatment of chronically-infected genotype 1 HCV patients who had failed previous treatment. The data are featured in an oral presentation at the 47th Annual Meeting of the European Association for the Study of the Liver (EASL) in Barcelona, Spain, April 18-22, 2012.

Results from the final ASPIRE analysis show that TMC435 administered in combination with PegIFN/RBV resulted in significantly higher sustained virologic response (SVR24) rates compared to placebo plus PegIFN/RBV. The ASPIRE study evaluated chronically-infected genotype 1 HCV patients who had relapsed, showed partial response, or no response after a prior course of PegIFN/RBV. In the TMC435 arms, 53 to 68 percent of patients achieved rapid virologic response [RVR; HCV RNA<25 (undetectable)], compared to 2 percent of the placebo group. For patients in the TMC435 treatment groups dosed with TMC435 100 mg and 150mg, 61-70 percent of patients and 67-80 percent of patients achieved SVR24, respectively, compared to 23 percent of patients achieving SVR24 in the placebo arm. For null-responders to prior HCV therapy dosed with TMC435 150 mg, 51 percent of patients in the TMC435 treatment groups achieved SVR24, compared to 19 percent in placebo group. When treated with TMC435 150 mg, 75 percent of prior partial responders and 85 percent of patients who previously relapsed reached SVR24, versus 9 and 37 percent taking placebo, respectively. Once-daily TMC435 was well tolerated in this population with comparable incidence of adverse events between TMC435 and placebo groups except for influenza-like illness, pruritus, and rash (any type). Results showed comparable on treatment changes in hemoglobin levels and neutrophil counts between groups and mild, isolated and reversible increases in bilirubin amongst TMC435 treated subjects.

TMC435 150 mg administered once daily (q.d.) is being investigated in phase 3 trials in various patient populations. Two global randomized trials investigate adults with chronic genotype 1 hepatitis C infection – QUEST-1 (TMC435-C208) and QUEST-2 (TMC435-C216) compare TMC435 in combination with PegIFN/RBV against a placebo among treatment-naive adults, and PROMISE (TMC435-C3007) compares TMC435 combined with PegIFN/RBV versus PegIFN/RBV alone in patients who have experienced a viral relapse following previous interferon-based treatment. The recently-launched global phase 3 study HPC3001 assesses TMC435 versus telaprevir, both in combination with PegIFN/RBV, in treatment-experienced patients. Additionally, the global phase 3 trial HPC3011 tests the safety and efficacy of TMC435 in treatment-naive or treatment-experienced HCV genotype 4 infected patients. The phase 3 program in Japan evaluates the efficacy and safety of TMC435 in treatment-naive, relapsed patients, partial and null responders.

"Chronic hepatitis C is a devastating disease for millions of patients infected worldwide and while considered curable, some patient populations remain almost unresponsive to current antiviral therapy, including those with advanced cirrhosis," said Stefan Zeuzem, M.D., lead clinical investigator and Professor of Medicine and Chief of the Department of Medicine, at the Goethe University Hospital, Frankfurt, Germany. "We are encouraged by the results of once-daily TMC435 in combination with peginterferon alfa and ribavirin in achieving significantly higher sustained virologic response rates compared with peginterferon alfa and ribavirin alone in patients who have not had success with previous antiviral treatments. This analysis reinforces the superior viral cure rates to placebo and promising safety profile seen in the phase 2b PILLAR study in treatment-naive patients."

TMC435 is being developed by Janssen Research & Development in partnership with Medivir.

"Janssen is pleased to present the final analysis of the phase 2b ASPIRE study at EASL. The continued development of TMC435, which is currently being investigated in registrational phase 3 studies in both treatment-naive and treatment-experienced patients, reinforces our strong commitment to the development of new therapies that will improve the lives of those impacted by HCV, including patients whose disease is particularly difficult to treat," said Maria Beumont, M.D., Global Medical Leader TMC435 at Janssen.

About the ASPIRE Study

The ASPIRE study (TMC435-C206) was a seven-arm, global phase 2b randomized, double-blind, placebo controlled study that evaluated the effect of TMC435 in combination with pegylated-interferon and ribavirin (PegIFN/RBV). The study was comprised of 462 patients infected with genotype-1 hepatitis C virus who had failed prior treatment with PegIFN/RBV, meaning patients that had relapsed, achieved partial response, or achieved no response (null responders) to PegIFN/RBV treatment.

Patients were equally randomized to one of seven different treatment arms, six groups taking TMC435 and one placebo arm. TMC435 was administered once daily at a dose of either 100 mg or 150 mg given for either 12, 24, or 48 weeks in combination with PegIFN/RBV. PegIFN/RBV treatment was continued in the groups that received TMC435 for 12 or 24 weeks. Total treatment duration was 48 weeks in all patients.

For all patients treated in the TMC435 groups dosed with 100 mg and 150 mg, the most common adverse events were headache (31, 40 percent and 36 percent for TMC435 100mg, TMC435 150 mg and placebo, respectively), fatigue (47, 41 and 44 percent, respectively), influenza-like illness (35, 24 and 20 percent, respectively), pruritis (34, 35 and 17 percent) and neutropenia (23, 28 and 17 percent, respectively). Most adverse events were mild to moderate in severity. Adverse events leading to treatment discontinuation of TMC435/placebo were reported in 7 to 9 percent of patients in TMC435 arms and 5 percent in placebo arm.

Other Janssen R&D Presentations at EASL
In conjunction with the final sustained virologic response (SVR24) results from ASPIRE, Janssen R&D is presenting virology analysis data from ASPIRE, a comparison of two quantitative HCV RNA assays and a study evaluating potential photosensitivity associated with TMC435:

• "TMC435 in patients infected with HCV genotype 1 who have failed previous pegylated interferon/ribavirin treatment: virologic analysis of the ASPIRE study." O. Lenz. (Oral)
• "Comparison of two quantitative HCV RNA assays in samples from patients treated with a protease inhibitor-based therapy: implications for response guided therapy." B. Fevery. (Oral)
• "Absence of photosensitivity potential of TMC435 in healthy volunteers." A. Simion. (Poster)

About HCV
HCV is a blood-borne infectious disease that affects the liver. With an estimated 210 million people infected worldwide and three to four million people newly infected each year, HCV puts a significant burden on patients and society. Chronic infection with HCV can lead to liver cancer and other serious and fatal liver diseases, and is the most common cause of liver transplant worldwide. Pegylated interferon combined with ribavirin can cause serious side effects and only leads to sustained viral clearance in 40 to 50 percent of genotype 1 patients. The development of new therapies, particularly direct antivirals with different modes of action, may allow HCV patients to undergo a shorter and more effective treatment regimen.

About Janssen R&D Ireland
Janssen R&D Ireland, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, is a global pharmaceutical and research development company. The Company's main research and development facilities are in Beerse, Belgium with offices in Titusville, New Jersey and Cork, Ireland. The Company is dedicated to the discovery and development of innovative HIV/AIDS and hepatitis C drugs, and anti-infectives for diseases of high unmet medical need.

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