Roche, InterMune, Inc., And Pharmasset, Inc. Announce: Ground-Breaking Combination Of All-Oral Agents Demonstrates Potential As Hepatitis C Treatment Regimen
Results of the INFORM-1 study were presented during the late-breaker session today at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL) in Copenhagen.
The trial, conducted in centres in New Zealand and Australia, is the first to investigate the combination of two oral antiviral medicines in the absence of weekly injections of interferon, or ribavirin. The results demonstrate for the first time that an oral protease inhibitor and an oral nucleoside polymerase inhibitor can be safely and effectively combined, and thus have the potential to be developed into a new treatment regimen for hepatitis C patients. Roche is developing R7227, a protease inhibitor, with InterMune, and R7128, a nucleoside polymerase inhibitor, with Pharmasset.
Further studies will test the activity and safety of the combination of R7227 and R7128 with and without interferon and/or ribavirin. The current standard of care for HCV is a combination of pegylated interferon plus ribavirin, which delivers overall cure rates of 50-60%.
“These are exciting times in our fight against hepatitis C, and the investigation of the innovative oral treatment regimen in INFORM-1, if validated in further study, may radically change future treatment strategies in our patients with chronic HCV infection,” said Edward Gane, M.D., Associate Professor, University of Auckland and Director, Auckland Clinical Studies Limited. “The initial results from this study of the R7227/R7128 combination raise hopes of the possibility for an interferon-free treatment regimen, as well as the potential for a shorter, more potent interferon-based regimen.”
INFORM-1 Results in Brief
INFORM-1 is a randomized, double-blind, ascending dose Phase I trial which has enrolled a total of 57 patients.
Patients receiving the combination of R7227 and R7128 for 14 days – without pegylated interferon or ribavirin – experienced a median reduction in viral levels of -4.8 to -5.2 log10 IU/mL in the highest doses tested. The addition of R7128 to R7227 resulted in sustained viral load reductions over the dosing period, with ~63% of patients experiencing a decrease in viral levels below the quantification limit of the diagnostic assay (less than 40 IU/mL). Furthermore, 25% of patients in the highest dosage groups were below the limit of detection of virus in their blood (less than 15 IU/mL) after 14 days.
In the early low-dose groups, after only three days of dosing, the mean reduction in viral load levels was 0.6 log10 greater with combination treatment (-2.9), compared to the performance of the individual compounds when administered as a single agent (-0.46 and -1.84 for R7128 and R7227, respectively). This suggests an additive effect for the combination.
The combination was well tolerated over 14 days, with no treatment-related serious adverse events (SAEs), no dose reductions and no discontinuations. Pharmacokinetic analysis confirmed that there were no drug-drug interactions between the compounds.
Next Steps in the Development Program
The companies are now exploring twice-daily dosing of R7227 and higher total daily doses (600 mg twice-daily and 900 mg twice-daily) than those explored in the first patient cohorts of INFORM-1. The companies also plan to explore the innovative DAA combination therapy in “treatment-experienced” patients with HCV, or those who did not achieve a cure with a previous interferon-based treatment.
Other Clinical Studies with R7227 and R7128
In addition to clinical studies of interferon-free combination DAA regimens such as those studied in INFORM-1, R7227 and R7128 each are proceeding rapidly in development in combination with Roche’s PEGASYS® (peginterferon alfa-2a) and COPEGUS® (ribavirin). A Phase IIb study with R7128 has now begun, while a Phase IIb study with R7227 is slated to begin in the summer.
The Foundation and Future of HCV Treatment
Combination therapy of pegylated interferon and ribavirin is the current standard of care for HCV. PEGASYS is the leading treatment for HCV, and also is the pegylated interferon therapy of choice for most HCV antiviral agents in development – including those developed through collaborations with Roche, as well as those developed by other companies. The collaborations with InterMune and Pharmasset position Roche as a leader in developing innovative treatments for HCV.
Dial-In and Webcast Details
InterMune and Pharmasset will host a live webcast of a discussion of the INFORM-1 results from the EASL conference today, Saturday, April 25, 2009, at 7:00 p m. CEST (1:00 p.m. EDT). Participating in the discussion will be Dr. Ed Gane, principal investigator in the INFORM-1 trial. Members of management from Roche, InterMune and Pharmasset will also be available to answer questions. A live webcast and slide presentation will be available through the Investor Relations pages of both InterMune and Pharmasset at www.intermune.com or www.pharmasset.com, respectively. Alternatively, interested parties may access the discussion and ask questions by dialing 888-799-0528 (U.S. & Canada) or 973-200-3372 (International), conference ID # 95452531. A webcast replay will be available approximately three hours after the call and will be archived at www.intermune.com and at www.pharmasset.com.
The teleconference replay will be available for 10 business days following the call and can be accessed by dialing 800-642-1687 (U.S. and Canada) or 706-645-9291 (international), and entering conference ID # 95452531.
The companies recommend logging on at least 15 minutes prior to the start of the webcast to ensure adequate time for any software downloads that may be required.
About R7227 (ITMN-191)
R7227 is a potent, macrocyclic inhibitor of HCV NS3/4A protease activity, and has produced multi-log10 reductions in levels of HCV levels in chronic HCV patients, when administered for 14 days as monotherapy and when combined with PEGASYS and COPEGUS. R7227 was safe and well tolerated in these studies.
InterMune is a biotechnology company focused on the research, development and commercialization of innovative therapies in pulmonology and hepatology. InterMune has a pipeline portfolio addressing idiopathic pulmonary fibrosis (IPF) and hepatitis C virus (HCV) infections. The pulmonology portfolio includes the Phase 3 program, CAPACITY, which is evaluating pirfenidone as a possible therapeutic candidate for the treatment of patients with IPF and a research program focused on pirfenidone analog ITMN-520. The hepatology portfolio includes the HCV protease inhibitor compound R7227 (ITMN-191), a second-generation HCV protease inhibitor research program, and a research program evaluating a new target in hepatology. For additional information about InterMune and its R&D pipeline, please visit www.intermune.com.
R7128, a cytidine nucleoside analog inhibitor of HCV RNA polymerase, is being developed for the treatment of chronic HCV infection. R7128 has shown potent in vivo activity against all of the most common HCV genotypes (1, 2 and 3). R7128 was safe and well tolerated when given with PEGASYS and COPEGUS for up to 28 days.
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is on the development of oral therapeutics for the treatment of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Pharmasset is currently developing three product candidates. R7128, an oral treatment for chronic HCV infection, has completed a 4-week clinical trial in combination with PEGASYS plus COPEGUS through a strategic collaboration with Roche, and is initiating a Phase 2b trial. Racivir, which is being developed for the treatment of HIV in combination with other approved HIV drugs, has completed a Phase 2 clinical trial. PSI-7851, an unpartnered second generation HCV nucleotide analogue recently entered phase 1 studies. Additional information is available on the Internet at http://www.pharmasset.com
Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2008, Roche had over 80,000 employees worldwide and invested almost 9 billion Swiss francs in R&D. The Group posted sales of 45.6 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com.
This news release contains forward-looking statements within the meaning of section 21E of the Securities Exchange Act of 1934, as amended, that reflect the companies’ judgments and involve risks and uncertainties as of the date of this release, including without limitation the statements related to anticipated product development timelines. All forward-looking statements and other information included in this press release are based on information available to the companies as of the date hereof, and the companies assume no obligation to update any such forward-looking statements or information. Actual results could differ materially from those described in the forward-looking statements.
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