Initial results of a clinical trial testing the safety and efficacy of an experimental hepatitis C therapy suggest that people who've failed to respond to pegylated interferon/ribavirin combination treatment may have better success with this new therapy.1
An Alternative?
The oral therapy being tested is known as valopicitabine (NM283), being developed by Idenix Pharmaceuticals. It's designed to be taken once per day. After 12 weeks of treatment in an ongoing phase 2 study of the medication, patients taking valopicitabine were able to suppress levels of the hepatitis C virus better than those who had been retreated with pegylated (longer-lasting) interferon combined with ribavirin, according to investigators.
The findings were presented at the annual meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco last month.
"At 12 weeks, the combination of valopicitabine plus Pegasys [peginterferon alfa-2a] produced a significant improvement in the suppression of hepatitis C virus (HCV) replication and a significantly higher proportion of patients achieving an early virologic response (EVR) compared to patients retreated with Pegasys and ribavirin," explained Christopher O'Brien, MD, with the Center for Liver Diseases at the University of Miami, and one of the study's key investigators.
Pegasys, made by Hoffman-La Roche Pharmaceuticals, is one of two pegylated interferons offered to people with hepatitis infection. The other, PEG-Intron (peginterferon alfa-2b) is manufactured by Schering-Plough Pharmaceuticals. Both are used in combination with ribavirin.
How The Drug Works
Valopicitabine is a polymerase inhibitor—a drug that blocks an enzyme known as polymerase that the hepatitis C virus to make copies of itself and expand its infection in the body. All of the patients in the ongoing trial have genotype 1 hepatitis C. This is a strain of the virus that is the most common and the least responsive to therapy.2
"These are promising results, particularly for the many [hard-to-treat] patients in urgent need of new therapeutic options," O'Brien stated.
The trial is aimed at evaluating the effectiveness of various doses of valopicitabine combined with pegylated interferon in addition to ribavirin. After three months of therapy, patients taking two higher doses of the medicine in combination with Pegasys showed greater suppression of HCV RNA, a genetic indicator that shows doctors the virus is present, than those who were retreated with Pegasys and ribavirin, O'Brien and his colleagues reported.
In the two groups taking the higher doses of valopicitabine, 63 percent and 71 percent, respectively, achieved an early virologic response, or EVR, defined as a predetermined reduction in viral levels 12 weeks after the start of therapy.3 That compares to just 41 percent of patients achieving an EVR after retreatment with Pegasys and ribavirin, the investigators reported.
Next Steps
While there were some patients who quit the trial due to intolerable side effects or other reasons, the investigators reported they were few. Two serious side effects attributed to the combination of valopicitabine and pegylated interferon—anemia and dehydration—have both been corrected in the trial.
Idenix said it planned to review the data from the phase 2 trial with the Food and Drug Administration (FDA) at the end of November.
"These encouraging data support continued evaluation of combination treatment with valopicitabine and pegylated interferon in both [hard-to-treat] and treatment-naïve [not previously treated] hepatitis C patients," said Nathaniel Brown, MD, executive vice-president of Clinical Development and Chief Medical Officer of Idenix, in a prepared statement. "We look forward to initiating our phase 3 program for valopicitabine in [difficult-to-treat] patients in early 2006."
1. 56th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). 2005 November 11-15. San Francisco, CA.
2. Trepo C. Genotype and viral load as prognostic indicators in the treatment of hepatitis C. J Viral Hepat 2000 Jul;7(4):250-7.
3. Davis GL, Wong JB, McHutchison JG, Manns MP, Harvey J, Albrecht J. Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology 2003 Sep;38(3):645-52.
John Martin is a long-time health journalist and an editor for CuraScript. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
