An FDA panel Thursday unanimously recommended approval of Hoffmann-La Roche Inc.'s proposal to use Pegasys in combination with Copegus for the treatment of chronic hepatitis C.
The decision by the Antiviral Drugs Advisory Committee in Bethesda, Md., came one day after FDA staff released a 59-page briefing document in which it described the proposed combination therapy as "superior to peginterferon alfa-2a monotherapy."
Peginterferon alfa-2a, or Pegasys, a pegylated interferon, was approved in October by the agency for hepatitis C. Roche, of Nutley, N.J. received priority review status for the Pegasys plus Copegus application. (See BioWorld Today, Oct. 18, 2002.)
While Pegasys is the PEGylated (stays in the body longer) version of Roferon, a Roche product administered subcutaneously three times a week for hepatitis C, Copegus is actually Roche's ribavirin.
Roche presented the panel with data from two trials, the first being NV15801, designed to compare Pegasys plus Copegus with Rebetron, Schering-Plough Corp.'s version of ribavirin in combination with interferon alfa-2b.
NV15801 was a randomized, multicenter, international, partially blinded, controlled study that included 1,149 treatment-na ve patients who were assigned to peginterferon alfa 2a monotherapy, peginterferon alfa 2a combined with ribavirin, or Rebetol/Intron A.
Efficacy endpoints for both NV15801 and the second Phase III, NV15942, were sustained virological response (no detectable virus) assessed six months after the end of treatment.
The FDA's comment describing the combination therapy as superior references trial NV15801. According to the agency, "The treatment difference is approximately 20 percent absolute."
Study NV15942 was designed to build on the results of NV15801, by using the combination arm from NV15801 to assess the benefits and risk of lower exposures in patient subgroups. The 1,311-patient study was randomized, multicenter, international and double blinded.
According to the FDA, the study "confirmed the association between lower response to treatment and the following factors: hepatitis C virus genotype and titer, cirrhosis, older age, increased body weight, African-American origin, U.S. participants."
Furthermore, the agency said end-of-treatment virologic response in patients treated for 24 weeks appeared to be higher than the end-of-treatment virologic response for patients treated for 48 weeks, irrespective of HCV genotype.
If Pegasys plus Copegus makes it to market, the combination would compete with Schering-Plough's PEG-Intron, a longer-acting form of Intron A that uses pegylation developed by Enzon Inc., of Piscataway, N.J.
Roche worked with Inhale Therapeutics Inc., of San Carlos, Calif., to develop its PEGylated version of Roferon. (See BioWorld Today, Oct. 18, 2002.)
Ribavirin is owned by Ribapharm Inc., of Costa Mesa, Calif., a spin-off of ICN Pharmaceuticals Inc., also of Costa Mesa. (See BioWorld Today, April 15, 2002.)