InterMune Inc. started a Phase III trial to evaluate the once-daily use of Infergen in combination with ribavirin for patients chronically infected with hepatitis C virus who have failed to respond to a previous course of therapy with pegylated interferon alfa-2 plus ribavirin.
The Brisbane, Calif.-based firm was prompted to sponsor the trial following release of data from investigator-initiated studies, which have suggested that a daily dose is efficacious in nonresponders, Griffin Murray, InterMune's corporate spokesman, told BioWorld Today.
"We hypothesize that response rates will be in the 25 percent to 40 percent range for daily use," Murray said, adding that 6 percent to 10 percent of patients who failed first-line therapy respond to second-line therapy.
There are no therapies currently marketed for nonresponders.
Infergen, a bio-optimized Type I interferon-alpha dosed three times a week, is marketed by InterMune as a treatment for adults with chronic HCV infections with compensated liver disease. It is the only interferon-alpha with data in the label regarding use following relapse or non-response to certain previous treatments, the company said.
Standard treatment for chronically infected patients is pegylated interferon alfa-2 plus ribavirin. However, about half of all patients fail to respond. There are about 150,000 nonresponders in the U.S., and the number is growing by an estimated 50,000 each year, InterMune said.
InterMune's revenues from Infergen last year were $9 million. Murray said the company expects revenues in 2004 to range from $17 million to $22 million.
The Phase III study, referred to as DIRECT, is a randomized, open-label, pivotal trial designed to enroll 510 HCV nonresponders at about 40 centers in the U.S. Patients in the first two arms will receive combination therapy of daily Infergen at one of two dose levels (9 mcg or 15 mcg) plus 1,000 mg to 1,200 mg of ribavirin (based on body weight) for up to 48 weeks. The third arm will be a control arm and will serve as the comparison for response rates in the two treatment arms.
The primary endpoint is the proportion of patients with sustained viral response, which is defined as the absence of detectable HCV RNA in serum 68 and 72 weeks after the initiation of treatment. Secondary endpoints are: the proportion of patients with quantitative measurement of serum HCV RNA levels below the level of detection at weeks 24 and 48, and the proportion of patients with abnormal serum alanine transaminase (ALT) levels at baseline, but who have normal ALT levels at various points during the study.
Murray said the trial is expected to take about two and a half years and should be followed by a supplemental biologics license application filing in the disease.
In mid-2001, InterMune paid Thousand Oaks, Calif.-based Amgen Inc. about $29 million (plus royalties on sales) for U.S. rights to Infergen. The transaction gave InterMune rights to develop and commercialize the pegylated interferon version under development by Amgen. (See BioWorld Today, June 18, 2001.)
The FDA approved Infergen as a treatment for HCV in 1997. (See BioWorld Today, Oct. 8, 1997.)
InterMune's stock (NASDAQ:ITMN) Tuesday moved up 51 cents to close at $14.49.