As planned, InterMune Inc. started its pivotal Phase III trial testing Actimmune (interferon gamma-1b) against idiopathic pulmonary fibrosis, aiming to enroll 600 patients at about 70 centers in the U.S., Europe and Canada.
In an earlier Phase III trial, the drug failed to meet its primary endpoint of progression-free survival but showed a survival benefit, and the current trial was designed with those results in mind, said James Pennington, vice president of medical and scientific affairs at Brisbane, Calif.-based InterMune. In the new trial, survival time is the endpoint.
"This is going to be a pretty darn long study, but in a chronic disease like IPF, you really need to go a long time to show significant differences," he said.
The company's stock (NASDAQ:ITMN) closed Tuesday at $22.94, up 1 cent.
Called the INSPIRE trial, the randomized, double-blind and placebo-controlled study will evaluate Actimmune in IPF patients with mild to moderate impairment in lung function. It's expected to last about four years, Pennington said.
An interim analysis will be conducted but "we'll have a pretty steep hurdle for stopping the study early," he said, adding that InterMune expects to have the study fully enrolled in two years.
Patients will be randomized at a ratio of 2:1 to receive either 200 micrograms of Actimmune three times a week or placebo, respectively. InterMune designed the trial based on an earlier 330-patient Phase III trial and two other independently conducted studies in Vienna, Austria, and Greece suggesting Actimmune prolongs survival in IPF patients.
In the earlier Phase III trial, "we didn't follow those patients long enough [to prove the endpoint made primary in the new trial] - only for an average of about 18 months," Pennington said. The INSPIRE trial will follow each patient for at least two years and "probably the average time will be three years." (See BioWorld Today, Aug. 29, 2002.)
There is no approved treatment for IPF, the most common form of idiopathic interstitial pneumonia, which afflicts about 83,000 patients in the U.S. and carries a survival time from diagnosis of two to five years, but Actimmune is used off label.
"We're going to ask that these patients be new patients who have not previously received Actimmune," Pennington said. "We want to answer the [survival] question scientifically, in a very fair study where everybody starts from the same point."
How much does InterMune expect to improve survival with the drug?
"I can't speculate on it, because it's going to be a statistical endpoint," Pennington said. "I would love to see an extension of at least a year or more."
The drug's side effects are mainly flu-like symptoms, he said.
"The surprising thing is that, in contrast to the alpha interferons used for hepatitis C virus, the gamma interferon [in Actimmune] has much less of these symptoms," Pennington said. In the first Phase III trial, "we only had about eight patients that dropped out because of side effects," he said.
Actimmune is on the market for chronic granulomatous disease and severe, malignant osteopetrosis. InterMune has the drug in a Phase III study for ovarian cancer and in a Phase II trial for severe liver fibrosis, or cirrhosis, caused by HCV.
Thomas Shrader, analyst with Harris Nesbitt Gerard in New York, called Actimmune "a marginal drug for a very bleak condition. It's a little like the multiple sclerosis drugs. They don't make you better; they make you worsen slightly slower."
But, he said, the Phase III study should help keep Actimmune in the news for a while, and its visibility could help sales.
Pennington pointed out any survival benefit is appreciated by patients.
"We don't anticipate patients needing to cycle through these other therapies" - such as prednisone - which are used off label, he added. "We envision this to be a chronically used drug."
Separately, InterMune disclosed preliminary findings with Actimmune in combination with Infergen (interferon alfacon-1) for chronic HCV patients who failed to show any significant response to peg-interferon alpha-2 plus ribavirin.
Results showed that, in response to the combination therapy, 38 percent of patients had undetectable levels of virus after 12 weeks and 65 percent have experienced a 2 log or greater decline in viral load. Data were presented at the HepDART scientific meeting in Kauai, Hawaii.