InterMune Inc. reported top-line results from a Phase III trial of Actimmune in the treatment of idiopathic pulmonary fibrosis that, while failing to meet its primary endpoint of progression-free survival, showed a survival benefit.
"The results of the trial are very encouraging, and we are very pleased to be able to have demonstrated a survival benefit for patients with idiopathic pulmonary fibrosis," said InterMune President and CEO Scott Harkonen.
InterMune's stock (NASDAQ:ITMN) rose $4.66 Wednesday, or 25.9 percent, to close at $22.66.
Actimmune already is marketed in the U.S. for chronic granulomatous disease and severe, malignant osteopetrosis.
Harkonen said in a conference call that the study, begun in September 2000, did not achieve statistical significance in reduction of disease progression, although it was "headed in the right direction."
The trial, which included 330 patients, demonstrated an overall 40 percent reduction in mortality (p=0.084). In the patient population, 16 out of 162 deaths were in the Actimmune-treated group, or 9.9 percent, compared to 16.7 percent in the placebo group.
In patients with mild to moderate idiopathic pulmonary fibrosis (IPF), there was a 70 percent decrease in mortality in favor of Actimmune. Of the 254 patients with mild to moderate disease, defined as those with a forced vital capacity of greater than 55 percent, six of 126 people in the Actimmune group died, and 21 of 128 in the placebo group (p=0.0004).
In explaining how the trial could indicate a survival benefit, yet fail to meet its endpoint, Harkonen said that the drug might make IPF patients less vulnerable to exacerbating incidents like bronchitis, a condition they otherwise might not be able to withstand.
"IPF is a progressive disease that leads to loss of lung function followed by death," he said. "Sometimes the disease leads to death without deterioration," due to exacerbating illnesses.
The company plans to submit the data to the FDA in the next few weeks and hopes to have a meeting with the agency before year's end. Whether or not additional trials may be necessary is unclear at this point.
"There are now two controlled trials showing a mortality benefit for patients with IPF treated with Actimmune," Harkonen said.
Thomas Shrader, a biotech analyst with Gerard Klauer Mattison & Co. in New York, said that he doesn't believe the trial will support FDA approval of the drug for IPF.
"I'd be surprised if the FDA approved this," Shrader told BioWorld Today. However, he said that there are examples where the FDA did approve drugs for patients in desperate situations.
InterMune also is enrolling all patients into an open-label trial and will continue to follow the group, he said.
The complete data from the trial will be presented at the European Respiratory Society meeting in Stockholm, Sweden, on Sept. 15. The results also will be presented at the American College of Chest Physicians meeting in November in San Diego, the company said.
The guidance for Actimmune (interferon gamma-1b) sales in 2002 is $90 million to $100 million, Harkonen said. Sales were $40 million in 2001 and were $40 million through the first six months of 2002.
"The sales are basically driven by the strong demand we've already seen in Actimmune sales, driven by the Phase II study," David Cory, InterMune's senior vice president of sales and marketing, said in the conference call.
Shrader estimated sales of about $200 million annually. The cost for one year of Actimmune treatment for IPF is estimated at $50,000.
"The death benefit of today's data helps support that price," Schrader said, noting that the data also make it difficult for physicians not to continue prescribing Actimmune for IPF.
And with anticipated sales at that level, Shrader said the money would pay for the company's other products in development.
"They would never need to raise money again," he said.
Harkonen told BioWorld Today that the data on its first product would enable him to "actually manage the company into profitability into 2004," just about the time InterMune expects its drug, oritavancin, to hit the market.
Like Actimmune, oritavancin, a semisynthetic glycopeptide, is in development for a range of resistant Gram-positive bacterial infections. InterMune in September bought rights to oritavancin from Indianapolis-based Eli Lilly and Co. for at least $50 million, aiming to pair it with Actimmune. (See BioWorld Today, Sept. 21, 2001.)
Actimmune entered Phase III trials for ovarian cancer in February. In cryptococcal meningitis, InterMune reported positive results in December from its Phase II trial with Actimmune as an adjunct to conventional antifungals. The drug brought about more rapid clearance of cryptococcus fungus from cerebral spinal fluid when compared to conventional antifungal therapy alone. (See BioWorld Today, Dec. 19, 2001, and Feb. 6, 2002.)
In April, InterMune Inc. licensed worldwide rights to develop and commercialize Pirfenidone for all fibrotic diseases, including renal, liver and pulmonary. InterMune, of Brisbane, Calif., signed an exclusive license agreement with Marnac Inc., of Dallas, and with the company's co-licensor, KDL GmbH, of Basel, Switzerland. InterMune will make an undisclosed up-front payment and pay milestones, as well as royalties. (See BioWorld Today, April 9, 2002.)
Connetics Corp., of Palo Alto, Calif., acquired Actimmune from Genentech Inc., of South San Francisco, in 1998 and in turn licensed it to InterMune. Genentech received approval to market the drug to treat chronic granulomatous disease in 1990, but Actimmune has since licensed all rights to the drug and it also is now marketed for severe, malignant osteopetrosis. (See BioWorld Today, April 30, 1999.)