Despite a vote indicating the panel had mixed views on the efficacy data, the Pulmonary-Allergy Drugs Advisory Committee voted 9-3 in favor of recommending that FDA approve InterMune's pirfenidone to reduce decline in lung function in patients with idiopathic pulmonary fibrosis.

InterMune's NDA is backed by a pair of Phase III trials, but the primary endpoint of absolute change from baseline in percent predicted forced vital capacity at week 72 of treatment was statistically significant in only one of the studies.

Pirfenidone achieved statistical significance in the PIPF-004 trial, with patients receiving the drug experiencing a decline of 8 percent in FVC, compared with 12.4 percent in the placebo arm. In the PIPF-006, pirfenidone slightly outperformed placebo (-9.0 percent to -9.6 percent) but not enough to show a treatment effect (Also see "Pirfenidone Advisory Committee Likely To Hinge On Clinical Meaningfulness Of FVC Test" - Pink Sheet, 5 March, 2010.).

With no drugs approved for IPF, it was difficult for FDA to determine what would prove a candidate's efficacy. Mortality would be the ideal primary endpoint, the agency told InterMune at a 2008 pre-NDA meeting. Change in FVC had not been validated as a surrogate nor was it clear what would constitute a clinically meaningful effect size.

The committee was closely divided on whether the decline in FVC in InterMune's Phase III trials demonstrated a clinically meaningful benefit, voting 7-5 that it had. The panel also voted 9-3 that pirfenidone's safety had been adequately assessed.

Two panel members who voted that meaningful benefit had not been established then went on to vote in favor of the drug's approval.

One, patient representative Karen Gottesman of Pacific Palisades, Calif., said she was in favor of giving IPF patients any hope possible in the face of a terminal disease for which the only effective therapy available is lung transplant.

The other, Leslie Hendeles, professor of pharmacy and pediatrics, University of Florida Health Science Center, cited FDA's review of secondary endpoint data for mortality.

" [For] time to on-treatment IPF-related death, when they pool the data, it shows that it decreases the risk by 50 percent," he said. "I thought to myself, if I got this disease, I would be on the next Delta flight to Japan."

Pirfenidone was approved in Japan in 2008, where partner Shionogi markets it as Pirespa . A dual inhibitor of TGF-beta synthesis and TNF-alpha synthesis, pirfenidone will be marketed as Esbriet if approved in the U.S., where it has a May 4 PDUFA date. The drug also was filed for approval with the European Medicines Agency earlier this month.

-Joseph Haas (j.haas@elsevier.com)

Despite Mixed Views On Efficacy Data, Advisory Committee Recommends Approval Of InterMune's Pirfenidone

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