BioWorld Insight Contributing Writer

The European Committee for Medicinal Products for Human Use's (CHMP) recent positive ruling on InterMune Inc.'s perfenidone for idiopathic pulmonary fibrosis (IPF) raised both hopes and questions.

InterMune's CEO Dan Welch estimates that IPF is a $3 billion market in Europe, and that the drug will have several years of market exclusivity, thanks to its orphan drug status and patent portfolio. InterMune's stock skyrocketed 144.5 percent to $34.89 on the day of the CHMP decision. (See BioWorld Today, Dec. 20, 2010.)

But Welch – and InterMune's investors – are still grappling with one open and pressing question: Will perfenidone have a future in the U.S.?

In May, the FDA rejected the drug, issuing InterMune a complete response letter stating that the company would need to present additional Phase III trial data to be reconsidered for approval. It was a surprising decision, considering an advisory panel had given perfenidone the thumbs up. (See BioWorld Today, May 5, 2010.)

InterMune's executives are reviewing their options, which include appealing the ruling, submitting data from a trial in Japan, or launching a new Phase III trial. They plan to announce their decision sometime in the first quarter of 2011.

Though Welch declined to handicap the various strategies, he made it clear in an interview with BioWorld Insight that the company still hopes to develop perfenidone in the U.S. That's largely because InterMune has secured several new patents, which could extend perfenidone's market exclusivity to 2026 in Europe and 2030 in the U.S. Previously, the drug's orphan status gave it only seven years in Europe and 10 in the U.S.

"So making an investment in perfenidone for IPF and maybe even other indications is now possible, because we don't have seven years, we have nearly 20 years," Welch said. "That's a fantastic value proposition."

Still, some analysts would rather see InterMune appeal the FDA's rejection than invest in gathering more data.

The track record for appeals is mixed, at best. Genta Inc., for example, appealed a rejection of its drug Genasense (oblimersen sodium) for relapsed or refractory chronic lymphocytic leukemia, but the FDA rejected the appeal. Gilead Sciences Inc. also lost an appeal after the FDA rejected its inhaled aztreonam lysine for cystic fibrosis infections, but the drug was later approved following an advisory committee review. Perseverance also paid off for EPIX Pharmaceuticals Inc.'s imaging agent Vasovist (gadofosveset trisodium), which initially lost an appeal, but a second appeal led to a re-review of the data, paving the way for approval.

"The hill is very steep to climb when a company receives a complete response letter," Welch conceded.

But InterMune might have a better shot at an appeal than the average company. The competitive landscape in IPF has changed over the last year. On Dec. 23, Gilead Sciences Inc. halted work on Letairis (ambrisentan) after a failed Phase III trial. In March, a similar drug – Actelion Ltd.'s Tracleer (bosentan) – also failed in Phase III. (See BioWorld Today, Dec. 27, 2010.)

That leaves no currently available treatment options and little in late-stage development for IPF, a disease that causes irreversible lung scarring in about 5 million patients worldwide and is ultimately fatal. The desire to offer patients hope prompted the FDA's advisors to back InterMune's drug despite the fact that only one of two trials met its endpoint.

Welch wouldn't say if he's leaning more toward the appeal option over other strategies, but he did note that the recent European panel win – which is expected to translate to a European approval – could be a positive for the company. "Perfenidone is approved in Japan and it will soon be approved in Europe. You would think that could put some pressure on the FDA," he said.