West Coast Editor

The launch of Phase III trials with its AstraZeneca plc-partnered arthritis compound, PN 400, brings Pozen Inc. back to the table for another try at drug approval, about one month after the FDA smacked the firm with another approval letter for its migraine therapy - about which Pozen refused to take questions during Friday's conference call.

With the start of Phase III studies, PN 400's deal terms have been changed, as well, and Wall Street liked the whole package, pushing Pozen's stock (NASDAQ:POZN) up 28 percent, to close at $12.76, an increase of $2.78.

"Long term, Pozen is going to do very well with this product," said John Plachetka, chairman, Pozen's president and CEO.

London-based AstraZeneca is providing Pozen up to $345 million in development, regulatory and sales milestones, with $30 million right away, $55 million when development and regulatory goals are met and $260 million when sales targets are hit.

Under the original pact, would-be development and regulatory payouts added up to $160 million, of which $20 million was due when proof-of-concept studies finished, and good sales performance would have garnered only as much as $175 million.

The U.S. royalty structure has been revised from the tiered setup to one low-double-digit rate "below the teens" for the life of the agreement, with the royalty structure outside the U.S. slightly revised to a multi-tiered structure that ranges from mid-single digits to high-teens, Plachetka said.

"Changing business conditions" for AstraZeneca brought about the retooling of the deal, Plachetka said. In the spring, the pharma firm disclosed its plan to buy Gaithersburg, Md.-based MedImmune Inc. for $15.2 billion. (See BioWorld Today, April 24, 2007.)

A new drug application is planned for the first half of 2009 for PN 400, a single-tablet combination of esomeprazole magnesium, a proton pump inhibitor, with naproxen, a nonsteroidal anti-inflammatory drug (NSAID).

Chapel Hill, N.C.-based Pozen and AstraZeneca entered their deal for the compound last year. The idea is to come up with an NSAID for arthritis that causes fewer gastric ulcers. Interim results from the study known as PN 200-301 have provided encouragement, and two Phase III trials of 400 patients each are modeled on that study. (See BioWorld Today, Aug. 3, 2006.)

"Because of our business model, we don't spend any more money on these things, once we get to the NDA," Plachetka noted.

PN200-301 enrolled briskly, and Pozen is targeting enrollment in the next studies to finish in about six months. "We certainly hope so, but there are other competing studies out there with other companies at the moment," said Marshall Reece, vice president of product development.

In the second approvable letter for Trexima - Pozen's lead candidate, partnered with London-based GlaxoSmithKline plc - last month, the FDA focused on a Chinese hamster ovary study that showed genotoxicity with high doses of sumatriptan and naproxen sodium in combination but not with either drug alone.

Trexima combines 85 mg of sumatriptan with 500 mg of naproxen sodium.

Pozen said at the time that concerns about the single preclinical genotoxicity study might be resolved with a small, single-dose clinical trial. (See BioWorld Today, April 24, 2007.)