West Coast Editor

Once-hurting Pozen Inc. got whopping relief from AstraZeneca plc in the form of a potential $375 million deal, with $40 million up front, to develop fixed-dose combinations of naproxen and AstraZeneca's esomeprazole for chronic pain.

Under the terms, Pozen could take in $160 million in development and regulatory milestones, and another $175 million if sales goals are met. The deal also includes tiered royalties ranging from the mid-single digits to the mid-teens.

"It's very similar in a lot of ways to the deal with [GlaxoSmithKline plc for the migraine drug Trexima], but with a much larger potential audience," said John Plachetka, president and CEO of Chapel Hill, N.C.-based Pozen.

Wall Street hailed the deal, which could exceed in payments Pozen's $218 million market cap, and the company's stock (NASDAQ:POZN) closed Wednesday at $10.44, up $2.95, nearly 40 percent.

The idea behind the collaboration is to come up with a pain drug that works but does not bedevil its users with gastrointestinal side effects that make them loath to pop the pill - an important feature for patients with osteoarthritis or rheumatoid arthritis, many of whom pop a lot of pills.

Esomeprazole is the active ingredient in London-based AstraZeneca's Nexium, the best-selling drug for heartburn and stomach ulcers; naproxen is the non-steroidal anti-inflammatory drug (NSAID) familiar to users of over-the-counter pain remedies such as Aleve, and works by blocking cyclooxygenase, the enzyme that makes prostaglandins.

AstraZeneca now owns exclusive rights to what Pozen calls its PN products platform, which combines a proton pump inhibitor (such as esomeprazole) with an NSAID in a single "smart" tablet. In April, Pozen said another compound from the platform, PN 200, had gained a special protocol assessment from the FDA.

PN 200, for the signs and symptoms of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis in patients at risk for developing NSAID-associated gastric ulcers, combines omeprazole with naproxen. Pozen intends to ask the FDA for the go-ahead to use the same SPA in testing the AstraZeneca pain tablet.

"We had talked to the FDA about substituting a different PPI [in PN 200]," and the agency had no problem with it, Plachetka noted.

Pozen and AstraZeneca will co-fund the development program, with Pozen responsible for U.S. regulatory filings. Phase III trials are expected to kick off next year, with a new drug application likely at the end of 2008, the companies said, which means a launch could take place in 2009. AstraZeneca will handle ex-U.S. development, plus worldwide manufacturing, marketing, sales and distribution.

News of the AstraZeneca deal comes a day after word from Pozen that the firm plans to submit next quarter a full response to FDA's approvable letter for the migraine drug Trexima, including more safety information. On the day the letter was disclosed in June, Pozen's stock plunged 60 percent, ending at $5.52, but with Monday's headlines about the company's response, its stock had recovered nicely to $7.70. (See BioWorld Today, June 12, 2006.)

"We have a very clear path to follow at FDA," Plachetka said. "We've shown them most of the data that we're going to put in our full response, and after seeing that data, they said they didn't need any new data, which was great. But we're still coordinating the efforts of [Pozen with GSK]."

Trexima pairs 85 mg of sumatriptan with 500 mg of naproxen in a single tablet and targets dual mechanisms of migraine: inflammation and vasodilation. Sumatriptan, which works on the blood vessels, is the active ingredient in Imitrex, the leading acute migraine treatment, marketed by Pozen partner GSK, of London.

Efforts to advance Trexima and other compounds have sent Pozen's stock on a wild ride over the past 52 weeks, with prices ranging from $5.26 to $18.62. But investor eyes focused Wednesday less on Trexima, for once, than on the prospects of the deal with AstraZeneca, which also stands to gain in more than one way if the arrangement bears fruit. The "purple pill" Nexium, while still selling about $5 billion per year, faces competition and price pressure, and deploying its active ingredient in a new therapy with Pozen could keep the drug going strong for a longer period.

Not included in Pozen's deal with AstraZeneca, and not much talked about, is the firm's PA program, which combines aspirin with a PPI for cardiac protection and to prevent colon cancer, without the ulcers that aspirin can cause.

The PA program is "completely off the radar screen for most analysts," Plachetka said - just as PN once was - but represents a "huge" opportunity that Pozen will seek to partner, after achieving proof of concept next spring.

"It obviously carries with it some challenges," he said. "People think aspirin is cheap and doesn't cause any problems." Also, the data showing the drug's value in blocking colon cancer, though compelling, have not been covered much by the lay press.

But the same patent suite and technology used for PN, "vetted already by AstraZeneca," works with PA, Plachetka said.

"The way we got the SPA for the PN products was to demonstrate bioequivalence to the NSAID, with fewer ulcers, and the approach will be the same for PA," he said, calling the program "ideal" for a partner with interests in the area. Pozen will shop for one.

"It's not over after PN," Plachetka said.