Washington Editor

Shares of Pozen Inc. surged about 68 percent Thursday on news that its partnered migraine product, Trexima, met all regulatory endpoints in the second of two pivotal trials, as the company began preparing to file for U.S. approval.

In fact, the data showed that the drug achieved statistical significance in every Phase III measure, and Pozen, of Chapel Hill, N.C., plans to insert those findings into a new drug application scheduled for submission next quarter. That's a turnaround from when the FDA, almost a year ago, delivering Pozen a not-approvable letter for another investigational migraine drug, MT 100.

"We're obviously very excited to have finished the second [Trexima] trial and have positive results," said Bill Hodges, Pozen's chief financial officer. "And based on our meeting with the FDA, to get a response from them that there is no additional data necessary to file, we're ecstatic here."

Those feelings ebbed over to the investment community, which drove up the company's stock (NASDAQ:POZN) $2.41, or 67.9 percent, to close at $5.96.

GlaxoSmithKline plc, Pozen's partner on the drug's development, proposed Trexima as its brand name. Formerly called MT 400, the product is a combination of sumatriptan (Imitrex, from GSK) formulated with GSK's RT Technology and naproxen sodium in a single tablet.

When its Phase III migraine program began last year, Pozen earned a $15 million milestone from its London partner. There also is an ongoing long-term, open-label safety study. (See BioWorld Today, May 19, 2004.)

The NDA plans stem from a recent meeting Pozen had with the FDA to discuss the results of both Phase III trials and other information required for the submission. Those discussions have led the company to believe that no additional preclinical or clinical trials are necessary. FDA acceptance of the NDA would trigger a $20 million milestone payment from GSK.

The latest Phase III data demonstrated Trexima's superiority over its individual components, sumatriptan and naproxen, as the primary endpoint. The drug also met all regulatory endpoints for a new migraine product.

For the combination, Trexima demonstrated a superior sustained pain-free response compared to naproxen (p<0.001) and sumatriptan (p=0.009). With respect to pain relief and the associated symptoms of nausea, photophobia and phonophobia, Trexima was superior to placebo at two hours for all parameters (p=0.007 for nausea, p<0.001 for the others).

In the first Phase III study, Trexima didn't reach statistical significance for the nausea endpoint compared to placebo at two hours, but did at three hours and maintained superiority through 24 hours. Hodges called the nausea-free endpoint "our only potential concern going into the FDA," but said the agency did not take issue with the data.

Other findings from the first Phase III study mirrored those from the second, demonstrating Trexima's superiority over the individual components measured by sustained pain-free response (p<0.001), and all other regulatory endpoints were met.

"There are basically six endpoints that we were trying to hit," Hodges said, "which is pretty difficult to do."

In total, the four-arm pivotal studies involved about 2,800 patients and were designed identically. The accompanying open-label safety study has completed its six-month phase, with 12-month data still to come. The trial enrolled more than 500 patients at its outset; Hodges said the FDA required 300 through six months and 100 after a year.

All those data contrast with the NDA for MT 100, the migraine drug that generated a not-approvable letter. That product, a combination of naproxen sodium and metoclopramide, did not clearly meet certain criteria and failed to show superiority over naproxen for sustained pain relief. In its rejection, the FDA also raised safety issues related to risks of tardive dyskinesia, a side effect that causes involuntary movement, usually of the face and tongue. (See BioWorld Today, June 2, 2004.)

Prior to that, the company received another not-approvable letter for a different migraine product, MT 300. A new formulation of dihydroergotamine mesylate in a pre-filled syringe, it failed to achieve statistical significance in relief of secondary symptoms, including nausea, sensitivity to light and sensitivity to sound at two hours. (See BioWorld Today, Oct. 21, 2003.)

"Trexima is just a better drug," Hodges said, later adding that the company is in talks with the FDA to determine whether MT 100 or MT 300 could again move forward down the road. Both parties are working to schedule an advisory committee meeting to address MT 100's association to tardive dyskinesia.

Terms of the Trexima collaboration, which could be worth $160 million to Pozen, call for it to be responsible for all preclinical, clinical and regulatory development activities. GSK is responsible for formulation, manufacturing and commercialization. (See BioWorld Today, June 13, 2003.)

GSK is positioning Trexima as a follow-on to Imitrex, which last year generated $900 million in U.S. sales. The agreement between Pozen and GSK is focused only on the U.S., so Pozen now is seeking a European partner.

Beyond its latest migraine drug development activities, Pozen has produced positive clinical results in its PN program, which combines PPI drugs with NSAIDs to provide control of pain and inflammation with fewer gastrointestinal complications compared to an NSAID taken alone. Initial clinical studies have produced positive results, Hodges said.