Almost a year after signing a $160 million partnership for its migraine drug Trexima, Pozen Inc. launched a Phase III program that could lead to a new drug application filing in the second half of 2005.

The Chapel Hill, N.C.-based company, which focuses mainly on treatments for migraine headaches, developed Trexima by combining sumatriptan and naproxen sodium into a single tablet. The combination, also known as MT 400, showed a marked improvement in sustained pain relief over a currently marketed product and placebo in a Phase II trial.

Pozen intends to conduct two Phase III trials that will evaluate the safety and efficacy of Trexima in treating acute migraine headaches. The company also will conduct a long-term, open-label safety study. The initiation of the program resulted in a $15 million milestone payment from London-based GlaxoSmithKline plc to Pozen, which had $56 million in cash at the end of the first quarter.

"This moves us much closer to a sustainable cash flow, a positive cash flow," said John Plachetka, Pozen's chairman, president and CEO, who added that the company's burn rate is about $20 million to $22 million a year. "And this brings in the opportunity for Glaxo to get this product into the marketplace at the end of 2006, which I think is much faster than people thought."

About 28 million people in the U.S. suffer from migraines, and 75 percent of them are women. The headaches are characterized by sharp pulsating pain on one side of the head, and symptoms include nausea and extreme sensitivity to light and sound. Researchers believe they are caused by acute inflammation surrounding selected blood vessels.

The Phase III trials will be nearly identical in design, each enrolling about 1,000 patients who will be divided into four treatment arms. One arm will test Trexima, while patients in the other three arms will receive placebo, naproxen and sumatriptan. The primary endpoint for the studies will be two-hour relief of migraine symptoms. The first trial will begin next month and the second trial will begin in the fall.

"Because it's a combination product, we also have to demonstrate that Trexima is better than each of its individual components," Plachetka said.

Pozen joined forces with GSK in June last year to develop and commercialize combinations of a triptan (5-HT1B/1D agonist) and a non-steroidal anti-inflammatory drug (NSAID), including the combination that makes up Trexima. Pozen is responsible for all preclinical, clinical and regulatory development activities, while GSK is responsible for formulation, manufacturing and commercialization. (See BioWorld Today, June 13, 2003.)

GSK was chosen as a partner because of its migraine research and commercial base. The company markets the triptans Imitrex (sumatriptan) and Amerge (naratriptan hydrochloride). The $160 million potential value includes an up-front fee and various milestone payments.

Imitrex tablets are approved for the acute treatment of migraines, while the NSAID naproxen sodium is contained in a number of medications to treat rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and juvenile arthritis, among other indications.

Plachetka told BioWorld Today that the market potential for Trexima is "outstanding," and that the company expects to file a new drug application in the second half of 2005 with a potential launch at the end of 2006.

"There is today about $1.7 billion of oral triptan sales in the U.S. and this drug should be better than every existing triptan, so I think it will easily become the market leader," he said. "Right now, Imitrex is the market leader and it's close to $1 billion in sales [in the U.S.]."

In a Phase II trial, Trexima demonstrated a 46 percent improvement in sustained pain relief, compared with a 26 percent improvement in patients on Imitrex, and a 17 percent improvement found in placebo patients.

"It's really a doubling of the therapeutic benefit of the triptan," Plachetka said. "It's quite a remarkable improvement."

Pozen has two other products ahead of Trexima in development. In January, the company filed data from a rat carcinogenicity study needed for the NDA filing for MT 100, an oral first-line therapy to treat migraines. The company filed the NDA in August. It expects an answer from the FDA by the end of this month. (See BioWorld Today, Aug. 1, 2003, and Jan. 29, 2004.)

Last fall, the company received a not-approvable letter for MT 300, its lead migraine product, because it failed to achieve statistical significance on secondary endpoints, relief of nausea, sensitivity to light and sensitivity to sound at two hours. The product did meet its sustained pain-relief primary endpoint. (See BioWorld Today, Oct. 21, 2003.)

Pozen has prepared a response to the FDA as it continues to pursue approval of MT 300.

"I think we put together some very compelling arguments to the FDA, but we'll see what happens," Plachetka said.

Aside from its GSK deal, Pozen has development and commercial alliances with San Diego-based Xcel Pharmaceuticals Inc. for MT 300 and Nycomed Danmark ApS, of Roskilde, Denmark, for the Nordic sales rights to MT 100.

The company's stock (NASDAQ:POZN) rose 20 cents on Tuesday, to close at $10.80.