Assistant Managing Editor

In pretty short order, the regulatory status of Somaxon Pharmaceuticals Inc.'s insomnia drug Silenor (doxepin) went from having an uncertain timeline to a PDUFA date only two months away, news that surprised Wall Street and sent the company's shares skyrocketing 81.8 percent Friday.

Somaxon's stock (NASDAQ:SOMX), trading at 11 times its normal volume, gained $1.08, to close at $2.40.

After getting a second complete response letter last month, with regulators raising concerns with a "lack of robustness" in efficacy data, investors had been left to wonder whether additional clinical work would be required, what kind of further delay might be expected and how far Somaxon could stretch its shrinking cash balance, which totaled only $5.4 million as of Sept. 30. (See BioWorld Today, Dec. 8, 2009.)

But a Jan. 20 meeting with senior leadership at the FDA dramatically changed the firm's near-term prospects. Without asking for additional safety or efficacy data - instead requiring only the resubmission of a pre-meeting briefing package - the FDA allowed Somaxon to resubmit its application for Silenor the following day and set a new PDUFA date of March 21.

Given the drug's prior regulatory stumbles, Somaxon is remaining somewhat cautious.

"Clearly, we've been working at this some time," Richard Pascoe, president and CEO, told BioWorld Today. But he called the latest news "very positive," and said it was "encouraging to be able to meet with the agency and make some progress."

He added that Somaxon will continue working with regulators over the next two months.

In the meantime, "we're still working our plan," he said, which is to "get approval and find a commercial partner to take it to market as soon as practicable."

Somaxon initially had sought Silenor's approval for both sleep onset and sleep maintenance but, after the FDA's first rejection, decided to drop the onset indication, especially after its market research determined that the vast majority of insomniacs have trouble staying asleep through the night.

The space already is dominated by benzodiazepine drugs like Ambien CR (zolpidem, Sanofi-Aventis Group) and Lunesta (eszopiclone, Sepracor Inc.), but Somaxon is counting on Silenor's mechanism as an H1 antagonist to differentiate it in the market.

Silenor "works on the wakefulness side of the equation," Pascoe said. Rather than shutting down the central nervous system, "it promotes sleep by tamping down histamine levels throughout the night."

It's also not considered a scheduled product, since it does not carry the same addiction risk.

Somaxon has maintained that Silenor's efficacy and safety data have been sufficient from the start. Its first new drug application, the filing of which was delayed for several months after the FDA asked for additional preclinical carcinogenicity data in 2007, met with a complete response early last year. The FDA raised issues with the interpretation of efficacy data, and the company responded with a resubmission including additional analyses. (See BioWorld Today, April 9, 2009.)

While the company hopes eventually to build itself into a specialty firm focusing on psychiatric and sleep disorders, Silenor is its only pipeline product for now.

That wasn't the case in 2005 when Somaxon went public in an $11-per-share offering. At that time, it also had an oral nalmefene formulation in-licensed from BioTie Therapies Corp. and in development for impulse control disorders. And a third candidate, a reformulated version of alcohol dependence drug acamprosate calcium, was in testing for movement disorders. Somaxon has since dropped development of both.

Published  January 25, 2010