Staff Writer

After more than a year of FDA appeals regarding its once-daily formulation of the analgesic tramadol, Labopharm Inc. got some good news regarding its second product candidate, a once-daily formulation of the antidepressant trazodone.

The Laval, Quebec-based company said a randomized, double-blind Phase III trial comparing once-daily trazodone to placebo in 412 patients with major unipolar depressive disorder met its primary endpoint of improving scores on the Hamilton Rating Scale for Depression (p=0.0183).

The news boosted Labopharm's shares (NASDAQ:DDSS) 17.2 percent, pushing the stock up 34 cents to close at $2.32 on Friday.

Although detailed data won't be unveiled until a later date, Labopharm said the trial's dropout rate of 25.5 percent was comparable to other depression studies, with 21 percent dropping from the placebo group and 30.2 percent from the once-daily trazodone group. Of the treated patients to drop out of the trial, 4 percent cited somnolence or sedation as the reason.

Labopharm also said that once-daily trazodone significantly improved patient sleep patterns in the Phase III trial. That could be an important differentiator against generic trazodone, a dual serotonin agonist and serotonin reuptake inhibitor that is intended to improve depression-disrupted sleep. But whether or not the sleep pattern data will make it into the label for once-daily trazodone remains to be seen.

Mark D'Souza, chief financial officer of Labopharm, said the company plans to file a new drug application under the 505(b)(2) pathway in the second half of the year.

While the FDA indicated that one placebo-controlled Phase III trial would be sufficient for the filing, D'Souza said he didn't know if the agency would allow the sleep pattern data to be used as a differentiator.

He added that post-marketing studies comparing once-daily trazodone to the generic version or to other depression drugs are "something we'll consider" to establish further differentiation.

D'Souza also said that while Labopharm has received partnering inquiries about once-daily trazodone, the company decided to wait for the Phase III data before "aggressively moving" to sign any marketing deals. That process now can begin moving forward.

Labopharm already has a development partnership for the drug with Italian pharmaceutical firm Gruppo Angelini, the original creators of trazodone. Gruppo also is the company's marketing partner for once-daily tramadol in several European countries.

Although once-daily tramadol has gained approvals outside of the U.S., its path with the FDA has been bumpy. Labopharm received two approvable letters for the drug, both of which it unsuccessfully appealed through the agency's dispute resolution process. (See BioWorld Today, Oct. 2, 2006, and June 4, 2007.)

Yet the latest news offered a glimmer of hope. Last month, Labopharm reported that John Jenkins, director of the FDA's Office of New Drugs, suggested that an additional statistical analysis of existing data potentially could satisfy the agency's requirements. D'Souza said the company expects to conduct the new analysis "as quickly as possible."

Elsewhere in its pipeline, Labopharm is preparing to enter Phase III trials with a tramadol-acetaminophen combination formulation. The company also has preclinical programs focused on reformulating intravenous cancer drugs as pills and developing abuse-resistant formulations of opioids. Labopharm previously reformulated the anesthetic propofol but is seeking a partner prior to beginning clinical trials.