The FDA placed a hold on DOV Pharmaceutical Inc.'s pivotal Phase III trial for an anti-anxiety candidate, asking for additional safety data.
Ocinaplon, the subject of the trial, is a molecule thought to selectively modulate a specific subset of GABA-A receptors that DOV believes are involved in the mediation of anxiety.
DOV, of Hackensack, N.J., was poised to begin the Phase III immediately, but the government's move stops it in its tracks.
"We had all the sites lined up and we were just waiting for the FDA to give us the release, and then we got the news that we could not start the trial," Arnold Lippa, DOV's CEO, told BioWorld Today.
DOV's stock (NASDAQ:DOVP) fell $3.54 Friday, or 20.2 percent, to close at $13.95.
Lippa would not discuss details of safety issues or additional information requested by the agency. Instead, he said the FDA had provided the company with certain guidelines on information that can be submitted. "We are in the process of getting that information together," he said.
When asked about timelines related to the submissions and a possible trial start date, Lippa declined comment.
The Phase III is a 500-patient, multidose, placebo-controlled U.S. study of three ocinaplon doses vs. placebo.
Ocinaplon performed well in two Phase II trials, producing a statistically significant reduction in anxiety. Both trials were double-blind, placebo-controlled studies in which ocinaplon exhibited efficacy, a rapid onset of action, a favorable side effect profile not significantly different from placebo and no rebound anxiety following treatment cessation, the company said.
It has been reported that one Phase II patient experienced clinically significant elevated liver enzymes and jaundice. When asked about that, Lippa said the patient was hospitalized and recovered. He also said it is not uncommon to see such elevations in placebo patients, but would not discuss whether that incident from two years ago had anything to do with the FDA's decision to place a hold on the trial.
The first Phase II trial evaluated the effects of an immediate-release formulation of ocinaplon in 60 generalized anxiety disorder (GAD) patients. Ocinaplon demonstrated a statistically significant reduction of anxiety during the four-week study period using several anxiety measurements, including the Hamilton Anxiety Scale, a standard anxiety measurement scale used in clinical trials.
In a second Phase II completed in November 2002, DOV evaluated two controlled-release formulations of ocinaplon. The 14-day study evaluated 117 patients.
Ocinaplon is being developed through a joint venture between DOV and Elan Corp. plc, of Dublin, Ireland. DOV owns 83 percent of the venture and Elan owns 17 percent, Lippa said.
Of the trial freeze, Lippa said, "We're disappointed by this turn of events and we intend to work very closely with the FDA to help resolve it. At the same time, we have a considerable clinical pipeline."
Neurocrine Biosciences Inc., of San Diego, is developing DOV's indiplon, an insomnia candidate in Phase III trials. Pfizer Inc., of New York, signed on as Neurocrine's worldwide development and commercialization partner for the product. When signed in December 2002, the deal was valued at $400 million for Neurocrine. DOV would be due royalties on sales. The companies are expected to file a new drug application in the first half of 2004. (See BioWorld Today, July 10, 1998, and Dec. 20, 2002.)
Another DOV product, bicifadine, a non-narcotic analgesic, is being studied in pain. In recent weeks, DOV released positive efficacy and safety data from a Phase III in moderate to severe post-surgical dental pain. The company is studying a depression drug - DOV 216,303 - in a Phase I trial, and has other products at various development states in depression, panic disorder, stress urinary incontinence, attention deficit disorder and Parkinson's disease.