Washington Editor

Neurocrine Biosciences Inc. released favorable data from two long-term Phase III studies proving that its insomnia candidate, indiplon, remains effective for at least three months and is associated with quality-of-life improvements for its users.

The two trials, referred to as "RESTFUL" and "SLEEP," conclude an 11-trial Phase III program sponsored by San Diego-based Neurocrine and its partner, New York-based Pfizer Inc. The program database includes 5,000 patients and confirms that indiplon can improve sleep in patients with transient and chronic insomnia, the company said.

Neurocrine's stock (NASDAQ:NBIX) moved up 72 cents Wednesday to close at $60.35.

Gary Lyons, Neurocrine's president and CEO, told BioWorld Today the partners expect to file one new drug application for the immediate-release formulation and a second NDA for the modified-release version sometime in mid-2004. He said the firms plan to seek a broad label that would include sleep initiation, middle-of-the-night insomnia, sleep-maintenance insomnia and long-term (at least three months) treatment.

Discovered in the laboratories of Madison, N.J.-based Wyeth and later purchased by Neurocrine and Pfizer, indiplon is a non-benzodiazapine agent that acts on a specific site of the GABA-A receptor. The compound has been shown to bind selectively to the specific subtype of GABA-A receptors within the brain believed to be responsible for promoting sleep.

During the Wells Fargo Securities Healthcare Conference in New York Wednesday, Lyons presented data from RESTFUL, a study of the immediate-release formulation, and SLEEP, a study designed to measure the safety and effectiveness of the modified-release formula of the candidate.

"These were probably the most important studies we did because we believe long-term use will expand the market," Lyons said. "So rather than prescribing this for one week, physicians can prescribe it for 30 days on an ongoing basis. Obviously its sales potential is much greater."

Some analysts say indiplon is a potential blockbuster, Lyons said.

He believes indiplon will provide chronic insomniacs with a better option for treatment, adding that its primary competitor will be Ambien (zolpidem tartrate), from Paris-based Sanofi-Synthelabo SA, a product specific to short-term sleep problems.

"[RESTFUL and SLEEP] are the first trials to show that the drug continues to work over time. Most people had thought it would work as a seven- to 10-day treatment, like Ambien," Lyons said. "But these trials have shown that the efficacy is as good at the end of three months as it is on the first night."

Furthermore, indiplon does not cause a next-day hangover or other impairment in the morning, Lyons said.

Preliminary results from SLEEP demonstrated that patients who took indiplon modified release at either the 20-mg or 30-mg nightly dose achieved rapid sleep onset, maintained high-quality sleep throughout the night and showed improvement in quality-of-life endpoints. Indiplon treatment demonstrated a highly statistically significant improvement in sleep for all primary and secondary endpoints, compared to placebo, for both doses and all time points (p<0.0001). Patients on both doses of indiplon reported an increase of up to 75 minutes, compared to placebo, in total sleep time, the primary endpoint for the study, and up to 90 minutes improvement over baseline, the company said.

SLEEP was a 740-patient, randomized, double-blind, placebo-controlled, parallel-group, multicenter, outpatient trial. Meanwhile, RESTFUL, set up similarly, studied 700 patients over three months to assess the efficacy and safety of nightly administration of two doses of indiplon immediate release (10 mg and 20 mg), relative to placebo.

Results showed that with either of the two dose levels of indiplon immediate release, patients achieved rapid sleep onset and slept longer with minimal sleep disturbances. Efficacy results with indiplon immediate-release 10-mg and 20-mg doses demonstrated a highly statistically significant improvement in patient-reported latency to sleep onset, or the time it took patients to fall asleep (p<0.001 to p<0.0001) at all time points, as compared to placebo, a 30 percent improvement over placebo and more than 27 minutes over baseline, the company said.

Recently, Neurocrine agreed to pay $95 million in cash and stock to purchase Wyeth's interest in indiplon. (See BioWorld Today, March 1, 2004.)

Indiplon initially was the subject of a 1998 licensing agreement between Wyeth and DOV Pharmaceutical Inc., of Hackensack, N.J. DOV later licensed the candidate to Neurocrine, which entered a $400 million deal with Pfizer to take it to market. (See BioWorld Today, July 10, 1998, and Dec. 20, 2002.)