West Coast Editor

Aiming for a new drug application filing at the end of next year, Neurocrine Biosciences Inc. unveiled an eye-opening Phase III trial program that will include about 3,500 patients testing two formulations of the company’s insomnia drug.

San Diego-based Neurocrine said it is starting three pivotal Phase III trials of the immediate-release form of NBI-34060 (having begun the first Phase III study late last year), and will conduct a total of five for that formulation. The company also expects to conduct three Phase III trials evaluating the modified-release version of the same drug.

Although details about the program previously were not disclosed, Paul Hawran, chief financial officer of Neurocrine, said, “We’ve always intended to have a strong Phase III program, and we always planned to include approximately 3,500 patients.”

The company has begun a randomized, double-blind, placebo-controlled, outpatient, 60-center Phase III trial to assess the long-term safety and efficacy over six months of two dose levels of immediate-release NBI-34060 in patients with chronic insomnia. Its primary endpoint is latency to sleep onset, as measured by outcomes reported by patients. Another, a parallel-group trial of the same drug has begun at 20 centers in adults with transient insomnia. The primary endpoint is latency to persistent sleep, as measured by polysomnography.

The fourth Phase III trial, also at 20 centers, is slated to start next month. Like the other trial, this randomized, double-blind, placebo-controlled, parallel-group study will evaluate the safety and efficacy of two doses of immediate-release NBI-34060 in adults with chronic insomnia. This in-patient/outpatient study will have latency to persistent sleep as its primary endpoint, measured by polysomnography.

In all three trials, the secondary endpoints are sleep quality and next-day effects.

NBI-34060 is a non-benzodiazepine compound that acts against insomnia through a specific site of the GABA-A receptor. Neurocrine’s first Phase III trial of the immediate release form in 500 patients began in November at 40 sites. (See BioWorld Today, Nov. 19, 2001.)

Henry Pan, chief scientific officer of Neurocrine, said last year’s trial has enrolled 200 patients so far. He said the company is striving to distinguish its drug by showing value for adult and elderly patients with varying types of sleep trouble, including those who wake in the middle of the night and need a drug that will be out of their systems by morning.

“This is a huge market with so many different patients with different types of insomnia,” he said. “How do you find the right solution? It requires a bit of ingenuity, but our program will definitely cover the spectrum.”

Currently available medications are indicated only for 7 to 10 days of treatment, Pan noted, and “when you have insomnia, you have it for a long period of time some patients for their entire lives.”

The two marketed insomnia therapies are Wyeth-Ayerst Laboratories Inc.’s Sonata (zaleplon), and Sanofi-Synthelabo SA’s Ambien (zolpidem), both of which also stay in the patient’s body for periods longer than optimal in the case of dosages taken during the night, Pan said.

Neurocrine’s program with NBI-34060, which includes year-long Phase III trials as well as follow-up studies, is designed to prove it’s safe and effective not only for people who need dosing immediately upon waking at night, but for those who must use it for “months and months,” Pan said.

Along with the four Phase III studies with immediate release NBI-34060, another is planned to begin shortly, and three Phase III trials with the modified-release form (for sleep maintenance) will start later this year, Pan told BioWorld Today.

Neurocrine’s stock (NASDAQ:NBIX) closed Tuesday at $38.50, up 30 cents.