By Mary Welch
Neurocrine Biosciences Inc. purchased an exclusive worldwide license from DOV Pharmaceuticals Inc. for rights to an insomnia drug, NBI-34060, that could be ready for Phase III trials as early as next year.
San Diego-based Neurocrine will be responsible for worldwide development and commercialization. The company agreed to a multi-million-dollar pact that includes an equity investment in DOV and milestone payments based upon certain clinical development and regulatory accomplishments. DOV also will receive royalties.
DOV Pharmaceuticals, of Fort Lee, N.J., licenses and develops drugs already in clinical trials. Currently, it is working on several therapeutics in the areas of the central nervous system and cardiovascular diseases.
The licensed compound works through activation of gamma-aminobutyric acid (GABA) receptors, which also are the targets of benzodiazepines, a class of sleep-inducing drugs on the market. GABA is an inhibitor of neurotransmission in the central nervous system.
NBI-34060 is considered a next-generation compound, chemically distinct from the benzodiazepines with an improved pharmacokinetic profile and receptor subtype selectivity.
NBI-34060 More Selective Than Benzodiazepines
Like the benzodiazepines, NBI-34060 increases the effects of the inhibitory neurotransmitter GABA. However, it binds to a subgroup of GABA receptors, which gives it a more selective action.
"By working on the receptor subtype and making it more selective, it reduces the side effects of benzodiazepine," said Bruce Campbell, vice president of development. "We call this a 'sleep promoter' because it is absorbed faster than current medication. It is absorbed within an hour of taking it and its half-life is a little over an hour."
What that means is that a person who can't fall asleep can take NBI-34060 and will be quickly snoozing under the compound's influence for about two hours when the body's natural sleep takes over. Because of this time frame, a person can even take NBI-34060 in the middle of the night.
"This does not change your sleep patterns over time. Phase I trials have shown it to be safe and effective. The most common noted effect was drowsiness, which is what it's supposed to do," said Campbell. "We intend to go into Phase Ib quickly and start a Phase II trial early in 1999. Phase III will start soon after that. We intend to develop this as rapidly as possible. We know quite a lot about it already."
Benzodiazepines have long been used to induce sleep, but they also result in several troubling side effects, including interaction with alcohol, development of rapid tolerance, potential for abuse and withdrawal symptoms, next-day hangover effects, and the impairment of psychomotor performance and memory.
Studies so far seem to indicate that NBI-34060 does not produce the next-day hangover effects, nor does it negatively interact with alcohol. It also doesn't give rise to rapid tolerance or amnesia.
The largest selling sleep inducer on the market is Ambien (zolpidem). Overall, the sleep-inducing market is between $500 million to $800 million. "We'll take anything in that market," Campbell said.
Ambien is marketed by G. D. Searle & Co., a Skokie, Ill., subsidiary of St. Louis-based Monsanto Co.
"The zolpidems do produce these negative side effects, and we believe NBI-34060 will get a lot of people who are afraid or nervous about taking sleeping inducers to try it. Because we're a sleep promoter, a lot of people who fear these products will not have a problem with ours. Elderly people are an example of this group," Campbell said.
Neurocrine Biosciences' stock (NASDAQ:NBIX) closed Thursday at $7.75, up $0.312. *