Late Breakers

Neurology Alert is pleased to introduce our new column "Late Breakers." In an effort to stay up to date, Neurology Alert will be including short reviews of current therapeutics in both early and pivotal stage development. Different from our usual format, the sources of our information for "Late Breakers" will be medical scientific meetings and company news releases.

Vagal nerve stimulation (VNS) fails in depression. VNS has been a valuable adjunct to epilepsy treatment over the past 6 years. In an effort to expand its vagal nerve neuromodulatory franchise, Cyberonics Inc undertook a study of VNS in depression. Observational data from the epileptic population were notable for a mood enhancing response from VNS. A 60 nonepileptic depression patient pilot study (D-01) showed a 45% 1- year response rate. Response rate was defined as a > 50% reduction in Hamilton Depression Rating Scale (HDRS). Overall remission in depression at 1 year was achieved in 27% of patients (HDRS < 10). Benefit was proportional to the severity of the depression but no efficacy was seen in the most severe patients who had failed both ³ 6 medications (Sackeim HA, et al. Neuropsychopharmacology. 2001;25:713-728). A pivotal randomized, double-blind, placebo-controlled crossover designed study (D-02) was undertaken in 235 patients. The 12-week acute data showed no statistical significant difference between placebo and the group receiving VNS. Unfortunately, the study protocol allowed too much discretion on the part of treating physicians and 52% of patients ended up receiving inadequate stimulation doses. Cyberonics maintains that the study failed rather than VNS for depression (Cyberonics news release). A new pivotal study is currently being planned. FDA supplemental approval is still possible. VNS is a well-tolerated mode of therapy and, as with epilepsy, given where polypharmacy is often required but poorly tolerated, it would a valuable addition to depression treatment.

An Alzheimer vaccine trial is stopped. Elan Corp and Wyeth-Ayerst Laboratories suspended all trials of the drug AN-1792 after 15 patients in the Phase IIa trial developed encephalitis. AN-1792 is a b-amyloid 42 amino acid vaccine that had already been tested safely in 360 patients during preclinical and Phase I trials. Data published in Nature 1999 showed that Ab-42 injected into transgenic (PDAPP) mice could both prevent and reduce the formation of amyloid plaque. Details of the cases of these 15 patients have not yet been released (Elan news release).

A new sleep drug with modified release efficacy. Neurocrine Biosciences Inc announced positive results of NBI-34060 in a Phase II study of 47 patients with primary insomnia and sleep maintenance complaints. The primary end point was sleep efficiency, defined as total sleep time divided by 8 hours and measured objectively by polysomnography. NBI-34060 demonstrated 87-88.5% sleep efficiency compared to 84% in the placebo group (P < 0.002). An immediate release preparation is ion Phase III testing for sleep initiation. NBI-34060 is a specific GABA-A agonist, which is thought to be more potent than zolpidem (Ambien) and zaleplon (Sonata). The modified release formulation allows more flexibility in dosing particularly elderly patients with problems of sleep maintenance (Neurocrine news release). —Jeffrey Reich

Dr. Reich, Assistant Professor of Neurology, New York Presbyterian Hospital-Cornell Campus, is Assistant Editor of Neurology Alert.