Traumatic Brain Injury

January 3, 2005

GlaxoSmithKline reported results from a study with Requip (ropinirole), an approved non-ergoline dopamine agonist being investigated for the treatment of Restless Legs Syndrome (RLS). The placebo-controlled study enrolled 267 subjects with moderate-to-severe primary RLS. Results demonstrated that that Requip Tablets effectively treated the symptoms of primary Restless Legs Syndrome (RLS) as assessed by improvements in symptoms, over 12 weeks. Improvements were significantly better for Requip than placebo on the IRLS Scale (-11.2 vs. -8.7; p = 0.0197). In addition, the drug showed significant improvements in sleep and quality of life in RLS patients taking Requip versus placebo. The primary endpoint was the change in International RLS Rating Scale (IRLS Scale) score at week 12. On the CGI-I scale, 36.6% of subjects taking Requip (48/131) responded "much improved" or "very much improved" after one week compared with 16.4% (22/134) of subjects taking placebo. Subjects were randomized to Requip (0.25-4.0 mg/day) or placebo, 1-3 hours before bedtime. Full results were reported in the journal Movement Disorders. Requip is currently under FDA review for the treatment of the signs and symptoms of primary RLS.

Pharmos reported negative results from a phase III trial with dexanabinol (HU-211), a NMDA-receptor antagonist for the treatment of severe traumatic brain injury (TBI). The trial was one of the largest ever undertaken for the treatment of TBI. The pivotal, double-blind, randomized, placebo-controlled trial enrolled 861 subjects and was conducted in 86 trauma centers in European, Israeli, Australian and U.S. Results showed that dexanabinol did not demonstrate efficacy as measured by the primary clinical outcome endpoint, the Extended Glasgow Outcome Scale (GOSE). The study, however, did demonstrate an excellent safety profile with no evidence of excess side effects in the dexanabinol-treated patients. The primary endpoint was defined as a statistically significant increase in the number of dexanabinol-treated patients achieving a favorable outcome when compared to the placebo group at six months. To be enrolled, subjects must have sustained a severe brain injury as judged by both a Glasgow Coma Score between 4 and 8 and by a CT scan showing brain parenchymal damage. Subjects must have been administered a single dose of placebo or 150 mg of dexanabinol within 6 hours of injury. The company stated they will likely discontinue dexanabinol for TBI but plans to continue developing the drug for cognitive impairment in cardiac surgery. Dexanabinol is under license from the Hebrew University of Jerusalem as part of a series of tricyclic dextrocannabinoids.

July 5, 2004

Novo Nordisk has announced positive results of their phase IIb study of NovoSeven for the treatment of intracerebral hemorrhage (ICH). NovoSeven is currently approved as a treatment for acute bleeding in hemophilia. Results have shown that the drug led to a significant reduction in hematoma growth, compared to placebo, and significantly improved neurological and functional outcomes following an ICH incident. The double-blind, dose-response study enrolled a total of 400 subjects in 20 countries; subjects with spontaneous ICH confirmed by CT scan within three hours of symptom onset randomized to receive either NovoSeven or placebo, in addition to standard therapy. Follow-up CT scans, performed at 24 and 72 hours, found that NovoSeven significantly and dose-dependently reduced hematoma expansion, and observations at 15 and 90 days found significant improvement in severity score on neurological function tests in the NovoSeven group. Novo Nordisk announced plans to file supplementary regulatory submissions based upon this data.