GSK/XenoPort Next-Generation RLS Drug Shows Efficacy In Phase III
This article was originally published in The Pink Sheet Daily
Executive Summary
NDA filing for the non-dopaminergic candidate is on track for third quarter.
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GlaxoSmithKline and XenoPort's non-dopaminergic Restless Legs Syndrome candidate, GSK1838262, maintained efficacy over nine months of treatment according to top-line results from a Phase III trial the firms released Jan. 15. The positive results put the company on track to file an NDA in the third quarter, a timeline GSK announced in December (1 (Also see "GSK Plans Next-Generation Restless Legs Treatment Filing In Q3 2008" - Pink Sheet, 13 Dec, 2007.)). "Our study design and endpoints were defined after extensive consultation with the FDA, and we therefore believe that these positive results will be a supportive part of our NDA," XenoPort CEO Ronald W. Barrett said during a same-day conference call. The multi-center, randomized, placebo-controlled clinical trial enrolled 327 patients diagnosed with moderate-to-severe RLS. The trial included two phases. In the first single-blind phase, all patients were administered 1,200 mg of the study drug at approximately 5 p.m. for 24 weeks. The study assessed treatment response at the end of the single-blind phase of the trial using three criteria: a decrease in total International RLS rating scale score of six or more points compared to baseline, a decrease in IRLS score to less than 15 and assessment of "much improved" or "very much improved" on the Investigator Clinical Global Impression of Improvement. Responders had to be stabilized on 1,200 mg of treatment for at least the last month of the 24-week treatment period. Following the single-blind phase of the study, responders, of which there were 194, entered a 12-week, double-blind phase in which patients were randomized to receive 600 mg of GSK1838262 or placebo during the course of treatment. The primary endpoint of the trial was the proportion of RLS patients who relapsed or had their RLS symptoms worsen during the 12-week, double-blind treatment period. The data showed that a statistically significant lower proportion of relapses occurred in the treatment group (23 percent) versus the placebo arm (9 percent) during the double-blind phase. "We are particularly pleased with these results in the face of the stringent relapse criteria that were arrived at with the FDA," Barrett noted. The most common reported adverse events among treated patients were somnolence and dizziness. There was one death, determined as unrelated to treatment, and there were five other serious adverse events, only one of which, a seizure, was determined possibly to be related to the drug. GSK acquired the rights to the gabepentin prodrug for RLS and neuropathic pain last year through a development deal with XenoPort valued at up to $640 million (2 (Also see "GSK Extends RLS Franchise With Gabapentin Prodrug Through XenoPort Deal" - Pink Sheet, 8 Feb, 2007.)). The companies could face challenges, however, in positioning the drug to compete against a low-priced generic version of GSK's Requip (ropinirole), slated to lose exclusivity in May. Nonetheless, the firms have maintained that opportunities exist for improved RLS drugs on the market. "Chronic use of dopamine agonists has been associated with things like augmentation and compulsive behavior so we think that ['262], because it works by a different mechanism and, at least for the foreseeable future, will be the only approved non-dopaminergic treatment for Restless Legs Syndrome, will be attractive to physicians and patients from a safety side," Barrett said during the call. GSK also has announced plans to initiate a pivotal Phase III dose ranging efficacy study and safety studies evaluating '262 for the treatment of migraine prophylaxis in the second half of 2008. The firms are studying the drug to treat neuropathic pain as well. -Jessica Merrill ([email protected]) |