GSK, XenoPort disappointed with GSK1838262/XP13512 phase 2b study for migraine headaches

GlaxoSmithKline (NYSE:GSK) and XenoPort, Inc. (Nasdaq:XNPT) announced today that GSK1838262/XP13512 (gabapentin enacarbil) did not demonstrate a statistically significant improvement compared to placebo as a prophylactic treatment for migraine headaches. This phase 2b dose-ranging study evaluated the efficacy, safety and tolerability of GSK1838262 in adults diagnosed with migraine headache (with or without aura) according to the International Headache Society criteria.

“We are disappointed by the results of GSK1838262 in this clinical setting”

The 30-week, double-blind, placebo-controlled study randomized 526 patients to receive 1200, 1800, 2400 or 3000 mg/day of GSK1838262 or placebo, administered twice daily. The primary efficacy endpoint was the change from baseline in the number of migraine headache days during the last four weeks of treatment prior to taper. GSK1838262 did not demonstrate a statistically significant improvement over placebo on the primary endpoint. The failure of the study may be a consequence of the unexpectedly high placebo response rate observed.

The most common adverse event was dizziness, which was generally mild or moderate and did not lead to discontinuation in the majority of patients. Eight patients who received GSK1838262 and two who received placebo experienced serious adverse events during the trial. Of these events, two were deaths in patients receiving GSK1838262. One was due to bronchopneumonia and was assessed by the investigator as not related to the study drug. The second death resulted from an accidental overdose involving medications other than GSK1838262, but the relationship of this event to the study drug could not be established.

"We are disappointed by the results of GSK1838262 in this clinical setting," said Atul Pande, M.D., senior vice president, GlaxoSmithKline Neurosciences Medicines Development Center. "Unfortunately, migraine remains an often debilitating and undertreated condition. According to published studies, up to 40 percent of migraine sufferers could benefit from preventative therapies."

Ronald W. Barrett, Ph.D., chief executive officer of XenoPort, stated, "XenoPort is disappointed by these study results, especially the high placebo response rate, which may have impacted the ability of the trial to detect the potential benefit of GSK1838262 in patients with migraine headaches. We remain committed to working with our partners and regulatory authorities to make this product candidate available to patients with unmet medical needs."

Migraine is a chronic neurological disorder characterized by recurrent episodes of headache and associated symptoms. The condition affects approximately 30 million people in the U.S. The goals of preventative therapies, also called prophylactic treatment, are to reduce migraine attack frequency, prevent migraine-related disability and improve health-related quality of life.

GSK1838262 is a new chemical entity that is designed to provide dose proportional and sustained exposure of gabapentin by taking advantage of high-capacity transport mechanisms in the gastrointestinal tract. A New Drug Application for GSK1838262 for the treatment of moderate-to-severe primary restless legs syndrome (RLS) is being reviewed by the U.S. Food and Drug Administration (FDA).