SANTA CLARA, Calif.--(BUSINESS WIRE)--XenoPort, Inc. (Nasdaq:XNPT) announced today preliminary top-line results from a Phase 2b clinical trial of arbaclofen placarbil (also known as AP) as adjunctive therapy in patients with gastroesophageal reflux disease (GERD) who do not experience complete relief of GERD symptoms while being treated with proton pump inhibitors (PPI). In this study, subjects who experienced GERD symptoms despite PPI therapy were randomized to receive a PPI plus placebo, or a PPI plus one of four AP dose regimens (20 mg or 40 mg of AP dosed once daily (QD), or 20 mg or 30 mg of AP, dosed twice daily (BID)), for six weeks. None of the AP doses showed statistically significant improvements over placebo in the analysis of the primary endpoint. Analyses of key secondary endpoints did not yield consistent results when AP doses were compared to placebo.
Ronald W. Barrett, Ph.D., XenoPort's chief executive officer, stated, "We are disappointed that AP failed to demonstrate clear efficacy over placebo in this trial. While we will continue to analyze the data, at this time, we do not believe the efficacy results of this study warrant our investment in further development for AP in GERD. We believe the AP safety profile observed in this study continues to support our planned Phase 3 development program for AP in patients with spasticity."
The randomized, double-blind, placebo-controlled Phase 2b clinical trial was conducted at 58 sites in the United States and Canada. The trial included a run-in period of up to four weeks whereby GERD patients with a history of incomplete response to a PPI were monitored while on PPI therapy. Subjects (n=460) who continued to experience four or more heartburn events over at least three days during baseline assessment in the third week of the run-in period, and who met other eligibility requirements, were randomized into a six-week double-blind phase of the study. Subjects received PPI therapy plus placebo, or PPI plus 20 mg QD, 40 mg QD, 20 mg BID or 30 mg BID of AP. The six-week treatment period included an up-titration period, and at the end of six weeks, subjects were tapered off treatment.
The primary efficacy endpoint was percent change from baseline in heartburn events per week with the primary analysis evaluating percent change from baseline in heartburn events at week six. Percent change in weekly heartburn events was analyzed using a repeated measures ANCOVA model. At week six, subjects in the placebo group showed a mean percent reduction in heartburn events of 68%. Although there were trends for improvement over placebo in the AP dose groups, none of the comparisons to placebo reached statistical significance.
AP was safe and generally well tolerated at all dose levels. There were six treatment emergent serious adverse events in five subjects, including one death that was due to arteriosclerosis, but none were assessed as related to AP. The most common adverse events in the combined AP dose groups were somnolence, dizziness and nausea that occurred in 16%, 13% and 11% of subjects, respectively, compared to 2%, 3% and 6% of subjects in the placebo group. Most reported adverse events were mild or moderate in severity. Withdrawals due to adverse events were 6% in subjects receiving placebo and 16% in subjects receiving AP. The most common reasons for withdrawal were nausea, somnolence, dizziness and headache, none of which exceeded 5%.
Conference Call and Webcast Information
XenoPort will host a conference call at 9:00 a.m. Eastern Time today to discuss the Phase 2b clinical trial results and plans for AP development. To access the conference call via the Internet, go to www.XenoPort.com. To access the live conference call via phone, dial 1-888-275-3514. International callers may access the live call by dialing 706-679-1417. The reference number to enter the call is 53835577.
The replay of the conference call may be accessed after 12:00 p.m. Eastern Time today via the Internet, at www.XenoPort.com, or via phone at 1-800-642-1687 for domestic callers, or 706-645-9291 for international callers. The reference number to enter the replay of the call is 53835577. Dial-in access to the replay of the call will be available for approximately one week, and the Internet replay of the call will be available for approximately one month following the live call.
About Arbaclofen Placarbil (AP)
XenoPort is currently developing AP as a potential treatment for patients with spasticity. AP is a patented new chemical entity that is a Transported Prodrug of R-baclofen designed to engage natural nutrient transport mechanisms found on intestinal cell membranes, thereby gaining efficient entrance into the bloodstream. AP is then rapidly converted by high-capacity enzymes to the parent compound and natural substances with favorable safety characteristics. R-baclofen is an agonist of the target known as gamma amino-butyric acid(B), or GABA(B), receptor. Baclofen, which is a mixture of the R- and S-isomers, is an approved treatment for spasticity that is administered three or four times a day.
XenoPort has completed a successful Phase 2 clinical trial of AP in patients with spasticity due to spinal cord injury. AP treatment was associated with statistically significant differences from placebo at all time points in the 20 mg BID and 30 mg BID dose cohorts of AP. AP was safe and well tolerated at all dose levels.
XenoPort, Inc. is a biopharmaceutical company focused on developing a portfolio of internally discovered product candidates that utilize the body's natural nutrient transport mechanisms to improve the therapeutic benefits of existing drugs. XenoPort is developing its lead product candidate in collaboration with Astellas Pharma Inc. and GlaxoSmithKline. XenoPort's product candidates are being studied for the potential treatment of restless legs syndrome, neuropathic pain, spasticity and Parkinson's disease. To learn more about XenoPort, please visit the web site at www.XenoPort.com.