XenoPort Reports Positive Results from a Phase 2 Trial of Arbaclofen Placarbil in Spinal Cord Injury Patients with Spasticity
SANTA CLARA, Calif.- XenoPort, Inc. announced today positive preliminary results from a Phase 2 clinical trial of arbaclofen placarbil (AP), also known as XP19986, for the treatment of patients with spasticity due to spinal cord injury (SCI). Doses of 20 and 30 mg of AP, given twice daily (BID), demonstrated statistically significant improvements compared to placebo for the primary endpoint of the study. AP was well tolerated during the trial.
“Currently available medications for treating spasticity are often limited by their short duration of action and significant central nervous system side effects,” said David A. Stamler, M.D., XenoPort’s chief medical officer. “The efficacy and tolerability of AP that were observed in this trial was encouraging, and we believe that AP offers the potential to address important medical needs for SCI patients.”
This Phase 2 clinical trial was a randomized, double-blind, placebo-controlled, crossover study that enrolled 37 subjects at ten sites in the United States and Canada. Subjects with SCI between C-5 and T-12 discontinued spasticity therapy during a one-week washout period prior to a one-week placebo run-in period, at the end of which baseline assessments were conducted. Subjects had an Ashworth Scale score of at least 2 in one of six assessed muscle groups (hip abductors/adductors, knee flexors/extensors and ankle flexors/extensors) on the most affected leg. Subjects received either AP (10, 20 or 30 mg BID) or placebo in the first treatment segment of the two-segment crossover design. Each treatment segment included a titration period, followed by at least one week at the target dose, at which time efficacy assessments were performed (day 17 of each treatment segment). Each treatment segment also included a down-titration period, and there was a three-day washout between treatment segments.
The primary endpoint in this study was the difference in Ashworth Scale score during the placebo and AP treatment segments for the muscle group with the highest Ashworth Scale score at baseline. Ashworth Scale scores were determined by the investigator prior to dosing, and again two, four and six hours after the morning dose. The primary analysis used a repeated-measures analysis of variance model and included data from the 35 subjects who completed both treatment segments.
Mean maximum baseline Ashworth Scale scores were 3.2 (n=10), 3.1 (n=12) and 3.1 (n=13) for the 10, 20 and 30 mg BID AP dose cohorts, respectively. For the primary endpoint, the overall adjusted mean differences between placebo and AP over the six-hour assessment period for these cohorts were -0.17 (not significant), -0.60 (p=0.0059) and -0.88 (p=0.0007), respectively. AP treatment was associated with statistically significant differences from placebo at all time points in the 20 and 30 mg BID AP dose cohorts, indicating a treatment effect over the 12-hour dosing interval. In a secondary analysis, 20 and 30 mg BID of AP also showed a statistically significant difference from placebo in the average Ashworth Scale score for all six muscle groups.
AP was well tolerated at all dose levels. There were no withdrawals due to adverse events during the trial. The most commonly reported adverse events while on any AP dose were urinary tract infection (11% AP; 9% placebo), pain in extremity (8% AP; 0% placebo), insomnia (8% AP, 0% placebo) and nasopharyngitis (8% AP; 3% placebo). Side effects were generally mild to moderate in intensity. There were no drug-related serious adverse events.
“These results add to a growing body of evidence suggesting the efficacy and safety of AP in multiple indications,” said Ronald W. Barrett, Ph.D., XenoPort’s chief executive officer. “We believe AP offers the potential for a differentiated treatment of spasticity in SCI patients. We intend to seek guidance from regulatory authorities regarding future trial designs and safety database requirements for a clinical program leading to a new drug application for AP as a potential treatment of spasticity in SCI patients and possibly other spasticity populations.”
XenoPort will host a conference call at 9:00 a.m. Eastern Time today. 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 1-706-679-1417.
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 1-706-645-9291 for international callers. The reference number to enter the call and the replay of the call is 18012057.
AP (arbaclofen placarbil) is a Transported Prodrug of R-baclofen that is 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 R-baclofen and natural substances that have well-studied, favorable safety characteristics. The current sustained-release tablet formulation of AP could enable convenient once- or twice-daily dosing of subjects in future clinical trials.
R-baclofen is an agonist of the target known as gamma amino-butyric acid(B), or GABA(B), receptor. Racemic baclofen (a mixture of R and S isomers) has been approved for the treatment of spasticity and has been shown in clinical studies to have efficacy in a number of other therapeutic indications, including gastroesophageal reflux disease (GERD) and acute back spasms.
Spasticity is a debilitating condition that is associated with some common neurological disorders, such as multiple sclerosis, stroke and cerebral palsy, as well as spinal cord injury. Spasticity is a condition in which certain muscles are continuously contracted, interfering with movement or speech. According to data from Wolters Kluwer Health, Source® Pharmaceutical Audit Suite, for the 12 months ended December 31, 2008, there were approximately 7.0 million prescriptions written in the United States for the two most widely prescribed drugs for the treatment of spasticity, racemic baclofen and tizanidine.
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, XP13512, in collaboration with Astellas Pharma Inc. and GlaxoSmithKline. The Food and Drug Administration is currently reviewing the new drug application for this product candidate as a potential treatment for moderate-to-severe primary restless legs syndrome. XenoPort’s product candidates are also being studied for the potential treatment of GERD, migraine headaches, neuropathic pain, spasticity related to spinal cord injury, acute back spasms and Parkinson’s disease.
To learn more about XenoPort, please visit the Web site at www.XenoPort.com.
This press release contains “forward-looking” statements, including, without limitation, all statements related to our future clinical development program for AP and the timing thereof; the therapeutic and commercial potential of AP; the suitability of AP as a treatment for spasticity; and our future clinical trials and the timing thereof. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as “believe,” “could,” “intend,” “potential,” “suggesting” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon XenoPort’s current expectations. Forward-looking statements involve risks and uncertainties. XenoPort’s actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks related to the uncertain results of future clinical trials; XenoPort’s ability to successfully conduct future clinical trials for AP; the uncertainty of the FDA approval process and other regulatory requirements; and the uncertain therapeutic and commercial value of AP. These and other risk factors are discussed under the heading “Risk Factors” in XenoPort’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2009, filed with the Securities and Exchange Commission on May 7, 2009. XenoPort expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in the company’s expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.
XenoPort and Transported Prodrug are trademarks of XenoPort, Inc.
Jackie Cossmon, 408-616-7220