SANTA CLARA, Calif., May 22 /PRNewswire-FirstCall/ -- XenoPort, Inc. announced today preliminary top-line results of a Phase 2a clinical trial indicating that single doses of XP19986 were well tolerated and produced statistically significant reductions in the number of reflux episodes in patients with gastroesophageal reflux disease, or GERD.
The randomized, double-blind, placebo-controlled, cross-over trial enrolled 35 patients in three sites in the United States. Enrolled patients had a history of GERD symptoms at least three times per week, and met a screening criterion of 20 or more reflux events in the two hours following a reflux-provoking meal. Reflux events were monitored using a pH/impedance probe placed in the esophagus. Each patient who met the entry criteria received single doses of XP19986 or placebo in separate test periods with four to seven days between testing periods. On the testing days, dosing occurred one hour after probe placement. Reflux-provoking meals were consumed at two hours and six hours after dosing. Reflux events were monitored for 12 hours. In addition, blood samples were taken at regular time intervals for the purpose of pharmacokinetic assessment.
The dose of XP19986 administered to the first cohort of 12 patients was 10 mg, and subsequent cohorts received doses of either 20 or 40 mg. XP19986 was formulated in a prototype sustained-release capsule that had previously been tested in healthy subjects.
The pre-specified primary endpoint for the clinical trial was the total number of reflux events over the 12-hour monitoring period following the dose of XP19986 or placebo. Analysis was performed on data from the combined dose groups and on each individual dosage group. The median number of reflux events during placebo treatment for the combined 10, 20 and 40 mg groups was 51.0 (n=35), and the median reduction in reflux events after XP19986 treatment compared to placebo treatment in these patients was -7.0 (p=0.034). For the individual 10, 20 and 40 mg dosage groups, the median number of reflux events during placebo treatment was 79.0 (n=12), 52.0 (n=12) and 34.0 (n=11), respectively, and the median reduction in reflux events after XP19986 treatment compared to placebo treatment in these patients was -2.0 (p=0.458), -11.5 (p=0.210) and -10.0 (p=0.051), respectively. In the 40 mg dose group, 9 of 11 patients had fewer reflux events after XP19986 treatment than after placebo treatment.
XP19986 was well tolerated at all dose levels with few reported adverse events. Preliminary pharmacokinetic results were consistent with those previously observed in healthy subjects taking XP19986. Based on the tolerability of XP19986 at single doses up to and including 40 mg, pursuant to the study protocol, 60 mg of XP19986 and placebo are being tested in a final cohort of GERD patients.
“GERD is a common disorder affecting the quality of life of many patients I see in my practice. Untreated GERD can have serious medical consequences, and existing treatments do not fully meet the needs of all GERD patients,” said Donald Castell, M.D., Professor of Medicine in the Division of Gastroenterology and Hepatology, Director of the Esophageal Disorders Program at the Medical University of South Carolina and a principal investigator of this study. “This initial investigation of XP19986 in a small number of GERD patients is encouraging, both in terms of the efficacy in reducing reflux and the favorable tolerability of XP19986.”
Ronald W. Barrett, Ph.D., XenoPort’s chief executive officer, added, “We are pleased that this exploratory study of XP19986 demonstrated a reduction in reflux events in GERD patients and yielded information to guide the selection of doses for future studies. When coupled with our previous Phase 1 trials in healthy subjects, we are particularly encouraged by the tolerability of single doses of XP19986. We plan to use the information from this Phase 2a trial to choose one or more XP19986 dosage strengths/formulations to test in multiple-dose studies. A published study of racemic baclofen in GERD patients has indicated that multiple doses given daily for 30 days was even more effective in reducing reflux and symptoms than a single day of multiple doses. We will provide an update on the design and timing of our next studies when detailed analysis of the current study, including an examination of the exposure-response relationship and an analysis of the data from the 60 mg dose cohort, has been completed.”
About XP19986
XP19986 is designed to overcome the deficiencies of baclofen, which is a generic drug approved for the treatment of spasticity. Baclofen is a racemic drug (a 50:50 mixture of R- and S-isomers). Studies conducted by third parties have shown that the beneficial therapeutic properties of baclofen are attributable to the R-isomer of baclofen only. Baclofen has a short half-life in blood after oral dosing, which necessitates frequent daily dosing. Absorption of baclofen in the colon is limited, which has prevented the development of a sustained-release formulation that could improve therapy.
XP19986 is a new chemical entity that is a Transported Prodrug of R-baclofen. XP19986 is designed to engage natural nutrient transport mechanisms found on intestinal cell membranes, thereby gaining efficient entrance into the bloodstream. XP19986 is then rapidly converted to R-baclofen by high-capacity enzymes. In addition to R-baclofen, the metabolic breakdown products of XP19986 are natural substances with favorable safety characteristics.
Phase 1 clinical trial testing of our prototype sustained-release formulation of XP19986 demonstrated a delayed time to maximal R-baclofen blood concentrations and a long terminal half-life, consistent with the requirements for twice-a-day dosing.
In addition to GERD, XenoPort intends to develop XP19986 as a potential treatment for spasticity. Spasticity is a widespread and debilitating condition that is associated with some common neurological disorders, such as multiple sclerosis, stroke and cerebral palsy. According to the IMS National Prescription Audit Report, for the 12 months ended November 30, 2005, there were approximately 3.3 million prescriptions written for baclofen in the United States.
About GERD and Baclofen
GERD is a digestive system disorder characterized by the frequent, undesirable passage of stomach contents into the esophagus that results in discomfort and potential damage to the lining of the esophagus. More than $10 billion is spent worldwide each year on GERD and heartburn medications, and approximately 7% of the global population experiences GERD symptoms daily. Conventional treatment for GERD includes medications that suppress stomach acid, such as proton pump inhibitors and H2-receptor antagonists, as well as over-the-counter antacids. However, these treatments are not effective in all patients, and there is a subset of patients who suffer from GERD symptoms due to reflux of stomach contents that are not acidic.
Baclofen has recently been the subject of clinical trials demonstrating that it may be effective in treating GERD. Unlike acid suppressing agents, baclofen exerts its effects on the function of the lower esophageal sphincter. Baclofen reduces the frequency of transient lower esophageal sphincter relaxations and, therefore, passage of gastric contents into the esophagus. We believe that the favorable pharmacokinetics of XP19986 may make it well suited for treatment of GERD, either as monotherapy or in combination with an acid suppressing agent.
About XenoPort
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’s most advanced product candidate, XP13512, has commenced a Phase 3 clinical program for the treatment of Restless Legs Syndrome, and has successfully completed a Phase 2a clinical trial for the management of post-herpetic neuralgia. XenoPort has also completed two Phase 1 clinical trials of XP19986, and reported preliminary positive results of a Phase 2a clinical trial of XP19986 in GERD patients.
To learn more about XenoPort, please visit the web site at www.XenoPort.com.
Forward-Looking Statements
This press release contains “forward-looking” statements, including, without limitation, all statements related to our future clinical development program for XP19986 and the timing thereof; the therapeutic and commercial potential of XP13512 and XP19986; future clinical development plans; and our future clinical trials. 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 “believes,” “anticipates,” “plans,” “expects,” “will,” “intends,” “potential” 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, the ability of the company to successfully conduct the clinical trials for XP13512 and XP19986; the uncertainty of the FDA approval process and other regulatory requirements; and the therapeutic and commercial value of the company’s compounds. These and other risk factors are discussed under the heading “Risk Factors” in our Quarterly Report on Form 10-Q for the quarter ended March 31, 2006, filed with the Securities and Exchange Commission on May 11, 2006. 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 U.S. trademarks of XenoPort, Inc.
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XenoPort, Inc.
CONTACT: Jackie Cossmon of XenoPort, Inc., +1-408-616-7220, orir@XenoPort.com
Web site: http://www.xenoport.com//
