Healthcare Industry News: Restless Legs Syndrome
News Release - October 22, 2006
XenoPort Announces Positive Results From XP19986 Phase 2a Trial in Patients with Gastroesophageal Reflux DiseaseData Presented at the American College of Gastroenterology Meeting
SANTA CLARA, Calif., Oct. 22 (HSMN NewsFeed) -- XenoPort, Inc. (Nasdaq: XNPT ) announced that additional data from the company's Phase 2a single-dose clinical trial of XP19986 in patients with gastroesophageal reflux disease, or GERD, was presented today in a poster presentation at the American College of Gastroenterology (ACG) meeting in Las Vegas, Nevada. The lead author is Donald O. Castell, M.D., Professor of Medicine in the Division of Gastroenterology and Hepatology, and Director of the Esophageal Disorders Program at the Medical University of South Carolina. The data presented indicate that single doses of XP19986 were well tolerated and produced statistically significant reductions in the number of reflux episodes and reflux-associated heartburn symptoms.
"The exciting results from this initial investigation indicate that XP19986 can reduce reflux and, therefore, has the potential to provide a much- needed addition to the treatment armamentarium for GERD patients. Importantly, the reduction in both reflux and heartburn associated with reflux was achieved at doses that had very few reported side effects," said Dr. Castell. "Based on these early findings, XP19986 could be especially helpful to the large number of GERD patients who experience inadequate relief of symptoms with current treatments."
The poster presentation reported results from a single-dose, randomized, double-blind, placebo-controlled, cross-over clinical trial conducted at 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 was monitored using a pH/impedance probe placed in the esophagus. The pH/impedance probe allows the monitoring of both acid and non-acid reflux episodes. 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, and patients were required to lie on their right side for two hours after each meal. Reflux was monitored continually for 12 hours. Patients also recorded when they experienced heartburn or regurgitation symptoms. In addition, blood samples were taken at regular time intervals for the purpose of pharmacokinetic assessment. Separate cohorts of patients were administered 10, 20, 40 or 60 mg single doses of XP19986, which was formulated in a prototype sustained-release capsule that had been tested previously in healthy subjects.
The pre-specified primary endpoint for the clinical trial was the total number of reflux episodes over the 12-hour monitoring period following the dose of XP19986 or placebo. Acid and non-acid reflux were analyzed as secondary endpoints. Reflux episodes by hour and the number of heartburn and regurgitation events were also analyzed.
The median number of total reflux episodes over 12 hours after placebo treatment for the combined dose groups was 50.5 (N=44). The median change in total reflux episodes after XP19986 treatment compared to placebo treatment was -9.5 (p=0.0050).
XP19986 treatment, compared to placebo, was also associated with a statistically significant reduction in the number of acid reflux episodes during the 12-hour monitoring period. The median number of acid reflux episodes during placebo treatment for the combined dose groups was 39.0, with a median reduction of -9.5 (p=0.0027). Further evaluation of individual dose groups showed that XP19986 dosing was associated with statistically significant reductions in acid reflux episodes in both the 40 mg (p=0.0498) and 60 mg (p=0.0039) dose groups, with 18 of 20 patients in these two dose groups having fewer acid reflux episodes in the 12 hours after XP19986 treatment compared to placebo treatment.
Analysis of the combined doses for reflux occurring during each hour interval after dosing indicated that the number of reflux episodes increased after each meal, as expected. XP19986 treatment resulted in a reduction, compared to placebo, of reflux episodes at all periods beyond the 3rd hour, with reductions reaching statistical significance in the 4th, 8th, 9th and 10th hours.
Single-dose treatment with XP19986 resulted in a statistically significant reduction, compared with placebo, in the number of heartburn events that were associated with a reflux episode over the 12-hour monitoring period (p=0.0294 for the combined dose groups).
XP19986 was well tolerated at all dose levels with few reported adverse events. Pharmacokinetic results indicated that exposure to R-baclofen was proportional to dose with an extended length of exposure, similar to that observed previously in Phase 1 clinical trials in healthy subjects.
Ronald W. Barrett, Ph.D., XenoPort's chief executive officer, stated, "The demonstration that single doses of XP19986 reduce reflux and heartburn associated with reflux in GERD patients is an important step in the development of XP19986. The study also confirmed that XP19986 can provide a pharmacokinetic profile suitable for twice-a-day dosing and is well tolerated at the single doses that impact reflux. We look forward to advancing the development of XP19986 with the goal of providing a new treatment option for GERD patients."
XP19986 is a patented new chemical entity that is a Transported Prodrug of R-baclofen. XP19986 is designed to overcome the short half-life and poor absorptive properties that make racemic baclofen suboptimal for spasticity treatment (a currently approved indication of baclofen) and unsuitable as a practical treatment for GERD symptoms.
Phase 1 clinical trials of the 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. Phase 2a clinical trial results, reported today at the ACG meeting, demonstrated that single doses of XP19986 were well tolerated and produced statistically significant reductions in the number of reflux episodes and reflux-associated heartburn symptoms in patients with GERD.
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 investigator-sponsored clinical trials demonstrating that it may be effective in reducing gastroesophageal reflux. 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 the treatment of GERD, either as monotherapy or in combination with an acid suppressing agent.
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 has reported 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.
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; the suitability of XP19986 as a treatment for GERD; 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 June 30, 2006, filed with the Securities and Exchange Commission on August 10, 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.
NOTE: XenoPort is a trademark of XenoPort, Inc.
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