SANTA CLARA, Calif., Jan. 5 /PRNewswire-FirstCall/ -- XenoPort, Inc. announced today the results of a second Phase 1 clinical trial of XP19986, XenoPort's product candidate that is a potential treatment for gastroesophageal reflux disease, or GERD, and other disorders, demonstrating that escalating single doses of XP19986 resulted in predictable pharmacokinetics and that XP19986 was well tolerated at doses expected to be used in future clinical trials. The company also described its plans for conducting Phase 3 clinical trials of its most advanced product candidate, XP13512, as a treatment for restless legs syndrome, or RLS, following an End-of-Phase 2 meeting with the Food and Drug Administration, or FDA.
"These two developments are major milestones for our clinical product candidates," said Ronald W. Barrett, Ph.D., XenoPort's chief executive officer. "The favorable safety, pharmacokinetic and tolerability data observed in our second Phase 1 trial of XP19986 supports the further clinical development of XP19986, including our ongoing Phase 2a trial in GERD patients. Separately, our meeting with the FDA clarified the preclinical and clinical requirements for registration of XP13512 as a treatment for RLS. We believe that these two programs are now poised to make substantial development progress in 2006."
XP19986 Phase 1 Clinical Trial Results
A double-blind, placebo-controlled, escalating single-dose Phase 1 trial assessed safety, tolerability and pharmacokinetics of six oral dose levels (10, 20, 30, 40, 60 and 80 mg) of a prototype sustained-release formulation of XP19986 in healthy adult volunteers. For each dose level, an independent cohort of ten subjects (eight receiving XP19986 and two receiving placebo) was dosed. Subjects were monitored for adverse events. Blood and urine were sampled to determine pharmacokinetic profiles and bioavailability.
XP19986 is a Transported Prodrug of the R isomer of baclofen. Preliminary pharmacokinetic analysis indicated that XP19986 was absorbed from the gastrointestinal tract and rapidly converted to the R isomer of baclofen. Intact XP19986 in systemic blood was low compared to R-baclofen. Exposure to R-baclofen was dose-proportional across the entire dose range. The pharmacokinetic profile of XP19986 was consistent with the requirements for twice-a-day dosing. XP19986 was well tolerated with few reports of drug-related adverse effects at doses below 80 mg. At the 80 mg dose level, subjects receiving XP19986 reported a number of central nervous system side effects that have been previously reported for baclofen, with somnolence being the most prevalent (three of eight subjects). There were no serious adverse events in the trial.
"The ability to obtain dose-proportional and long-lasting levels of R-baclofen in healthy subjects offers the potential for twice-a-day dosing, an advantage over the currently marketed generic baclofen," stated Ken Cundy, Ph.D., XenoPort's senior vice president of preclinical development. "We look forward to assessing safety, tolerability and efficacy of XP19986 in GERD patients in our ongoing Phase 2a clinical trial, the results of which we expect in the first half of this year."
Overview of XP13512 Phase 3 Program in RLS
XenoPort also announced today that it has completed an End-of-Phase 2 meeting with the FDA regarding XP13512 as a treatment for RLS. As a result of the meeting, XenoPort has finalized plans for its Phase 3 clinical program for RLS.
The XP13512 Phase 3 clinical program is expected to encompass multiple U.S. trials, including two 12-week, randomized, double-blind, placebo-controlled trials designed to evaluate the efficacy and safety of 1200 mg of XP13512 administered once a day at approximately 5:00 PM. The first trial is anticipated to enroll approximately 200 patients and is expected to commence in the first half of this year, with a second trial of the same design expected to commence later this year. The co-primary outcome measures for these trials are defined to be the change from baseline in the International Restless Legs Scale score and the Clinical Global Impression of Improvement at the end of treatment. Secondary endpoints include onset of efficacy and subjective sleep, pain, mood and quality of life assessments. XenoPort expects that top-line data from its first Phase 3 trial will be available in the first half of 2007.
In addition, XenoPort plans to conduct a Phase 3 trial assessing the long-term efficacy of XP13512 using a placebo-controlled, "randomized withdrawal" design to evaluate relapse of RLS symptoms in XP13512-treated or placebo-treated patients who had previously achieved clinical improvement while taking 1200 mg of XP13512 for 24 weeks. XenoPort also plans to conduct an open-label safety trial of 1200 mg of XP13512 in RLS patients with duration of treatment extending up to 12 months. The results of this trial combined with those from other XP13512 clinical trials are intended to meet the International Committee for Harmonization, or ICH, guidelines for safety assessment. These trials are also expected to start later this year.
"We are very pleased to finalize our plans for the Phase 3 program for XP13512 as a potential treatment for RLS," stated Pierre Tran, M.D., XenoPort's chief medical officer. "Our Phase 2 program showed significant benefits of XP13512 over placebo in treating RLS. Our Phase 3 program is designed to confirm these findings while satisfying the requirements for an NDA submission and providing useful information regarding treatment of a variety of symptoms that impact the lives of RLS patients."
About XP13512
XP13512 is a Transported Prodrug of gabapentin, a drug that has been sold by Pfizer Inc as Neurontin since 1993 and is currently sold as a generic drug by a number of companies. XP13512 utilizes high-capacity transport mechanisms to be well absorbed in the small and large intestines and is designed to then rapidly convert to gabapentin upon absorption into the body. Besides gabapentin, the metabolic breakdown products of XP13512 are molecules that have undergone extensive safety testing and are found naturally in mammals and in food. Phase 1 clinical trials in healthy volunteers have demonstrated that, in contrast to Neurontin, oral administration of XP13512 produces dose-proportional blood levels of gabapentin across a broad range of doses. Additional Phase 1 clinical trials with a sustained-release formulation of XP13512 have demonstrated that, compared to equivalent doses of Neurontin, XP13512 produced higher levels of gabapentin in the blood for a longer period of time. XP13512 was well tolerated in all Phase 1 clinical trials. In addition to RLS, XP13512 has been shown in a Phase 2a clinical trial to be effective for the management of post-herpetic neuralgia.
About Restless Legs Syndrome, or RLS
Restless legs syndrome is a common, under-diagnosed neurological disorder that frequently manifests itself as a sleep disorder. Patients who suffer from RLS experience an irresistible urge to move their legs. This urge is usually accompanied by unpleasant sensations of burning, creeping, tugging or tingling inside the patients' legs, ranging in severity from uncomfortable to painful. These RLS-related symptoms typically begin or worsen during periods of rest or inactivity, particularly when lying down or sitting, and may be temporarily relieved by movement such as walking or massaging the legs. Symptoms often worsen at night, and disturbed sleep is a common result of RLS. Left untreated, RLS may cause exhaustion, daytime fatigue, inability to concentrate and impaired memory. Although the exact prevalence rate of RLS is uncertain, a recent study has indicated that approximately 10% of patients visiting primary care physicians in five industrialized Western countries experience RLS symptoms at least weekly, with approximately 2% of patients visiting primary care physicians having symptoms severe enough to disrupt their quality of life.
About XP19986
XP19986 is designed to overcome the deficiencies of baclofen, a currently marketed 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.
About GERD and Baclofen
GERD is a digestive system disorder caused by inappropriate relaxations of the lower esophageal sphincter, which is a combination of muscles that controls the junction between the esophagus and the stomach. GERD is 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, including 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 successfully completed a Phase 2b clinical trial for the treatment of restless legs syndrome, or RLS, and a Phase 2a clinical trial for the management of post-herpetic neuralgia. XenoPort anticipates commencing Phase 3 clinical trials of XP13512 in RLS patients in the first half of 2006. XenoPort has also completed two Phase 1 clinical trials of XP19986, a Transported Prodrug of R-baclofen. These trials demonstrated that XP19986 was suitable for twice-a-day dosing and was well tolerated with few adverse events at the doses expected to be used in future clinical trials. XenoPort has commenced a Phase 2a clinical trial of XP19986 in gastroesophageal reflux disease, or GERD, patients.
To learn more about XenoPort, please visit the web site at http://www.xenoport.com/.
Forward-Looking Statements
This press release contains "forward-looking" statements, including, without limitation, all statements related to our future clinical development programs for XP13512 and XP19986 and the timing thereof; the therapeutic and commercial potential of XP13512 and XP19986; future preclinical and 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 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 September 30, 2005, filed with the Securities and Exchange Commission on November 3, 2005. 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 is a registered U.S. trademark.
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