Assistant

XenoPort Inc.'s gabapentin prodrug XP13512 edged closer to the market after yielding positive results in a second Phase III trial in restless legs syndrome (RLS).

Results from a third and final Phase III study are expected later this quarter and, assuming another positive outcome, partner GlaxoSmithKline plc is expected to file a new drug application in the third quarter.

If approved, XP13512 would be the first gabapentin drug available for RLS, a chronic condition characterized by burning, creeping, tugging or tingling sensations in the legs that forces patients to move to alleviate discomfort, and, as a result, often disrupts sleep.

Existing drugs, which include GSK's Requip and Mirapexin from German pharma Boehringer Ingelheim GmbH, are dopamine agonists and, while they have proved efficacious against RLS, XenoPort believes XP13512 treats the "compendium of symptoms," Ronald Barrett, CEO of Santa Clara, Calif.-based XenoPort said during a conference call.

It also offers a "different side effect profile" from dopamine agonists, which can cause augmentation and compulsive behavior with chronic use, he added.

The 36-week study was composed of 24 weeks in which all 327 patients received 1,200 mg of XP13512, followed by a 12-week placebo-controlled portion involving only responders to determine the drug's ability to reduce the rate of relapse. Of the 221 patients to complete the first portion of the trial, 198, or 88 percent, were considered responders.

Data showed that treatment with the drug resulted in a statistically significant lower proportion of relapse compared to placebo (9 percent vs. 23 percent).

"We were particularly pleased with these results in the face of the stringent relapse criteria that were arrived at after extensive discussions with the FDA," Barrett noted.

The trial was designed specifically to determine relapse rate, which was defined by a patient's withdrawal from the trial due to lack of efficacy and/or working scores on the International RLS scale or the Investigator Clinical Global Impression of Improvement scale.

Similarly designed studies with dopamine agonists also have yielded positive relapse results - for instance, Phase III data included in the NDA for Requip showed that patients who followed up 24 weeks on the drug with an additional 12 weeks of treatment had a lower relapse rate than patients who were switched to placebo for the final 12 weeks (32.6 percent vs. 57.8 percent) - but Barrett urged "caution against comparison," and highlighted XP13512's safety data.

During the 24-week single-blind portion of the study, 7 percent of XP13512-treated patients withdrew due to adverse events, the most common of which were somnolence (30 percent) and dizziness (22 percent), which were usually mild to moderate and transient in nature. In the placebo-controlled part, 0 percent of XP13512-treated patients withdrew due to adverse effects compared to 3 percent in the placebo group.

One death occurred in the study, but it was determined to be unrelated to treatment and of five other serious adverse events, only one possibly was linked to XP13512.

Despite the news, XenoPort's stock (NASDAQ:XNPT) slid 2.2 percent, or $1.34, Tuesday to close at $59.78, but that result probably isn't a reaction to those data.

Analyst David Amsellem, of Friedman, Billings, Ramsey, downgraded the firm's stock last month, stating further trial data already are priced into its shares, which soared 44 percent to $41.56 in April on positive results from the first Phase III study and have continued to climb ever since. (See BioWorld Today, April 26, 2007.)

XenoPort also is completing a one-year safety study of XP13512, and Barrett told investors that more than 100 patients already have finished 12 months of treatment. That data also will be forwarded to GSK for inclusion in the upcoming NDA.

London-based GSK has the responsibility of regulatory filing under the companies' February 2007 deal, which gives GSK worldwide rights, except for certain Asian territories, to XP13512 in RLS and neuropathic pain indications in exchange for up to $640 million in up-front and milestone payments. (See BioWorld Today, Feb. 9, 2007.)

The product is partnered with Tokyo-based Astellas Pharma Inc. for development and commercialization in Japan, Korea, the Philippines, Indonesia, Thailand and Taiwan.

Elsewhere in its pipeline, XenoPort has XP19986, which recently began testing in Phase II trials in gastroesophageal reflux disease and in spinal cord injury patients with spasticity, and XP21279, which entered the clinic earlier this month in Parkinson's disease.

The company also has XP21510, a preclinical candidate that it partnered last year with Newport, Ky.-based Xanodyne Pharmaceuticals Inc. in a potential $147 million deal. XP21510, a transported prodrug of tranexamic acid, is in development for menorrhagia.