XenoPort Announces XP21279 Phase 2 Clinical Trial Results in Patients With Advanced Parkinson's Disease
SANTA CLARA, Calif.--(BUSINESS WIRE)--Dec 5, 2011 - XenoPort, Inc. (Nasdaq:XNPT) announced today preliminary top-line results of a Phase 2, randomized, crossover clinical trial that compared optimized treatment with either Sinemet (immediate-release levodopa/carbidopa) or XP21279 co-formulated with carbidopa (279/CD) in advanced Parkinson's disease patients with motor fluctuations. 279/CD dosed three times per day reduced mean daily “off time” by 46% compared to baseline when the patients were taking their pre-trial Sinemet dosing regimen. However, in the primary analysis of the trial, the improvement with 279/CD was not statistically better than the improvement seen with optimized Sinemet dosed four or five times per day during the double-blind phase of the trial.
The trial enrolled subjects at 12 U.S. sites who were on a stable regimen of Sinemet dosed four or five times per day. Subjects were required to have “off time” in at least half of the inter-dose intervals between the first and last daily doses of Sinemet and an average daily “off time” greater than or equal to two hours during the three day baseline assessment period.
The trial consisted of an open-label, crossover optimization phase followed by a double-blind, crossover treatment phase. Thirty-five subjects entered the open-label phase of the trial, during which doses of Sinemet and 279/CD were each optimized for two weeks in a random order using the same protocol-specified guidelines. For Sinemet, doses were optimized while maintaining the same four or five times per day dosing frequency that the subject was taking during the baseline period. For 279/CD, doses were optimized using a fixed three times per day regimen. Qualified subjects then entered the double-blind phase, during which they received the optimized doses of Sinemet and 279/CD for two weeks each in random order.
The primary analysis was performed on the difference between Sinemet and 279/CD in the change from baseline in mean daily “off time” at the end of each period during the double-blind phase of the trial. The efficacy analysis included 28 subjects who completed the double-blind phase of the trial. The baseline mean daily “off time” for the analysis population was 6.4 hours. At the end of the open-label phase, mean daily “off time” was reduced from baseline by 2.0 hours for Sinemet compared to 3.4 hours for 279/CD. At the end of the double-blind phase, mean daily “off time” was reduced from baseline by 2.6 hours for Sinemet compared to 2.9 hours for 279/CD. The mean difference between Sinemet and 279/CD at the end of the double-blind phase of the trial was not statistically significant.
Robustness analysis included in the pre-specified statistical plan identified four subjects with outlier “off-time” values based on predefined criteria and evaluated the impact of these subjects on the trial results. Excluding these subjects, the baseline mean daily “off time” was 6.1 hours. At the end of the open-label phase, mean daily “off time” was reduced from baseline by 1.9 hours for Sinemet compared to 3.5 hours for 279/CD. At the end of the double-blind phase, mean daily “off time” was reduced from baseline by 2.4 hours for Sinemet compared to 3.3 hours for 279/CD. Excluding these outliers, the mean difference between Sinemet and 279/CD at the end of the double-blind phase of the trial was statistically significant (p<0.05).
All treatment-emergent adverse events were mild to moderate in severity. During the double-blind phase of the trial, dyskinesias were the most common adverse event. The incidence of new or worsening dyskinesias during the double-blind phase of the trial was 11% for Sinemet and 13% for 279/CD. There were no serious adverse events.
The trial employed a bi-layer tablet formulation containing both XP21279 and carbidopa. Pharmacokinetic analyses were performed on a subset of subjects during the open-label phase of the trial. The preliminary results indicate that the bi-layer tablet formulation provided a sustained levodopa exposure that was consistent with XenoPort's prior open-label trial that utilized separate extended-release XP21279 and commercially-available carbidopa tablets.
Ronald W. Barrett, Ph.D., chief executive officer of XenoPort, stated, “While we observed an impressive reduction from baseline in ˜off time' for 279/CD dosed three times per day, we are disappointed that this trial did not provide a clear indication of the benefit, other than dosing frequency, of 279/CD for advanced Parkinson's disease patients compared to optimized doses of Sinemet. This may have been due to the large reduction from baseline in ˜off time' observed once patients had their Sinemet dose optimized within the trial. Given that the goal of the trial was to demonstrate a clinical benefit over Sinemet, it was important that both treatments were equivalently optimized using specific guidelines. We intend to further analyze these data, including investigation of possible explanations for the outliers. We also plan to discuss these results with Parkinson's disease experts and possibly with regulatory authorities to determine next steps, if any. We will defer further investment in this program pending the outcome of our data analysis and these discussions.”
XP21279 is a patented new chemical entity that is a Transported Prodrug of levodopa. XP21279 is designed to utilize natural nutrient transport mechanisms located throughout the length of the gastrointestinal (GI) tract, enabling rapid absorption and conversion to levodopa by the body's naturally-occurring enzymes. XP21279 is designed to be well absorbed from the lower GI tract and is formulated for sustained release, which has been shown to reduce fluctuations of levodopa levels in the bloodstream compared to Sinemet.
About Parkinson's Disease
Parkinson's disease is a motor system disorder that results from the loss of dopamine-producing nerve cells in the brain. Dopamine is a chemical that is naturally produced by the body. It is responsible for smooth, coordinated function of the body's muscles and movement. When approximately 80% of dopamine-producing cells are damaged, the symptoms of Parkinson's disease appear. The primary symptoms of Parkinson's disease are tremor or shaking, slowness of movement, rigidity or stiffness and difficulty with balance. It is estimated that 1.5 million people in North America are living with Parkinson's disease.
XenoPort is a biopharmaceutical company focused on developing and commercializing a portfolio of internally discovered product candidates for the potential treatment of neurological disorders. Horizant™ (gabapentin enacarbil) Extended-Release Tablets is XenoPort's first FDA-approved product. GlaxoSmithKline holds commercialization rights and certain development rights for gabapentin enacarbil in the United States. Gabapentin enacarbil is being developed in partnership with Astellas Pharma Inc. for the potential treatment of restless legs syndrome in Japan and several other Asian countries. XenoPort holds all other world-wide rights and has co-promotion and certain development rights to gabapentin enacarbil in the United States. XenoPort's pipeline of product candidates includes potential treatments for patients with neuropathic pain, spasticity 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 XenoPort's future clinical development and regulatory plans for XP21279; the therapeutic and commercial potential of XP21279; and the suitability of XP21279 as a treatment for patients with Parkinson's disease. 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 “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will” 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 risk that any future development of XP21279 for Parkinson's disease may not demonstrate safety and efficacy and risks related to the uncertain therapeutic and commercial value of XP21279 and XenoPort's need for additional funding. 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 September 30, 2011, filed with the Securities and Exchange Commission on November 4, 2011. 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.
Horizant is a trademark of GlaxoSmithKline.
Contact: XenoPort, Inc.
Jackie Cossmon, 408-616-7220
Posted: December 2011