XenoPort Reports Favorable Metabolism and Pharmacokinetics of XP23829, a Novel Fumaric Acid Ester, in Phase 1 Trial
Intends to Advance Development for Potential RRMS and/or Psoriasis Treatment
SANTA CLARA, Calif.--(BUSINESS WIRE)-- XenoPort, Inc. (NAS: XNPT) announced today favorable preliminary results from a Phase 1 clinical trial in healthy adults designed to assess the pharmacokinetics (PK), safety and tolerability of single doses of four different oral formulations of XP23829, a novel fumaric acid ester compound that is a prodrug of monomethyl fumarate (MMF). XP23829 is being developed for the potential treatment of relapsing-remitting multiple sclerosis (RRMS) and/or psoriasis. The trial demonstrated that administration of XP23829 resulted in the expected levels of MMF in the blood. As anticipated, the four formulations produced different PK profiles of MMF, including one formulation that could potentially be dosed two or three times a day and at least one formulation that may be suitable for once-a-day dosing. XP23829 was generally well-tolerated in the trial.
Ronald W. Barrett, Ph.D., chief executive officer of XenoPort, said, "Given the broad potential therapeutic utility of XP23829, we are delighted that the results of this first Phase 1 trial achieved our goals by confirming the expected human metabolism of XP23829 and identifying formulations that we believe could be capable of achieving MMF exposures that are similar to MMF exposures observed in other fumaric acid ester therapies that have demonstrated effectiveness in psoriasis and RRMS. We are particularly pleased that the results suggest that the PK profile of at least one of our formulations supports further evaluation as a once-a-day treatment. We anticipate initiating further studies early next year, including a Phase 1, dose-escalation, multiple-dose study in healthy subjects, with the ultimate goal of developing a potential best-in-class fumaric acid ester-based medicine."
In the Phase 1 trial, 60 subjects were assigned to five cohorts of 12, and each cohort received one of four different formulations of XP23829 or placebo. Subjects received a single dose of XP23829 or placebo in both a fasted and fed state in a randomized order with a two-week period between dosing. All formulations of XP23829 were administered at a dose that was equivalent to 107 mg of MMF. Formulation 1 was a delayed-release formulation that was designed to suppress the release of XP23829 while in the stomach and then immediately release the drug upon entering the small intestine. Formulations 2, 3 and 4 were designed to delay and then slowly release XP23829.
All formulations of XP23829 produced MMF in the blood, while levels of intact XP23829 and the potential desmethyl-metabolite of XP23829 were below the limits of quantitation. The clearance of the promoiety, a pharmacologically inactive molecule that is also created in the enzymatic conversion of XP23829 to MMF, was rapid, with a half-life of about three hours.
As anticipated, when dosed in a fasted state, Formulation 1 produced a sharp peak in MMF blood levels and a PK profile that supports further evaluation for two- or three-times-a-day dosing. The maximum MMF concentrations after dosing Formulation 1 were lower and more variable when dosed with food.
Formulation 2 produced a total MMF exposure that was similar to that of Formulation 1, but with a lower maximum MMF concentration and a longer duration of exposure. The presence of food had minimal effect on the total exposure and PK profile of MMF. Given the duration of MMF exposure, the PK profile for Formulation 2 supports further evaluation as a once-a-day treatment. While Formulations 3 and 4 also produced sustained exposures of MMF, the total MMF exposures in blood were generally lower than Formulations 1 and 2.
XP23829 was generally well tolerated during the trial. All 12 subjects in each cohort completed both dosing periods. All adverse events were rated as mild. The only adverse events reported in more than one subject and more frequently for XP23829 than for placebo were flushing and "feeling hot." Of the 12 subjects in each cohort, the number of subjects reporting these adverse events was as follows:
XenoPort will host a conference call at 4:30 p.m. Eastern Time today to discuss its XP23829 clinical trial results and development program. To access the conference call via the Internet, go to www.XenoPort.com. To access the live conference call via phone, dial 1-888-275-3514. International callers may access the live call by dialing 706-679-1417. The reference number to enter the call is 38412003.
The replay of the conference call will be available for one week and may be accessed after 7:30 p.m. Eastern Time today via the Internet, at www.XenoPort.com, or via phone at 1-800-642-1687 for domestic callers, or 706-645-9291 for international callers. The reference number to enter the replay of the call is 38412003.
XP23829 is a fumaric acid ester compound that is a prodrug of MMF and for which U.S. Patent number 8,148,414 has been issued. Fumaric acid ester compounds have shown immuno-modulatory and neuroprotective effects in cell-based systems and preclinical models of disease. Dimethylfumarate (DMF), which is also a fumaric acid ester compound and a prodrug of MMF, has been shown to be effective in clinical trials in patients with RRMS and psoriasis. In XenoPort's preclinical animal studies that compared molar-equivalent doses of XP23829 to DMF, XP23829 demonstrated a greater degree of efficacy in both multiple sclerosis and psoriasis animal models. Toxicology studies conducted in two species showed that XP23829 caused less stomach irritation when compared to DMF.
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 approved in the United States for the treatment of moderate-to-severe primary restless legs syndrome (RLS) in adults and for the management of postherpetic neuralgia in adults. GlaxoSmithKline holds commercialization rights and certain development rights for Horizant in the United States. Regnite® (gabapentin enacarbil) Extended-Release Tablets is approved for the treatment of RLS in Japan. Astellas Pharma Inc. holds all development and commercialization rights for Regnite in Japan and five 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 spasticity, Parkinson's disease and RRMS.
To learn more about XenoPort, please visit the web site at http://www.XenoPort.com.
This press release contains "forward-looking" statements, including, without limitation, all statements related to the clinical development of XP23829 and the timing and results thereof; XenoPort's anticipated future clinical trials of XP23829, and the number and timing thereof; the potential suitability of XP23829 as a treatment for RRMS and/or psoriasis, including the potential suitability of XP23829 as a once-a-day treatment; and the therapeutic and commercial potential of XP23829 and XenoPort's other clinical product candidates. 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 "anticipate," "believe," "could," "goal," "intends," "may," "possible," "potential," "suggest," "would" 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, risks related to the uncertain results and timing of clinical trials and other studies, including the risk that success in preclinical testing and early clinical trials do not ensure that later clinical trials will be successful, and that the results of clinical trials by other parties may not be indicative of the results in trials that XenoPort may conduct; XenoPort's ability to successfully conduct clinical trials in the anticipated timeframes, or at all; XenoPort's dependence on its current and additional collaborative partners; the availability of resources to develop XenoPort's product candidates; and the uncertain therapeutic and commercial value of XenoPort's product candidates. 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 June 30, 2012, filed with the Securities and Exchange Commission on August 8, 2012. 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 Regnite are registered trademarks of XenoPort, Inc.
Horizant is a registered U.S. trademark of GlaxoSmithKline.
Jackie Cossmon, 408-616-7220
KEYWORDS: United States North America California
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