XenoPort, Inc. (Nasdaq:XNPT) announced today the preliminary results from two Phase 1 studies with XP23829, a novel fumaric acid ester compound that is a prodrug of monomethyl fumarate (MMF). Based on the favorable preliminary results from these studies, XenoPort intends to continue to advance the development of XP23829 as a potential treatment for patients with relapsing-remitting multiple sclerosis (RRMS) and/or psoriasis.
Ronald W. Barrett, Ph.D., chief executive officer of XenoPort, Inc., stated, “The results of these recent studies affirm our belief in the potential of XP23829 to be a next generation fumaric acid ester-based medicine. We now intend to finalize dose and formulation selection as well as other aspects of our development plans over the next few months.”
The first Phase 1 study was a randomized, double-blind, placebo-controlled, multiple ascending dose-escalation study of the pharmacokinetics, safety and tolerability of two formulations of XP23829 in healthy adult subjects. Five separate cohorts (12 active and three placebo subjects per cohort) were enrolled sequentially and received one of two formulations of XP23829 dosed with or without food. Following up-titration of up to five days, dosing for each cohort ranged from 400 to 1,000 mg XP23829 per day, administered either once a day (QD) or twice a day (BID), with dosing for an additional six days. On the seventh day of target dose administration, pharmacokinetic (PK) evaluations were conducted following the morning dose. Similarly, a sixth cohort of healthy subjects received 240 mg BID TECFIDERA
(dimethyl fumarate), which is also a prodrug of MMF. As a consequence of its higher molecular weight, 400 mg of XP23829 is approximately equimolar to 240 mg of dimethyl fumarate (DMF), i.e., these amounts of each compound can potentially be enzymatically converted to approximately the same amount of MMF.
The preliminary results of the first Phase 1 study showed that both formulations of XP23829 produced MMF in the plasma but with different PK profiles. The 400 mg BID XP23829 Formulation 1 dosed without food provided an MMF PK profile that was nearly identical to that of 240 mg BID TECFIDERA dosed without food. As expected, XP23829 Formulation 2, administered as 800 mg QD and 500 mg BID dosed with food, provided more extended exposure to MMF. These cohorts had a lower mean maximal plasma concentration (Cmax) of MMF, while providing a mean daily area under the concentration versus time curve (AUC) of MMF that was approximately 25% less than that seen after dosing 240 mg BID TECFIDERA. XP23829 was generally well tolerated in the study. The most common adverse events were flushing and gastrointestinal-related events, which were generally mild to moderate in severity.