12:00 AM
Oct 15, 2012
 |  BioCentury  |  Product Development

Bettering BG-12

XenoPort aims for better version of Biogen Idec's BG-12 for MS, maybe psoriasis

Physicians who treat multiple sclerosis have been looking forward to getting access to Biogen Idec Inc.'s BG-12 based on its efficacy, safety and oral dosing. Now XenoPort Inc. is seeking to build a better version with XP23829, an asymmetrical diester prodrug of monomethyl fumarate.

The compound cleared its first clinical hurdle early this month when XenoPort reported Phase I safety and pharmacokinetic data that suggest potential for once-daily dosing and fewer side effects than BG-12.

BG-12 is an oral formulation of dimethyl fumarate (DMF). DMF acts like a prodrug in that it is rapidly converted to monomethyl fumarate (MMF) after absorption in the gut. MMF then activates the nuclear factor (erythroid-derived 2)-like 2 (NFE2L2; NRF2) pathway, which triggers antioxidant and anti-inflammatory effects.

A twice-daily regimen of BG-12 is under regulatory review in the U.S. and the EU to treat relapsing-remitting MS (RRMS). FDA's decision is expected by year end.

In the Phase III DEFINE and CONFIRM trials, BG-12 showed efficacy comparable to or better than standard-of-care injectables with better safety or efficacy than oral alternatives. However, it is associated with flushing and nausea, diarrhea and abdominal pain (see BioCentury, Aug. 15, 2011).

In DEFINE, gastrointestinal adverse events were the cause of 5-6% of discontinuations in patients receiving BG-12 vs. 1% of discontinuations in patients receiving placebo.

Flushing was the most common adverse event in DEFINE and CONFIRM, reported in 24-38% of patients. In DEFINE flushing was the cause of 1-2% of discontinuations vs. <1% in placebo.

"This can be a nuisance to some patients and does...

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