The Search for an MS Pill Continues
The holy grail in multiple sclerosis—other than cure—is oral disease-modifying therapy. All of the currently available, immunomodulating drugs must be injected, either SQ or IM by the patient herself or IV in the doctor's office. So anyone who cares about MS is watching the clinical development of Biogen Idec's oral drug fumarate (or Fumaderm* or BG00012 or BG-12) with a fair amount of interest.
And to that end, placebo-controlled phase 2b data were just published in the latest issue of The Lancet. These data show that fumarate, 240 mg tid, significantly reduced the number of new MS brain lesions at 3-6 months, including new active lesions (ie, gadolinium enhancing) by nearly 70%, in patients with relapsing MS. What's not so impressive is that fumarate reduced the annualized relapse rate by only about 30%, when compared with placebo, a relative reduction that did not reach statistical significance.** (Although a press release indicates that the study was not adequately powered to evaluate relapse endpoints.)
Nevertheless, these clinical data support the ongoing phase 3 investigation of fumarate (here and here), which is believed to work by activating a transcription factor (NRF2) that has cellular antioxidant properties. One phase 3 trial is using glatiramer acetate (Copaxone; Teva) as a comparator drug; the other is placebo controlled. The primary endpoint of both trials is clinical relapses.
Other novel, oral agents in phase 3 development for relapsing MS include fingolimod (Novartis), laquinimod (Teva), and teriflunomide (sanofi-aventis). Laquinimod is being compared with interferon beta-1a IM (Avonex; Biogen Idec), and the fingolimod and terifunomide studies are placebo controlled.
If fumarate prevails in phase 3 studies and becomes FDA approved, Biogen Idec will have a nice trifecta (triumvirate?) of immunomodulatory agents for MS: oral Fumaderm, IM Avonex, and IV Tysabri (natalizumab).
* FumaDERM?
** But this placebo-controlled rate reduction is comparable to that with the interferon betas.
