Dexpramipexole in ALS: Cautious Optimism

The only pharmacological agent proven to slow disease progression in amyotrophic lateral sclerosis (ALS) is riluzole, and its efficacy is quite modest, prolonging survival on average by only 2 to 3 months. Given this somewhat bleak background, the recently reported results of a phase II trial of dexpramipexole, a putative mitochondrial modulator, are of particular interest to patients with ALS and the neurologists who provide their care. This multicenter trial proceeded in two parts. In part 1, 102 patients were randomized to receive placebo or dexpramipexole at 50 mg, 150 mg, or 300 mg per day for 12 weeks. In part 2, after 4 weeks of drug washout, 92 patients were available for re-randomization to receive dexpramipexole at 50 mg or 300 mg per day for 24 weeks.

Overall, the drug was safe and well tolerated; the only notable adverse effect was reversible neutropenia in five patients. A hint of clinical benefit with dexpramipexole in the slowing of disease progression was observed on some outcome measures — e.g., median decline in ALS Functional Rating Scale–Revised (ALSFRS-R) scores was slower with 300 mg of dexpramipexole compared with placebo; and treatment failures, defined as a ≥6-point drop in ALSFRS-R score in part 1, were less frequent with 150 mg and 300 mg of dexpramipexole than with placebo. But no clinical benefit was found on other measures — e.g., slope of ALSFRS-R scores and slope of upright vital capacity.