Dexpramipexole Safe but Not Effective for ALS

Michael Benatar, MD, MS, PhD

The highly anticipated results of a large, multicenter, phase III, randomized, controlled trial of dexpramipexole show no benefit for patients with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive, ultimately fatal neurodegenerative disease for which effective treatments are almost entirely lacking. Based on a mechanism of action of enhancing mitochondrial function (a biological mechanism that has been implicated in ALS), evidence of a neuroprotective effect in in vitro assays, improved survival and retention of motor function in in vivo models of ALS, and promising phase II human data, researchers undertook a manufacturer-sponsored, premarket clinical trial of dexpramipexole in patients with ALS. EMPOWER was a randomized, double-blind, placebo-controlled, phase III trial conducted across 81 academic medical centers in 11 countries. The trial enrolled 943 participants, randomized 1:1 to receive either 150 mg dexpramipexole or placebo twice daily for 12 to 18 months.

Although dexpramipexole was generally well tolerated, there was no evidence of efficacy on the primary outcome measure (a combined assessment of function and survival) or on any of the predefined secondary outcome measures: time to death or respiratory insufficiency (tracheostomy or noninvasive ventilation for >22 hours/day), respiratory decline (time to reach 50% predicted upright slow vital capacity or death), change in muscle strength (measured using handheld dynamometry), or quality of life (measured using the ALS assessment questionnaire, ALSAQ-5). Available pharmacokinetic data confirmed the presence of dexpramipexole in concentrations similar to those reported in a prior phase II study.

Citation(s):

Cudkowicz ME et al. Dexpramipexole versus placebo for patients with amyotrophic lateral sclerosis (EMPOWER): A randomised, double-blind, phase 3 trial. Lancet Neurol 2013 Nov; 12:1059.