In January the experimental drug dexpramipexole to treat amyotrophic lateral sclerosis (ALS) joined the junk heap of over 20 failed experimental drugs to treat the debilitating condition, also known as motor neuron disease. Biogen Idec of Weston, Massachusetts, discontinued clinical studies after a phase 3 trial of 943 patients showed no benefit. “We looked at function, survival, respiratory decline and even performed subgroup analyses,” explains Douglas Kerr, director of neurodegeneration clinical research at Biogen Idec. “Quite simply the drug did not work, not on any measure.” The results were a blow to the ALS research community, adds Steve Perrin, CEO of the nonprofit ALS Therapy Development Institute in Cambridge, Massachusetts, as phase 2 results had suggested a 39% slowing in disease progression rate compared to placebo. What has emerged from this and other failed ALS drug candidates is that the phase 2 studies were too underpowered to reliably gauge phase 3 outcomes, Perrin says. “We are trying to do too many things in the phase 2 trials. Either pick your dose so there are more patients in your group or power your studies a lot higher.” Compounding the difficulties is the heterogeneity of ALS and the lack of biomarkers to track disease progression. Next in line are Cytokinetics' Tirasemtiv, BrainStorm Cell Therapeutics' NurOwn, Neuraltus Phamaceuticals' NP001, GlaxoSmithKline's Ozanezumab and Novartis' Gilenya, all currently in phase 2. “The failures show that these drugs should move through early trials cautiously,” says Perrin. In February, the US Food and Drug Administration held a public hearing to garner input from the ALS community. Comments are due by March 25.