In early January 2013, Biogen Idec announced that, unfortunately, its phase 3 "EMPOWER" trial of dexpramipexole showed that the drug had no apparent effect on function or survival in amyotrophic lateral sclerosis (ALS), and the company had discontinued development of the drug for ALS.
In a 15-minute podcast, MDA Executive Vice President of Research and Medical Director Valerie Cwik talked with Douglas Kerr, director of Neurodegeneration Clinical Research at Biogen Idec, about the details of the trial results and Biogen Idec's continued commitment to ALS research.
Dexpramipexole demonstrated neuroprotective properties in early-stage studies involving cell cultures and animal models, and was thought to work by improving the function and efficiency of cellular "energy factories" called mitochondria. Scientists know that in ALS, mitochondrial dysfunction can contribute to the death of motor neurons.
The phase 2 trial of the drug— which was significantly smaller in size than the phase 3 trial — showed the drug was safe and suggested it might have some beneficial effects.
The phase 3 trial enrolled 943 people with ALS at 81 sites in 11 countries, with participants randomly assigned to receive either dexpramipexole or a placebo.
In analyzing trial data, investigators made every effort to determine whether dexpramipexole offered “any hint of efficacy,” including examining multiple endpoints such as muscle function, survival and pulmonary function. In addition, they verified that participants took the medication as directed and looked for effects in subgroups of participants (based on parameters such as gender, age, rate of progression and trial site).
Despite the occurrence of some adverse events in earlier trials (for example, the temporary reduction in the number of white blood cells — called neutropenia — in some participants) dexpramipexole was found to be safe and well-tolerated. The safety profile for the drug did not change in the phase 3 trial, Kerr said.
Because the EMPOWER trial was one of the largest and most comprehensive ALS studies that has ever been done, a great deal of clinical data gathered during the trial will help researchers better understand ALS and improve the design of future clinical trials.
Biogen Idec is "tremendously disappointed" by the results, Kerr said. The company expressed gratitude to patients, caregivers and everyone in the ALS community for their dedication in testing dexpramipexole and reaffirmed its commitment to the ALS community.
A planned open-label extension study called ENVISION also was terminated due to the phase 3 results.
Despite the disappointing results, Kerr said Biogen Idec remains "undaunted," and "passionately committed" to drug development in ALS. The company has a global infrastructure in place for ALS trials and several therapies in the early stages of development. (Note: Biogen Idec recently formed a first-of-its-kind ALS research consortium to identify ALS drug targets in collaboration with several leading academic research centers, and entered into a collaboration with Isis Pharmaceuticals to discover and develop "antisense" drugs to treat neurological disorders.)