FDA Approves First Drug for Spinal Muscular Atrophy

New therapy addresses unmet need for rare disease

The FDA has given the nod to nusinersen (Spinraza, Biogen/Ionis Pharmaceuticals), the first drug approved to treat children and adults with spinal muscular atrophy (SMA), a rare and often fatal genetic disease affecting muscle strength and movement. Nusinersen is an injection administered into the fluid surrounding the spinal cord.

“There has been a long-standing need for a treatment for spinal muscular atrophy, the most common genetic cause of death in infants, and a disease that can affect people at any stage of life,” said Billy Dunn, MD, director of the Division of Neurology Products at the FDA’s Center for Drug Evaluation and Research.

SMA is a hereditary disease that causes weakness and muscle wasting because of the loss of lower motor neurons controlling movement. Age at onset, symptoms, and rate of progression vary widely. Nusinersen is approved for use across the range of SMA patients.

The efficacy of nusinersen was demonstrated in a study of 121 patients with infantile-onset SMA who were diagnosed before 6 months of age and who were less than 7 months old at the time of their first dose. The patients were randomly assigned to receive an injection of nusinersen into the fluid surrounding the spinal cord or to undergo a mock procedure without drug injection (a skin prick). Twice the number of patients received nusinersen compared with those who underwent the mock procedure. The study assessed the percentage of patients with improvement in motor milestones, such as head control, sitting, the ability to kick in a supine position, rolling, crawling, standing, and walking.

The FDA asked the sponsor to conduct an interim analysis as a way to evaluate the study results as early as possible; 82 of the 121 patients were eligible for this analysis. Forty percent of the patients treated with nusinersen achieved an improvement in motor milestones as defined in the study, whereas none of the control patients did.

Additional open-label, uncontrolled studies were conducted in symptomatic patients ranging in age from 30 days to 15 years at the time of the first dose, and in presymptomatic patients ranging in age from eight days to 42 days at the time of the first dose. These studies lacked control groups, but the findings appeared to support the clinical efficacy of nusinersen in the controlled trial in infantile-onset patients.

The most common adverse effects associated with nusinersen in clinical studies included upper and lower respiratory tract infections and constipation. Warnings and precautions include low platelet counts and renal toxicity. Neurotoxicity was observed in animal studies.

Source: FDA; December 23, 2016.