FDA OKs Nusinersen, First Drug for Spinal Muscular Atrophy

Megan Brooks

December 23, 2016

The US Food and Drug Administration (FDA) has approved nusinersen (Spinraza, Biogen and Ionis Pharmaceuticals), the first drug approved to treat children and adults with spinal muscular atrophy (SMA), a rare and often fatal genetic disease.

SMA, which affects around 1 in every 11,000 births, is a progressive motor neuron disorder causing muscle weakness and difficulties breathing and eating. There is wide variability in age of onset, symptoms, and rate of progression. Nusinersen is approved for use across the range of patients with SMA, the FDA said.

Nusinersen, which is administered via injection into cerebrospinal fluid, is an antisense oligonucleotide aimed at increasing concentrations of survival motor neuron (SMN) protein, which is underexpressed in SMA.

The efficacy of nusinersen was shown in a clinical trial in 121 patients with infantile-onset SMA who were diagnosed before 6 months of age and who were younger than 7 months at the time of their first dose. Patients were randomly allocated to receive an injection of nusinersen or a mock procedure without drug injection (control group).

An interim analysis performed at the request of the FDA showed that 40% of patients treated with nusinersen achieved improvement in motor milestones, as defined in the study, whereas none of the control patients did.

Additional open-label uncontrolled clinical studies were conducted in symptomatic patients who ranged in age from 30 days to 15 years at the time of the first dose, and in presymptomatic patients who ranged in age from 8 days to 42 days at the time of the first dose.

"These studies lacked control groups and therefore were more difficult to interpret than the controlled study, but the findings appeared generally supportive of the clinical efficacy demonstrated in the controlled clinical trial in infantile-onset patients," the FDA said in a news release.

"There has been a long-standing need for a treatment for [SMA], the most common genetic cause of death in infants, and a disease that can affect people at any stage of life," Billy Dunn, MD, director of the Division of Neurology Products in the FDA's Center for Drug Evaluation and Research, said in the release.

"As shown by our suggestion to the sponsor to analyze the results of the study earlier than planned, the FDA is committed to assisting with the development and approval of safe and effective drugs for rare diseases and we worked hard to review this application quickly; we could not be more pleased to have the first approved treatment for this debilitating disease," Dr Dunn said.

"With the approval today of SPINRAZA, the future for those affected with SMA has changed. We are especially pleased that this sophisticated and rigorous clinical development plan has resulted in a broad label that may offer access to many patients," said Kenneth Hobby, president at Cure SMA, in a company news release. "This has been a story of all groups — families, researchers, companies and the FDA — working together as one community."

The most common adverse effects seen with nusinersen were upper respiratory infection, lower respiratory infection, and constipation. Warnings and precautions include low blood platelet count and renal toxicity. Neurotoxicity was observed in animal studies.

Nusinersen had fast-track designation and received priority review by the FDA. The drug also had orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

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