Target Health Blog

FDA Approves First Drug For Spinal Muscular Atrophy

January 9, 2017


Spinal muscular atrophy (SMA), is a hereditary disease that causes weakness and muscle wasting because of the loss of lower motor neurons controlling movement. There is wide variability in age of onset, symptoms and rate of progression.

SMA types 1 through 4 all result from a single known cause – a deficiency of a protein called SMN, for survival of motor neuron. Deficiency of SMN protein occurs when a mutation is present in both copies of the SMN1 gene one on each chromosome 5. When SMA symptoms are present at birth or by the age of 6 months, the disease is called type 1 SMA (also called infantile onset or Werdnig-Hoffmann disease). Babies typically have generalized muscle weakness, a weak cry and breathing distress. They often have difficulty swallowing and sucking, and don’t reach the developmental milestone of being able to sit up unassisted. Typically these babies have two copies of the SMN2 gene, one on each chromosome 5. Over half of all new SMA cases are SMA type 1. When SMA has its onset between the ages of 7 and 18 months and before the child can stand or walk independently, it is called type 2 or intermediate SMA. Children with type 2 SMA generally have at least three SMN2 genes. Late-onset SMA (also known as types 3 and 4 SMA, mild SMA, adult-onset SMA and Kugelberg-Welander disease) results in variable levels of weakness. Type 3 SMA has its onset after 18 months, and children can stand and walk independently, although they may require assistance. Type 4 SMA has its onset in adulthood, and people are able to walk during their adult years. People with types 3 or 4 SMA generally have between four and eight SMN2 genes, from which a fair amount of full-length SMN protein can be produced.

The FDA has approved Spinraza (nusinersen) for use across the range of SMA patients. Spinraza is the first drug approved to treat children and adults with SMA, is administered by injection into the fluid surrounding the spinal cord. The efficacy of Spinraza was demonstrated in a clinical trial in 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. Patients were randomized to receive an injection of Spinraza, into the fluid surrounding the spinal cord, or undergo a mock procedure without drug injection (a skin prick). Twice the number of patients received Spinraza compared to those who underwent the mock procedure. The trial assessed the percentage of patients with improvement in motor milestones, such as head control, sitting, ability to kick in supine position, rolling, crawling, standing and walking.

The FDA worked closely with the sponsor during development to help design and implement the analysis upon which this approval was based. The FDA asked the sponsor to conduct an interim analysis as a way to evaluate the study results as early as possible. A total of 82 of the 121 treated patients were eligible for this analysis. Results showed that 40% of patients treated with Spinraza 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 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 most common side effects found in participants in the clinical trials on Spinraza were upper respiratory infection, lower respiratory infection and constipation. Warnings and precautions include low blood platelet count and toxicity to the kidneys (renal toxicity). Toxicity in the nervous system (neurotoxicity) was observed in animal studies.

The FDA granted this application fast track designation and priority review. The drug also received orphan drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The sponsor is also receiving a rare pediatric disease priority review voucher under a program intended to encourage development of new drugs and biologics for the prevention and treatment of rare pediatric diseases. A voucher can be redeemed by a sponsor at a later date to receive priority review of a subsequent marketing application for a different product. This is the eighth rare pediatric disease priority review voucher issued by the FDA since the program began.

Spinraza is marketed by Biogen of Cambridge, Massachusetts and was developed by Ionis Pharmaceuticals of Carlsbad, California.

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