top of page

2017 Kicks Off with New Treatments for Pediatric Neuromuscular Disorders

Updated: Feb 18, 2021

The last week of December 2016 finds us with the first and second ever FDA-approved treatments for two groups of affected individuals with Duchenne (DMD) and spinal muscular atrophy (SMA). This long- awaited news arrives just in time to wrap up a year of milestone achievements which began August 30th with the Santhera Pharmaceuticals press release announcing the FDA grant to conduct a Phase 1 Study of Omigapil (CALLISTO) for the treatment of Congenital Muscular Dystrophy (CMD). These achievements were the product of a large team effort that starts with YOU, the affected individuals, families and caregivers, as the core of this team. You are surrounded by tenacious players: advocacy groups like Cure CMD, doctors, scientists, pharmaceutical and biotech companies, and the ever more incentivized federal regulatory’ norms and standards. The collective effort of all these players is key to facilitate development and expedite review of treatments intended to address our community’s unmet medical needs.

DMD & SMA: Same Drug Class Tailored for Two Different Diseases

DMD is caused by mutations in the dystrophin gene resulting in the absence of functional protein. This absence of functional dystrophin inevitably leads to muscle cell damage, progressive muscle deterioration, and weakness. As the disease progresses, life-threatening heart and respiratory conditions can occur. Yet just on September 19 of this year, the FDA announced its first-ever approved treatment for a pediatric muscular dystrophy. It is an injectable product called Exondys 51 (eteplirsen), sponsored by Sarepta Therapeutics. Approximately 13% of DMD patients may be amenable to treatment with this product, which is in the drug class “antisense oligonucleotide.” The treatment is a type of gene therapy called exon skipping, wherein the drug locates the mutation on the gene and causes cells to “skip” faulty or misaligned sections of genetic code leading to production of a shorter but functional version of the protein.

The second FDA-approved treatment for a pediatric neuromuscular condition was announced last week for SMA. This treatment is also an injectable product called SpinrazaTM (nusinersen), marketed by Biogen and developed by Ionis Pharmaceuticals. Typically, SMA is caused by mutations in the survival motor neuron gene 1 (SMN1), with additional variations in SMN2 and SMARD. People with typical SMA do not produce enough SMN protein, leading to weakness and muscle-wasting due to the loss of lower neurons that control movement. The severity of typical SMA correlates with the amount of SMN protein. All individuals affected by SMA have at least one copy of survival motor neuron gene 2 (SMN2), often referred to as the SMA "backup gene." Due to a splicing error, most of the SMN protein made by SMN2 is a low-efficiency replacement. Here again, the drug is an “antisense” that fixes the splicing error in the SMN2 gene, causing it to make more efficient SMN protein.

For the treatments above and Omigapil, the FDA granted “fast track designation,” “priority review,” “orphan drug designation,” and the manufacturers received a “rare pediatric disease priority review voucher,” which is a set of regulations and incentives created to assist and encourage the development of drugs for rare diseases.

How Might This Translate to CMD?

Antisense drugs can be tailored to target different sequences of a gene in order to bypass a genetic error and replace a missing or defective protein with a functional one. Several of the CMD subtypes may also be amenable to this kind of gene therapy. Other approaches might include inhibiting a defective gene and its protein product—in such cases, antisense drugs or a slightly different genetic intervention, such as Interference RNAs (iRNA, siRNA or shRNA) would be more suitable. Cure CMD is currently sponsoring projects designed to make these types of therapies a reality for the CMDs.

This excellent news about the two first FDA-approved treatments for pediatric DMD and SMA along with the earlier news about the FDA grant and fast track designation awarded for Omigapil in CMD fills us with confidence that we are moving forward in the right direction. Now, more than ever, we want to share the message with our entire CMD community that we need to stay focused, connected, engaged and committed to be successful in bringing treatments to reality for CMD. No doubt 2016 will be a landmark year for pediatric neuromuscular conditions—and may the New Year translate even more research into therapies! Happy 2017, Cheers!

bottom of page