Surprise for Sarepta
On December 12, the US Food and Drug Administration (FDA) approved Sarepta’s Duchenne muscular dystrophy therapy Vyondys 53. The agency had rejected the same drug four months ago because of safety concerns.
The industry was surprised, according to an article by Ned Pagliarulo and Jonathan Gardner in BioPharma Dive. Sarepta had not said anything to the public about resubmitting an application to the FDA, and reversing a rejection so quickly is very unusual for the agency.
After the FDA’s rejection in August, Sarepta appealed the decision through a formal dispute resolution process. Peter Stein, the director of the FDA’s Office of New Drugs, resolved the issues noted in the Complete Response Letter sent to Sarepta, according to the company, and allowed the appeal. Then Sarepta filed its application again and received approval.
Sarepta Therapeutics, Inc., a medical research and drug development company with corporate offices and research facilities in Cambridge, Massachusetts, was incorporated in 1980 as AntiVirals. Before going public, the company changed its name to AVI BioPharma. In July 2012 the name was changed to Sarepta Therapeutics. As of 2018, the company has one approved drug.
The FDA has conditionally cleared Vyondys 53, a type of nucleic acid therapy, for the roughly 8 percent of patients with Duchenne who are “amenable” to exon 53 skipping, the mechanism by which the drug works. Sarepta plans to price Vyondys 53 “at parity” with Exondys 51, which controversially won FDA approval in 2016. Exondys 51 costs about $300,000 per year per child. Exondys 51, the first medicine specifically approved to treat Duchenne, covered about 13 percent of patients. After it was approved, there was internal debate at the FDA.
When the FDA rejected Vyondys 53, people thought it was for political reasons related to the controversy over Exondys 51. Sarepta CEO Doug Ingram refused to talk much about the decision other than that it related to infection and kidney toxicity risks.
Approval is contingent upon Sarepta running a confirmatory study to prove Vyondys 53 provides a clinical benefit. Data in the application showed that treatment boosted levels of dystrophin, a critical muscle protein missing in patients with DMD, from 0.1 percent of normal to 1.02 percent on average after 48 weeks.
Sarepta’s primary products are Morpholino oligomers (PMOs), synthetic nucleic acid analogs conceived of by James Summerton and invented by Summerton with Dwight Weller, originally developed under the name NeuGene Antisense. Because morpholino oligomers can form sequence-specific double-stranded complexes with RNA, they are suitable for use in antisense therapy.
The Morpholino drug eteplirsen, targeting exon 51 of the dystrophin mRNA, was approved as a human therapeutic by the FDA in 2016. Clinical trials for Morpholinos targeting other exons are ongoing. Morpholinos have been used in preclinical studies to inhibit replication of a broad range of viruses, including influenza, West Nile virus, SARS, hepatitis C, dengue fever, Ebola and Calicivirus, all of which are single-stranded RNA viruses. AVI has conducted six human trials for colorectal and pancreatic cancers using the cancer vaccine AVICINE.
