Sarepta Therapeutics has won FDA approval of Exondys 51 (eteplirsen), the first drug sanctioned for treating Duchenne muscular dystrophy. Afflicting one in every 3,500 to 5,000 boys, DMD is a fatal genetic disorder characterized by progressive muscle deterioration.
Approved under an accelerated program for drugs that treat life-threatening diseases, Exondys 51 is being made available on the basis of initial clinical data. “We eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial that the company must conduct,” says Janet Woodcock, director of FDA’s Center for Drug Evaluation & Research.
DMD is caused by mutations in the gene encoding for dystrophin, a protein that keeps muscle cells intact. Sarepta’s phosphorodiamidate morpholino oligomers prevent the reading of faulty gene regions during mRNA processing. This “exon skipping” method enables production of a truncated, but still functional, protein.
Up to 80% of DMD patients have genotypes open to exon skipping, and about 13% involve the exon 51 targeted by Exondys 51. Approval was granted because of an observed increase in dystrophin in some patients. Further studies will determine whether the drug improves motor function. If they fail to verify any clinical benefit, the FDA may move to pull its approval.
Indeed, the drug’s lack of proven efficacy caused FDA advisers to recommend against approving it. Other companies also have had trouble getting FDA to accept approval applications, including BioMarin, which has a drug targeting exon 51, and PTC Therapeutics, which sells the DMD drug ataluren in Europe.
Sarepta plans an immediate U.S. launch of Exondys 51 at a price tag of $300,000 per year. And with its stock price recently doubling, the company announced a $225 million stock offering. It intends to use the money to support clinical studies, manufacturing, and commercialization.
Debra Miller, founder and CEO of CureDuchenne, a nonprofit group that helped move Exondys 51 into clinical studies, lauded the approval but calls it “only a starting point for more research and discovery.” Sarepta has two other exon-skipping drugs in clinical trials and five more in preclinical development.
CORRECTION: This story was updated on Sept. 30, 2016, to correct a structure error in the illustration.