Volume 94 Issue 38 | p. 13 | News of The Week
Issue Date: September 26, 2016

FDA okays first DMD drug

Sarepta wins approval for Duchenne muscular dystrophy treatment but must complete further studies
Department: Business
Keywords: rare disease, Duchenne muscular dystrophy, regulation, eteplirsen

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.

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Phosphorodiamidate morpholino oligomers are modeled after RNA but have different rings and linkages.
Credit: Sarepta Therapeutics
Chemical structure of phosphorodiamidate morpholino oligomer and RNA.
 
Phosphorodiamidate morpholino oligomers are modeled after RNA but have different rings and linkages.
Credit: Sarepta Therapeutics
 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society
Comments
Andy (Tue Sep 27 09:18:43 EDT 2016)
I think you got your morpholino structure wrong; highly doubtful that its held together through oxonium linkers
Elijah (Tue Sep 27 10:50:02 EDT 2016)
I am pretty sure the structure of the PMO as shown is incorrect, phosphamidate bond should be connected to a carbon attached alpha to the oxygen atom in the morpholine ring and not to the oxygen atom itself.
Sankha Pattanayak (Tue Sep 27 15:57:49 EDT 2016)
You are right Elijah. I also wonder what delivery moiety they have in the oligo.
Ann Thayer (Thu Sep 29 16:29:58 EDT 2016)
Yes, a mistake was made when drawing the structure -- the bond should be to the alpha carbon (to the left of the oxygen), not to the oxygen. Thanks for noticing. We plan to correct the structure.

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