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Dive Brief:
- In an unexpected decision, the Sarepta Therapeutics Drug Rejection for Duchenne Muscular Dystrophy, issued on Monday to a Complete Response Letter to the rare disease biotech.
- According to Sarepta, the agency cited in its refusal of infection is a precursor to the drug. Called Vyondys 53, the medicine is designed for approximately 8% of Duchenne patients with a specific genetic mutation.
- Shares in Cambridge, Mass.-Based Sarepta fell sharply in post-market trading. Approval of the drug was widely anticipated, making the rejection in Sarepta's ambitions to treat a wider pool of Duchenne patients.
Dive Insight:
Approval of Vyondys 53 (golodirsen) is considered to be safe given its similarities to Sarepta's marketed drug, Exondys 51 (eteplirsen), which is cleared for use in another subset of Duchenne patients.
Instead, Sarepta will need to avoid the risk of an excessive risk.
"The company is in charge of the issue of non-approvability of golodirsen, including the issues that formed the basis of the said company CEO Doug Ingram in a statement.
Neither Exondys nor Vyondys has results from a traditional placebo-controlled trial, but does not stop the FDA from controversially approving the trainer in 2016, overruling the recommendation of its own advisory panel in the process.
The two treatments known as exon-skipping, altering genetic expression to help patients produce a key-muscle building protein called dystrophin.
Missing exons in the code for the dystrophin gene. Sarepta's products aim to restore functional protein production by skipping the missing exon 51 in the box of Exondys and the missing exon 53 in the box of Vyondys.
A third drug, called casimersen and now about to face FDA review, skips exon 45, and if all three reach the market Sarepta should cover about 30% of DMD patients. SVB Leerink analysts had estimated the drugs of $ 1.7 billion by 2024, a lofty sum reflecting the lack of other treatment options for DMD patients currently.
This forecast would obviously be reviewed, and it would be expected that these conditions would be similar to Exondys.
According to Sarepta, the FDA's complete response to the risk of infection and the risk of infection are: The risk of infection at intravenous infusion ports, and kidney toxicity seen in pre-clinical studies of Vyondys and other antisense oligonucleotides, the class of drugs that includes Exondys and casimersen.
If so, what is the case?
In Vyondys' defense, Sarepta said: "Renal toxicity with golodirs was observed in pre-clinical models at doses that were ten-fold higher than the dose used in clinical studies. Renal was not observed in Study 4053-101, on which the application for golodirsen was based. "
The FDA apparently Exondys and now Vyondys – that of limited data on its effectiveness. In the case of Exondys, questions on the therapy's benefit so divided Robert Califf was called to the mediate the scientific dispute between staff.
For Vyondys, the company submitted to FDA results from a trial of 25 boys, all of which showed signs of exon 53 skipping. Mean dystrophin protein increased to 1.019% of normal, compared with 0.095% at baseline, after 48 weeks of treatment, at 10.7-fold increase.
Sarepta's six-minute walk test, but those have not been reported yet.
An analysis of DMD drugs done by the Institute for Clinical and Economic Review, which included Exondys, Vyondys and Emflaza (deflazacort), found there was little evidence that exon-skipping agents were superior to corticosteroids and supportive care. The increases in dystrophin production "are of uncertain clinical significance," the report said.
Sarepta said Monday that it would immediately request a meeting with FDA to determine its next steps for Vyondys. A study testing the drug alongside casimersen remains ongoing.
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