Parents Push One Rare-Disease Drug Through FDA, Not Its Successor

(Bloomberg Opinion) -- For a small biotechnology firm, Sarepta Therapeutics Inc. has made a lot of waves at the Food and Drug Administration. The 2016 approval of its first drug, Exondys 51 – which targets the deadly muscle-wasting disease Duchenne Muscular Dystrophy (DMD) – caused a schism at the agency. A highly organized and vocal group of parents and patients saw hope for boys otherwise resigned to a short and challenging life, helping it gain green-light status, while an agency detractor called the drug an “elegant placebo.” 

Sarepta’s second drug-approval attempt didn’t go so well. On Monday, the FDA rejected the company’s follow-up drug Vyondys 53, intended for another subset of DMD patients. According to the surprised company, the agency’s principal concerns were with infections related to ports used to infuse the drug, and kidney toxicity observed in pre-clinical models but not seen in the actual trial.

If those are the only problems, Vyondys could be back on track in relatively short order. But we don’t know if that’s all there is to it or whether there’s a simple fix because Sarepta didn’t share the FDA’s full rejection letter. The truth is, Sarepta may have a longer, rougher path to further FDA approvals than it previously thought, and its struggles could have a bearing on other drug developers in similar situations.

Vyondys likely won’t be approved until at least next year now. That’s not a deal-breaker; the drug was expected to contribute only a modest portion of Sarepta’s future sales. But analysts think the rejection could be about more than a few infections, which may be the reason the company’s shares plunged as much as 20% in early trading Tuesday. 

Royal Bank of Canada analyst Brian Abrahams suggested in a research note Tuesday that this decision may represent a backlash to Exondys’s approval. It also could be a signal that the agency is upping its safety bar in some cases. There may be something to that. 

Both Exondys and Vyondys appear able to produce tiny amounts of the protein that boys with DMD lack. It isn’t clear, based on Sarepta’s small trials, that this leads to a real-world benefit. Reliable confirmatory data may not arrive for years.

Advocates argue that the FDA should be biased toward approval, when there are no good options even if the data is somewhat scant. Exondys tested the limits of that argument, and it can cost as much as $1 million per year. Potential safety issues for such expensive therapies can make the push for approval harder to support.

In the case of Vyondys, the FDA appears to have dug pretty deep for a problem. But if Exondys was an exception and the agency continues to apply a higher standard through the inevitable criticism, another similar medicine of Sarepta’s in development called casamirsen could be in trouble as well.

Investors also have to decide if they need to worry about the company’s crucial next generation of drugs, which are gene therapies. Unlike Exondys, which needs to be dosed for years, these medicines could have a long-term impact after just one treatment. Sarepta has produced promising early results for its lead DMD gene therapy, and analysts expect it to generate a billion dollars in sales in 2021. 

There’s no direct relationship between Vyondys and the gene therapies; the latter work in an entirely different way and don’t have the same kind of efficacy questions. But they are still risky bets that rely on small trials and may require some degree of FDA flexibility.

The agency might be in an especially cautious mood in regards to gene therapies after a damaging data fracas recently related to a highly regarded drug made by Novartis AG. Any slowdown for Sarepta would give competitors including Pfizer Inc., Solid Biosciences Inc., and Audentes Therapeutics Inc. opportunities to catch up. 

At least a chunk of Sarepta’s multi-billion market  likely comes from the perception that it has the magic touch at a more flexible FDA. A previous strength may be turning into a weakness.

This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.

Max Nisen is a Bloomberg Opinion columnist covering biotech, pharma and health care. He previously wrote about management and corporate strategy for Quartz and Business Insider.

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