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Yet another company developing a drug for Duchenne muscular dystrophy suffered a setback as PTC Therapeutics disclosed yesterday that the Food and Drug Administration rejected its application for its experimental treatment. The move is also the latest disappointment for the small, but highly vocal patient advocacy community that is pushing the agency very hard to approve a drug for the rare disease.

The FDA sent the drug maker a so-called Refusal to File letter, which means its application to win marketing approval was insufficient to permit a substantive agency review. The disclosure triggered a big sell-off in PTC stock and, more broadly, prompted a renewed round of skepticism over whether the FDA will endorse any drugs to treat Duchenne muscular dystrophy.

In recent weeks, the FDA declined to approve a drug from BioMarin Pharmaceutical and released documents in advance of an advisory committee meeting scheduled for last month in which agency medical reviewers suggested a Sarepta Therapeutics treatment was unlikely to be approved. Sarepta, however, quickly provided additional information, prompting the agency to delay the meeting until May.


“FDA shows its teeth in DMD,” wrote Simos Simeonidis, an analyst at RBC Capital Markets, in an investor note this morning. And he then rattled off a summation of the most recent agency moves that underscore the cloud hanging over these treatments: “rejection, tough briefing documents, (and) now a Refuse to File” letter. “FDA has recently shown it will not approve drugs it does not believe work.”

Duchenne causes muscles in children to stop working and eventually results in death because they can no longer breathe. About 20,000 new cases, mostly in boys, are diagnosed each year, but no treatment currently exists.


The drugs under development attempt to produce higher levels of a needed protein called dystrophin. Without this protein, muscle fibers degenerate and voluntary movement becomes impossible. The Sarepta and BioMarin treatments target just 13 percent of the patient population with a gene mutation that causes the disease. The PTC medicine targets a different 13 percent of patients.

For now, Wall Street believes the outlook for the PTC medication is dim. Its drug, called ataluren, failed a Phase 3 trial that was designed to confirm the results seen in a subset of patients in a Phase 2 trial. And that earlier trial failed to meet its primary endpoint because the drug did not demonstrate that boys showed a statistically significant improvement in a six-minute walking test compared with a placebo.

This was the same slice-and-dice approach to parsing data that BioMarin took toward seeking FDA approval, prompting Simeonidis to write “we believe that ataluren will have a very difficult time getting approved in the US.”

This development only adds to the intrigue surrounding the Sarepta drug.

Earlier this week, Adam Feuerstein of TheStreet pointed to a paragraph in an FDA guidance document that he suggested might support agency approval of the medicine (see page 13). One possible interpretation, he wrote, is that the FDA delayed the meeting to May in order to address concerns and allow the drug to be approved.

To what extent such an interpretation is reasonable is hard to know. But the parents of children with Duchenne are not sitting idly by. Last week, two advocacy groups succeeded in convincing more than 100 members of Congress — both Republicans and Democrats — to write the FDA and implore the agency to approve the Sarepta drug.

In the letter, they urged FDA officials to consider what is known as the accelerated approval, which permits the agency to endorse a drug for an unmet medical need based on a surrogate endpoint, rather than a measure of a clinical benefit. For Duchenne, a surrogate endpoint would be measured by improvement in a six-minute walking test.

“This allows demonstrably safe therapies that treat an unmet medical need and appear to be efficacious, even with some uncertainty, to avoid the years of regulatory barriers and become accessible earlier to patients who otherwise have no other option,” the lawmakers wrote.

They added that “it is critical the FDA take into account the views and experiences of patients as part of the review process.” They pointed to a federal law passed in 2012 that requires the FDA to work more closely with patients. As we have previously noted, the agency used a regulatory guidance drafted by one advocacy group as a blueprint for recommendations on developing drugs for the disease.

One patient advocate is undeterred.

The news about PTC is “obviously very disappointing,” said Debra Miller, who heads CureDuchenne, an advocacy group that raises money to invest in drug makers that are developing products to combat DMD. “It increasingly seems that the FDA is not listening to the voice of patients and parents.

“While we appreciate the diligence of the FDA in reviewing and vetting new drugs, overwhelming real-life evidence should allow for approvals with postmarketing studies to confirm safety and effectiveness. We don’t yet know the reason for (the PTC Refusal to File letter), and we would not anticipate this will have an impact on Sarepta’s chance at accelerated approval.”

  • This administration’s track record for giving the go ahead for new drugs is not very good. Must not fit their ‘agenda’. If this drug had been for one of their select groups – .001% of the population who wanted to use a bathroom that they ‘identify with ‘ in their minds, but not with their bodies though THAT goes through because they are ‘progressive thinkers’.

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