Shares in Sarepta Therapeutics plummeted as much as nearly 50 percent Thursday after FDA briefing documents released ahead of an advisory committee meeting reiterated earlier concerns about the company's application for eteplirsen as a treatment for certain patients with Duchenne muscular dystrophy (DMD). Agency staff again raised issues surrounding trial data for eteplirsen, including the small number of patients tested, the drug's effectiveness and Sarepta's statistical analysis.
Following the initial staff review in January, which had been prepared for an advisory meeting that was later postponed and rescheduled for April 25, Sarepta provided additional data to the FDA to correct what it said were "key inaccuracies" in the agency's analysis. However, the FDA rejected the drugmaker's "characterisation of inaccuracies" of the original briefing document.
The company's filing is based largely on the strength of a Phase II study of eteplirsen in 12 patients with DMD amenable to exon 51 skipping, but FDA staff suggested the newly submitted data further increased concerns regarding the reliability of the findings. Specifically, agency reviewers argued that Sarepta overestimated the amount of dystrophin produced in response to treatment, and also expressed doubt about the company's attempt to use data from a retrospective historical control study of DMD patients to demonstrate the efficacy of eteplirsen.
FDA reviewers suggested that any potential benefits of eteplirsen are unlikely to be noticeable outside of a large placebo-controlled study, and also restated that while it "is prepared to be flexible with respect to a devastating illness with no treatment options, we cannot approve drugs for which substantial evidence of effectiveness has not been established."
Eteplirsen was granted a rare paediatric disease designation by the FDA as a potential treatment for patients with DMD who are amenable to exon 51-skipping therapy. Earlier this year, the US regulator rejected BioMarin Pharmaceutical's filing for the DMD therapy Kyndrisa (drisapersen), citing a lack of sufficient efficacy evidence. The agency later issued a refuse-to-file letter to PTC Therapeutics for an application regarding its investigational drug Translarna (ataluren) in nonsense mutation DMD. For additional analysis, see ViewPoints: BioMarin's bullish guidance may imply the end is near for Kyndrisa and ViewPoints: FDA rejects PTC's Translarna filing – moved goalposts or a failure to communicate?
Commenting on the latest FDA staff review for eteplirsen, RBC Capital Markets analyst Simos Simeonidis said the FDA "does not appear to be giving an inch to the arguments put forth" by Sarepta, but is actually "doubling down on the negative view of the data." Analyst Joseph Schwartz of Leerink Swann agreed, saying the company's case for eteplirsen was "strongly challenged and largely invalidated by the FDA." He noted that "the panelists were very critical" of BioMarin's proposed DMD treatment, "and we expect a similar level of scrutiny" for Sarepta.
For related analysis, see ViewPoints: Sarepta investors counting on a change of heart from FDA are left disappointed.
For analysis on DMD therapies, see also ViewPoints: With first wave of DMD agents in limbo, second wave coming into focus and Spotlight On: Will scrutiny of Duchene muscular dystrophy therapies extend to the EU?
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