Sarepta reports three-year study data for Duchenne muscular dystrophy drug eteplirsen

Sarepta Therapeutics announced Thursday long-term data from a Phase IIb study of the exon-skipping experimental therapy eteplirsen in patients with Duchenne muscular dystrophy (DMD), showing that through week 144, results on the 6-minute walk test (6MWT) demonstrated a decline in walking ability at a rate slower than would be expected based on available natural history data. The company noted that a continued stabilisation of respiratory muscle function was also observed.

CEO Chris Garabedian said "based on guidance from the [FDA] earlier this year, we plan to submit these results along with additional data and analysis as part of a new drug application for eteplirsen by year-end." Earlier this year, Sarepta disclosed plans to submit eteplirsen for approval in the US after receiving guidance on potential accelerated approval by the FDA. The agency had previously advised against seeking accelerated approval of eteplirsen, citing negative results from a Phase III study of Prosensa's similar drug drisapersen in DMD.

Study 202 included 12 patients who participated in Sarepta's earlier mid-stage Study 201, in which patients were randomised to receive treatment with one of two doses of eteplirsen or placebo for 24 weeks. In Study 202, which met its main goal of increased novel dystrophin as assessed by muscle biopsy at week 48, those patients given placebo in the earlier trial received one of two doses of eteplirsen. Results through week 144 showed that the six evaluable patients in the eteplirsen cohort experienced a decline in the maximum 6MWT distance of 32.2 metres versus baseline, compared to 107.4 metres for the four patients in the delayed-treatment cohort. Sarepta noted that the treatment benefit of 75.1 meters between the two groups was "significant," adding that after experiencing a decline of 68.4 meters from baseline to week 36, patients in the delayed-treatment cohort demonstrated a decline of 39.0 meters from week 36 to week 144, likely as a result of "meaningful" levels of dystrophin production.

"There has been a drop [in walking ability] for the treatment and placebo cohorts but nothing like what we see in the natural history studies of Duchenne," remarked Garabedian. However shares in Sarepta declined as much as 25 percent on the news, with some analysts noting that the declines in 6MWT distances were larger than expected. "We do not know if this decline is driven by just one patient or this was seen with all patients," commented Deutsche Bank analyst Robyn Karnauskas, adding "if this decline is across the board, there may be questions around the long-term efficacy of the drug." For related analysis, see ViewPoints: Investors spooked by most recent Sarepta data, but fears may be overblown.

Sarepta noted that data from all 12 patients illustrated that treatment with eteplirsen was associated with improvements of 14.7 percent, 12.8 percent and 11 percent in maximum inspiratory pressure, maximum expiratory pressure and forced vital capacity, respectively. The company said that these values compared to historical controls of 2.4 percent, -4.5 percent and -10.3 percent, respectively. "We are encouraged to see continued stability on measures of respiratory muscle function...for nearly three years," remarked Sarepta chief medical officer Edward Kaye. The executive noted that the drugmaker is "on track to initiate in the coming months several new clinical studies of eteplirsen in a broader patient population to further characterise the drug’s safety and efficacy profile."

Last month, Prosensa announced plans to seek marketing authorisation of drisapersen later this year in the US and EU. Meanwhile, in May, European regulators issued a positive opinion recommending conditional approval of PTC Therapeutics' DMD drug candidate Translarna (ataluren), reversing a previous negative opinion against conditional approval of the therapy.

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