FDA Approves First Drug for Duchenne Muscular Dystrophy
This morning the FDA announced its approval of eteplirsen (brand name, Exonys 51) for the treatment of Duchenne muscular dystrophy (DMD) in boys “who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping.” The drug was given the nod under the FDA’s accelerated approval pathway and largely on the basis of a surrogate endpoint: the production of dystrophin in DMD-affected muscles. Although, the FDA warned, the drug has not yet demonstrated associated clinical benefit.
The FDA has concluded that the data submitted by the applicant demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit in some patients with DMD who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping.
A condition of the FDA’s approval is that the drug manufacturer, Cambridge-based Sarepta, conduct a trial to show clinical benefit; however, the FDA did not dictate the particulars of the trial in today’s statement. If a blinded, randomized, placebo-controlled trial is required, Sarepta may have difficulty finding boys who are willing to chance an assignment to placebo.
The FDA’s approval also came with a Priority Review status (and, presumably, a very valuable Priority Review Voucher), as well as an orphan drug designation (and presumably, the hefty drug price that usually goes with it).
For brief background on the contentious FDA advisory committee meeting regarding eteplirsen, see STAT’s write-up. Sarepta’s share price shot up mightily on the news of eteplirsen’s approval this morning (80% as of this post).
I, for one, hope that the use of eteplirsen in DMD—particularly early use in young boys—will show unequivocal clinical benefit, beyond that conceivable with placebo. Furthermore, it is hoped that eteplirsen’s proof-of-concept will bolster development of other exon-skipping drugs for DMD and other amenable conditions.
Update from Jessica Adams on Twitter: The required 2-year, randomized, double-blind trial will not require a placebo-treatment arm. One arm will consist of the FDA-approved dosage of eteplirsen (30 mg/kg/week). Another arm will expose enrollees to a higher dosage (eg, 30 mg/kg/day). The primary endpoint will be the North Star Ambulatory Assessment.
— Jessica Adams (@RxRegA) September 19, 2016