DMD is caused by a genetic defect that causes loss of dystrophin, an important protein associated with muscle repair and function. DMD patients can't produce dystrophin on their own, but in the eight boys treated with eteplirsen from the beginning of the study, dystrophin production increased 47% after 48 weeks. Dystrophin production also increased 38% in the four "delayed treatment" patients.
Much of the criticism leveled against the eteplirsen data to date has focused on small trial size (only 12 patients were enrolled) and the lack of walk benefit observed in the four DMD patients treated at the 30 mg dose. Two of the four patients became wheelchair bound soon after the study started, which didn't leave enough time for etelplirsen to work, Sarepta said.
Eteplirsen works by causing the body to "skip" a mismatched section of the exon (a sequence of nucleic acids) that codes for dystrophin. By skipping exon 51, the drug enables the creation of a semi-functional dystrophin protein.
"The eteplirsen trial included a very small number of patients but the counterpoint is that these are patients with a genetic defect that is being targeted precisely by the mechanism of action of this drug," said Dr. Alex Fleming, a former FDA drug reviewer who now runs Kinexum, a healthcare consulting firm. Fleming spoke about eteplirsen on an investor conference call last month organized by Summer Street Research Partners.
The ability of eteplirsen to produce functional dystrophin, which then translates into a real clinical benefit (improved walking performance), makes it easier for FDA to approve eteplirsen under the agency's existing regulations, added Fleming.
"Subpart H [accelerated approval] is designed to allow FDA to approve a drug based on surrogate outcomes. What we have with eteplirsen are data that go beyond encouraging production of dystrophin but also show patients walking a clinically meaningful longer distance. Theoretically, FDA could approve eteplirsen outright and not just under subpart H."
Cure Duchenne is another DMD non-profit group that has already met with FDA and is organizing a webinar later this month that will allow DMD families to ask questions of FDA officials. The webinar will also be a good opportunity for FDA to hear directly from people directly affected by DMD, says Cure Duchenne president Debra Miller.
"We are completely supportive of the DMD community and getting this drug [eteplirsen] approved," said Miller, also the mother of a boy with DMD. Miller says the actions being taking now by DMD advocates are laying the groundwork for more work to be done after Sarepta has its end-of-phase II meeting with FDA.
Sarepta shares closed Monday at $23.85.
-- Reported by Adam Feuerstein in Boston.