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