March 22, 2016
By Mark Terry, BioSpace.com Breaking News Staff
Thirty-six experts in Duchenne Muscular Dystrophy (DMD) signed a letter to the U.S. Food and Drug Administration (FDA) urging the regulatory agency to approve eteplirsen, a drug developed by Cambridge, Mass.-based Sarepta Therapeutics .
Originally the FDA’s Peripheral and Central Nervous System Advisory Committee was scheduled on Jan. 21 to make a decision on the company’s New Drug Application (NDA) for eteplirsen. However, due to an impending snowstorm on the east coast, the meeting was postponed. It is now scheduled for April 25.
There was some initial confusion over whether the drug had been turned down. On Jan. 14, the FDA rejected San Rafael, Calif.-based BioMarin Pharmaceutical Inc. ’s application for Kyndrisa (drisapersen) for DMD. The FDA argued that Kyndrisa didn’t show enough benefit. Because Sarepta’s meeting with the FDA was scheduled for the same period, some media outlets believed that the company’s drug had also been rejected, rather than a decision being postponed.
Also, on Jan. 26, Cambridge, Mass.-based Akashi Therapeutics announced that its clinical trial for HT-100 in DMD has been halted because one patient developed serious, life-threatening health problems. The patient was receiving the highest dose in the HALO trial, and the company has noted that no other patients showed the same problems.
DMD is a muscle-wasting disease caused by mutations in the dystrophin gene. It is a progressive disease and generally results in death in early adulthood. Serious complications include heart or respiratory-related problems. It affects mostly boys, about 1 in every 3,5000 to 5,000 male children.
The letter to the FDA was written by two co-directors of the Center for Duchenne Muscular Dystrophy at UCLA, M. Carrie Miceli and Stanley Nelson. Thirty-four additional doctors and scientists who specialize in DMD research from around the globe signed the letter, which was delivered to the FDA last month, but recently posted on the UCLA website.
The letter brings up two specific issues. The first was the question of whether the patients’ disease progression on eteplirsen substantially deviated from the expected course of the disease in a sufficiently reliable manner. The second question was, did the drug show “convincing evidence of dystrophin protein induction, the proposed mechanism of action of the drug?”
Noting the difficulty of conducting trials on DMD patients, and analyzing the unique conditions involved in this trial, the authors conclude that, “These three-year data alone are clearly supportive of accelerated approval, however the new four-year data regarding age at loss of ambulation now provide even more compelling data for accelerated approval based on an irreversible morbidity.”
They further say that, “We suggest that the most scientifically robust way forward and the most ethical choice for the Duchenne community is in the context of an accelerated approval followed by a confirmatory trial.”
Sarepta popped at the news. Shares traded for $14.55 on Mar. 16 and is currently trading for $21.71.
In February, 109 members of Congress also sent a sent a letter to the FDA urging it to accelerate approval of a DMD drug—any DMD drug, apparently, because no specific drug was mentioned in the letter.
Addressed to Janet Woodcock, director of the FDA’s CDER, the letter said, in part, “Consistent with FDA regulations, we believe it is ‘appropriate [for the FDA] to exercise the broadest flexibility in applying the statutory standards, while preserving appropriate guarantees for safety and effectiveness’ to new therapies intended to treat persons with life-threatening and severely-debilitating illnesses. As the FDA further notes, ‘the benefits of the drug need to be evaluated in light of the severity of the disease being tested.’ As Members of Congress representing constituents battling Duchenne, we wholeheartedly agree with this viewpoint and urge the FDA to ensure this flexibility is applied in reviewing all Duchenne candidate therapies.”
Although Sarepta’s eteplirsen has shown benefits in a Phase IIb trial, the biggest concern over previous studies is the size of the study, which is quite small. Also, the FDA seems to be reluctant to view increased dystrophin production as a completely valid endpoint to determine the drug’s effectiveness. The FDA is requiring Sarepta to run a bigger Phase III trial to confirm efficacy. Accelerated approval, as all these forces come together, is a real possibility, potentially by late May.
Sean Williams, writing for The Motley Fool, cautions investors to go in with their eyes fully open to the risks. “If eteplirsen is approved, it’ll likely carry a hefty specialty price tag and would go a long way to validating Sarepta’s exon-skipping drug development platform, which could treat nearly half of all exon-based DMD cases with eight developed medications. If eteplirsen fails, it could crush Sarepta shareholders’ ticket to easy money and leave the company reliant on its infectious disease portfolio.”
