) -- Duchenne muscular dystrophy (DMD) advocacy groups are mobilizing to support efforts by
to seek accelerated approval for its experimental drug eteplirsen.
Some of these groups, accompanied by parents of DMD patients, have already met with U.S. Food and Drug Administration officials to make sure regulators understand the urgent need for new therapies. More meetings with U.S. regulators are planned.
Sarepta will meet with the FDA, likely early next year, to present results from the eteplirsen phase IIb study and request permission to file for accelerated approval. The company is holding a conference call Wednesday in conjunction with third-quarter financial results.
"We are absolutely going to do everything we can to get eteplirsen approved," said Sharon Hesterlee, senior director of research at Parent Project Muscular Dystrophy (PPMD), the largest DMD non-profit in the U.S.
In two meetings already held with the FDA's neurology division, Hesterlee says PPMD made sure the agency understands that "time is extremely critical" for DMD patients because the disease is relentlessly progressive. Every week and month that goes by means DMD patients lose more muscle function. Without treatment, DMD patients end up in wheelchairs and often die in their 30s.
"We made the point to FDA that we already know the risk of doing nothing in DMD. The risk tolerance for DMD patients is very high," says Hesterlee.
The Duchenne Alliance, an umbrella advocacy group that represents the interests of 37 smaller DMD charities and foundations worldwide,
submitted a dossier to FDA
last week to get DMD included on a list of rare diseases eligible for special considerations, including accelerated access and approval, under the recently approved "PDUFA V" legislation.
"We have such stellar, unprecedented data with eteplirsen. We really need to carry the flag on this," said Christine McSherry, Duchenne Alliance's executive director and the mother of a son with DMD.
After 48 weeks of treatment with eteplirsen at the highest 50 mg dose, four boys with DMD were able to walk 21 meters further than they could when the study started. Another four boys who started the study on placebo but then switched to eteplirsen after 24 weeks saw a stabilization of their walking ability, with six-minute walk test performance improving to a 68-meter decline at 48 weeks from a 78-meter decline at 36 weeks.
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.
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.
Adam Feuerstein writes regularly for TheStreet. In keeping with company editorial policy, he doesn't own or short individual stocks, although he owns stock in TheStreet. He also doesn't invest in hedge funds or other private investment partnerships. Feuerstein appreciates your feedback;
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