CAMBRIDGE, Mass. (TheStreet) -- Duchenne muscular dystrophy is a progressive disease that causes patients to lose muscle function over time. None of the therapies being developed today to treat Duchenne are curative, so the best these still-experimental drugs will do is slow the progression of the disease and give the kids more time outside a wheelchair.
I bring up this reminder about the inevitable muscular deterioration seen with Duchenne because the walking ability of patients treated with Sarepta Therapeutics' (SRPT) experimental drug eteplirsen declined greater at 144 weeks than in previous updates from the phase II study.
Sarepta briefed me on the new eteplirsen phase II study results Wednesday, embargoed until the announcement was made public Thursday morning.
After almost three years, the six Duchenne boys treated with eteplirsen from the beginning of the study reported a maximum loss of 32.2 meters, or about 8.5%, from baseline walking ability, as measured by the six-minute walk test.For the four Duchenne boys who began the study on placebo but switched over to eteplirsen six months later, the maximum loss of walking ability at 144 weeks was 107.4 meters, or 27%, compared to their baseline. All 10 boys across both arms of the study -- with an average age of 12 years -- can still walk on their own and only two of the boys have lost muscle function to the point where their score on the six-minute walk test is below 300 meters, said Sarepta CEO Chris Garabedian, in a phone interview. "There has been a drop [in walking ability] for the treatment and placebo cohorts but nothing like what we see in the natural history studies of Duchenne," said Garabedian. "These boys are still doing well relative to their age and where they started with their disease progression." Sarepta shares have been under steady selling pressure for the past week, based on anecdotal reports of eteplirsen patients deteriorating and general investor worries that the drug's benefit may be waning. Sarepta shares closed Wednesday at $25.89. Nearly all of the stock's gains made in April -- when the company surprised investors with plans to seek early U.S. approval for eteplirsen -- have disappeared. Even if it's unrealistic to have believed eteplirsen (or any drug in development today) could halt the progression of Duchenne forever, Sarepta's 144-week update looks different than the company's previous study updates. As a reminder, the six eteplirsen-treated boys reported a maximum decline of 14 meters in walking ability after 120 weeks, compared to the 39-meter decline reported today at 144 weeks, or six months later. For the placebo/delayed eteplirsen patients, the equivalent decline in walking ability over the last six months went from 79 meters to 107 meters. In both arms of the study, the rate of decline in walking performance accelerated over the past six months compared to the relative stability seen in the year prior. "It's a lot to expect we would halt the disease in its tracks, but if you look at the slope of the [six-minute walk test] curves, the boys in both arms of the study have a lot of ambulation ahead of them... The data support a treatment benefit for eteplirsen," said Garabedian.
I was unable to speak with Dr. Jerry Mendell, a noted Duchenne expert at Nationwide Children's Hospital in Columbus, Ohio and the lead investigator in the eteplirsen phase II study, but in a statement provided by Sarepta, Mendell said, "The long-term clinical data for eteplirsen showing a slowing in the decline of walking ability in a population now on average 12 years old are very encouraging, particularly when compared with the growing body of DMD natural history data which clearly show that similarly aged patients typically experience an increasingly rapid decline in walking ability and lose ambulation in their early teen years." The walk data are backed up by pulmonary muscle test results, also updated through 144 weeks, which show continued increases in lung function compared to baseline. The lung function data include the two boys enrolled in the study who quickly lost the ability to walk and were excluded from the analysis of six-minute walk test. Aside from the 144-week update, Garabedian says Sarepta is still on track to dose the first ambulatory Duchenne patient in the planned, confirmatory, phase III study of eteplirsen before the end of the third quarter. The eteplirsen FDA approval submission is also still on target for an end-of-year filing. No decision has been made about performing a fourth muscle biopsy on the boys in the phase II study to provide further data on dystrophin production, although Sarepta would like this to happen, Garabedian said. Prosensa (RNA) recently announced plans to submit its own Duchenne drug drisapersen to the FDA "later this year" based on mixed clinical data, including a phase III study which failed to show any treatment benefit for the drisapersen. This sets up a likely scenario where FDA will convene an advisory committee meeting in early to mid 2015. The invited experts on the committee will review both eteplirsen and drisapersen and vote on whether or not to recommend their respective approvals.
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