August 4, 2016
By Mark Terry, BioSpace.com Breaking News Staff
After the May 25 announcement that the U.S. Food and Drug Administration (FDA) was delaying its decision on approval of Sarepta Therapeutics ’ eteplirsen for Duchene Muscular Dystrophy (DMD), investors have been waiting often impatiently for news. Although neither the FDA nor Sarepta have said anything, company stock jumped when clinicaltrials.gov, the website that provides information about clinical trials, showed that the company’s Phase III ESSENCE trial for DMD had started recruiting patients.
DMD is a muscle wasting disease caused by mutations in the dystrophin gene. It is a progressive disease that usually causes death in early adulthood, with serious complications that include heart or respiratory-related problems. It mostly affects boys, about 1 in every 3,500 or 5,000 male children.
The story of Sarepta and eteplirsen has been a dramatic rollercoaster ride. In January, the FDA was scheduled to review the New Drug Application (NDA) for eteplirsen, but postponed it because of a pending snowstorm on the east coast. It was rescheduled for April 25.
In February, 109 members of Congress sent a letter to the FDA urging it to accelerate approval of a DMD drug, not specifying eteplirsen, but any DMD drug. In March, 36 DMD experts signed a letter to the FDA urging it to approve eteplirsen.
The April meeting was a media circus, lasting over 12 hours with 52 public commentators, often offering emotional pleas for help, including several boys with DMD and their parents.
The concerns over the drug focus primarily on the size of the clinical trial, which really only studied 12 patients with no control group. The majority of the FDA’s advisory committee didn’t believe the trial showed the drug worked. There has been an emphasis by the FDA and other scientific analysts that the drug may very well work—it’s shown promise—but that the trial hadn’t hit the bar of scientific validity that the FDA typically requires before approval.
“The data wasn’t there to approve on the basis of one poorly controlled trial,” said Caleb Alexander, a researcher at the Johns Hopkins Bloomberg School of Public Health, and chair of the advisory panel, at the time.
The FDA asked for more data. It would appear that the enrollment announcement is going to try and produce more and better data. Analysts with Leerink said in a note to investors, “We, however, remain skeptical of the ability to draw positive implications from this development and continue to believe the deck is stacked against Sarepta Therapeutics.”
Leerink continues to give Sarepta an “up” rating. Jarepta Capital repeated a “neutral” rating, saying they “would not be surprised” if eteplirsen received accelerated approval this month.
TheStreet, however, gave the company a “Sell” rating with a score of “D-.” “This is driven by a few notable weaknesses, which we believe should have a greater impact than any strengths, and could make it more difficult for investors to achieve positive results compared to most of the stocks we cover. The company’s weaknesses can be seen in multiple areas, such as its disappointing return on equity, weak operating cash flow, generally disappointing historical performance in the stock itself and poor profit margins.”
The Sarepta trial and eteplirsen has been an example of how controversial FDA decisions can be regarding hot-button emotional and political drugs. In essence, the FDA has been inclined to turn down eteplirsen on the basis of the science, but there has been significant pressure applied from Congress and the DMD community to approve the drug even if it works only a little bit. An article today written by BosCaptn on Seeking Alpha, starts by saying, “This is a detailed account of how the FDA lied and manipulated the public, the DMD community and the panelists during the Eteplirsen Advisory Committee (ADCOM) Meeting held earlier this year. The final FDA decision continues to be postponed at the cost of boys and their families.”
Yet there isn’t any explanation for why the FDA would do this. BosCaptn, who isn’t identified, goes on to say that the technical analysis of the FDA’s decision making that follows was made by “a group of about 18 people that came together using Twitter private group messaging to help fully understand the issue. It is a result of numerous and ongoing discussions to present the true facts of the situation.”
True or not, the analysis lacks much clout if it’s made by a group of unidentified people whose technical expertise and ulterior motives are not known or declared.
