Bulls argue FDA will allow for accelerated approval because the drug is safe and tolerable. I'm the first to agree we need to get more medications to patients who have no other viable treatment options, but it would simply be unprecedented for FDA to award Sarepta accelerated approval on the basis of a faint and unclear efficacy signal from a small, open-label phase IIb study. DMD is a rare, orphan disease but the FDA holds these drugs to the same statutory requirements for demonstrating effectiveness and safety as regular drug applications.
When Sarepta unblinded the eteplirsen study at 24 weeks, the data collected after that time point became confounded with potential biases. The biases -- and the modest sample size -- render the data useless for the purposes of FDA determining substantial evidence of effectiveness or clinical benefit.
Sarepta bulls argue FDA will be swayed by DMD patients and their advocates demanding fast eteplirsen approval. But since when have federal agencies become so nimble and responsive to the emotional demands of the public? They haven't. While I have immense sympathy for families living with loved ones suffering from rare diseases, I look at the regulatory situation objectively, as will FDA.
Vyndagel for the treatment of transthyretin familial amyloid polyneuropathy (TTR-FAP), a rare and fatal disease, is an example of FDA's stoic position ensuring regulatory standards are upheld under all circumstances.The U.S. prevalence of TTR-FAP is only 2,500, yet Pfizer (PFE) still managed to submit a single multi-center, global, randomized, controlled study enrolling 128 patients as the basis for their submission. The drug was extremely well tolerated in the pivotal study with a placebo-like side effect profile. During the open public hearing session of an FDA advisory committee meeting to review the application in May 2012, patients, caregivers and advocates begged and pleaded with FDA directly to approve Vyndagel, citing specifically the drug's benign safety profile. FDA ignored these pleas and rejected Pfizer's Vyndagel application, requesting a second efficacy study be conducted to establish the drug's efficacy prior to an approval. More recently, patients and advocates suffering with chronic fatigue syndrome lobbied the FDA to approve Hemispherx Biopharma's (HEB) Ampligen. The agency received hundreds of letters, emails, and testimonies in support of Ampligen approval. One patient even went on a hunger strike, but to no avail. On Feb. 5, 2013, Hemispherx was issued a complete response letter citing insufficient safety and efficacy data to approve the product. When Sarepta meets with FDA this quarter, the company will show regulators eteplirsen data from a single-center study encompassing 12 patients. Blinded data from this study are only available up to 24 weeks, at which point there were no significant differrences in measures of efficacy between eteplirsen and placebo. FDA will also be presented data from the study taken after 24 weeks. These data are unblinded, exclude two patients from the active treatment arm and include a placebo group that was switched over to eteplirsen treatment. In my opinion, there is nothing adequate and well-controlled in these eteplirsen data. Evidence of efficacy is questionable due to bias. The small number of patients treated at limited eteplirsen doses are insufficent to assess safety comprehensively. In the extremely unlikely event FDA allows Sarepta to seek accelerated approval of eteplirsen, an FDA advisory committee would likely shoot the application down and demand more robust data prior to any approval. Disclosure: Chaudhry owns May puts in Sarepta. Follow Aafia Chaudhry on Twitter.