Copied
Interesting Case Study . Can something like this happen for Mesoblast? see below
In stunning reversal, FDA clears Sarepta DMD drug it rejected 4 months ago
by Angus Liu
The FDA’s attitude toward Sarepta Therapeutics’ Duchenne muscular dystrophy (DMD) therapies is nothing short of dramatic. In just four months, the agency shocked industry watchers twice, first with a rejection and now a reversal for the biotech’s Exondys 51 follow-on.
Out of nowhere, the agency Thursday granted accelerated approval to Sarepta’s Vyondys 53 (golodirsen), a drug it turned down in August for safety reasons. The go-ahead covers about 8% Duchenne patients whose dystrophin gene bears a certain mutation amenable to exon 53 skipping.
While the FDA didn’t elaborate on the sudden change of course, Sarepta said it had launched a formal dispute resolution request after receiving the agency's complete response letter (CRL) detailing its reasons for the rejection. Sarepta worked with Peter Stein, director of the FDA's Office of New Drugs, to resolve the concerns raised in that CRL.
In August, a stunned Sarepta said the FDA had rejected Vyondys 53 for the risk of infection linked to intravenous infusion ports and for kidney toxicity seen only in animal studies. Analysts suspected at the time that the agency had changed its standards on using dystrophin as a surrogate marker for approval. DMD patients lack dystrophin, a protein that helps maintain the structure of skeletal muscle fibers, due to missing exons in the DMD gene.
Controversy erupted in 2016 when Sarepta’s Exondys 51 won an FDA thumbs-up based on dystrophin data without showing actual clinical benefits such as improvement on disease progression. Opinions were split even within the FDA; in fact, two officials who'd opposed the green light decided to retire. In contrast, European regulators shot down Exondys 51 last September—for the second time.
Like Exondys 51, Vyondys 53 was approved based only on dystrophin production “that is reasonably likely to predict clinical benefit” in DMD patients, the FDA said in a statement—not on proven clinical improvements. In a small clinical trial, 25 patients on Vyondys 53 saw 1.02% of normal dystrophin production after 48 weeks of treatment, up from 0.1% at baseline.
Expand
(20min delay)