In an About-Face, FDA Approves Second Sarepta Muscular Dystrophy Drug

Xconomy Boston — 

Sarepta Therapeutics received an early holiday gift Thursday—approval of golodirsen (Vyondys 53), its second Duchenne muscular dystrophy treatment, which the FDA rejected in August.

The agency had dinged the application over potential side effects, namely a risk of infections from the “ports” used to infuse the drug, and kidney problems observed in animals in which golodirsen and other RNA-based drugs like it were tested.

Sarepta (NASDAQ: SRPT), at the time, said it was “very surprised” by the rejection, and that the FDA hadn’t previously raised any issues about those side effects. Doug Ingram, CEO of the Cambridge, MA, biotech, said the company would ask to meet with agency representatives to determine next steps.

In a prepared statement Thursday, Ingram said the company formally appealed the decision, the issues raised were “rapidly evaluated and resolved,” and Sarepta had resubmitted its application. How exactly the issues were resolved is unclear. The FDA said in its announcement of the approval that while the kidney issues it had noted in animal tests didn’t occur in Sarepta’s trials, the renal function of patients who receive the drug should be monitored.

Sarepta’s golodirsen is intended to slow the progression of the progressive, fatal disease, in a subset of patients—about 8 percent of those with the disease—by increasing patients’ levels of dystrophin, a protein needed for muscle function. Patients with Duchenne have a genetic mutation that prevents them from making dystrophin, causing motor function.

In 2016, an advisory board to the FDA recommended that the agency reject Sarepta’s first Duchenne drug, eteplirsen (Exondys 51), which was developed for another subgroup of Duchenne patients, concerned that the evidence supporting the drug was insufficient. Sarepta made its initial case for eteplirsen based on 10 patients’ continued ability to walk after taking the drug for about four years. Later that year the FDA bucked the advisory guidance and approved eteplirsen based on new data from more patients showing the drug was helping them produce dystrophin.

No such advisory meeting was scheduled in connection with golodirsen, which contributed to the shock over the agency’s August rejection.

Sarepta’s golodirsen studies tracked its impact on dystrophin expression in 25 boys. (Duchenne affects about 300,000 people worldwide, almost all boys, most of whom die from respiratory or heart failure by age 30.) Whether the drug raises patients’ dystrophin levels is considered a “surrogate” endpoint, or a likely predictor, but not evidence of clinical benefit.

Like it did with Exondys, the FDA approved golodirsen on an “accelerated” basis, a quicker review based on less evidence than is typically required. To keep the approval, Sarepta must provide more data. The post-marketing clinical trial is already underway. But results won’t be available for years; it is anticipated to end in 2024.

Sarepta said it would immediately begin commercial distribution of golodirsen in the US. It is pricing the drug at parity with its first Duchenne drug.

SVB Leerink’s Joseph Schwartz said in a note to clients that given the golodirsen approval, the firm now gave casimersen, the next Duchenne drug in the Sarepta pipeline, a 70 percent chance of a nod from the FDA, up from 50 percent.