FDA Denies Approval for Duchenne Muscular Dystrophy Drug

Deborah Brauser

August 20, 2019

The US Food and Drug Administration (FDA) has nixed approval of golodirsen injection (Vyondys 53, Sarepta Therapeutics) for the treatment of Duchenne muscular dystrophy (DMD), according to a statement from the manufacturer.

The FDA's complete response letter (CRL) to the treatment's New Drug Application cites concerns over the risk for intravenous infusion-port infections and the possibility of renal toxicity.

However, this type of toxicity "was observed in pre-clinical models at doses that were ten-fold higher than the dose used in clinical studies," the company said in a press release. "Renal toxicity was not observed in Study 4053-101, on which the application for golodirsen was based."

Doug Ingram, president and CEO of Sarepta, noted in the same release that the company was "very surprised" to have received the CRL.

"Over the entire course of its review, the Agency did not raise any issues suggesting the non-approvability of golodirsen, including the issues that formed the basis of the complete response letter," Ingram said.

He noted that the manufacturer will work toward addressing the issues in order to find "an expeditious pathway" toward future approval of the drug — and will be requesting an immediate meeting with the FDA.

"We know that the patient community is waiting," said Ingram.

Rocky Road

The manufacturer was seeking accelerated approval of the drug for the treatment of patients with DMD and who have a "confirmed mutation amenable to exon 53 skipping."

The company based its current application on study 4053-101. According to Sarepta's website, this phase 1/2 study had a randomized, double-blind, placebo-controlled-dose-titration part 1 and then open-label efficacy and safety evaluation in its part 2.

Interestingly, the global, phase 3 randomized controlled trial ESSENCE (Study 4045-301) is ongoing and is examining the safety and efficacy of both golodirsen and of casimersen, "our exon-45 skipping agent," vs placebo, according to Sarepta.

As reported by Medscape Medical News, the FDA gave accelerated approval in 2016 to the first DMD drug, Sarepta's eteplirsen (Exondys 51 ).

That decision was controversial, as the FDA's Peripheral and Central Nervous System Drugs Advisory Committee concluded 5 months earlier that evidence of the drug's efficacy was not persuasive (the vote was 7-3, with three other committee members abstaining). Two years later, European Medicines Agency's Committee for Medicinal Products for Human Use gave a negative opinion for the treatment.

Follow Deborah Brauser on Twitter: @MedscapeDeb . For more Medscape Neurology news, join us on Facebook and Twitter


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.