Megan Brooks

The US Food and Drug Administration (FDA) has approved golodirsen injection (Vyondys 53, Sarepta Therapeutics), the first treatment for Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation amenable to exon 53 skipping.

Last summer, the agency declined to approve of the drug on an accelerated basis, sending a complete response letter (CRL) to the company citing concerns over the risk for intravenous infusion-port infections and the possibility of renal toxicity, as reported by Medscape Medical News.

Shortly thereafter, Sarepta filed a formal dispute resolution request with the FDA and the matters raised in the CRL were evaluated and resolved by the FDA Office of New Drugs (OND), the company said in a news release announcing approval.

Golodirsen is an antisense oligonucleotide that uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to bind to exon 53 of dystrophin pre-mRNA, resulting in exclusion, or “skipping,” of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 53 skipping.

The indication for golodirsen is based on a statistically significant increase in dystrophin production in skeletal muscle seen in treated patients, which is “reasonably likely to predict clinical benefit for those patients who are exon 53 amenable,” the company explains.

A postmarketing confirmatory trial called ESSENCE is currently enrolling patients and is expected to conclude by 2024.

Hypersensitivity reactions, including rash, pyrexia (fever), pruritis, urticaria, dermatitis, and skin exfoliation have occurred in patients treated with golodirsen. Renal toxicity was observed in animal studies.

The most common adverse reactions that occurred in at least 20% of patients treated with golodirsen and more frequently than in placebo-treated patients were headache, pyrexia, fall, abdominal pain, nasopharyngitis, cough, vomiting, and nausea.

In 2016, as reported by Medscape Medical News, the FDA approved the first drug for DMD, Sarepta’s eteplirsen (Exondys 51), indicated for patients with a confirmed mutation of the dystrophin gene amenable to exon 51 skipping.

“Along with Exondys 51 (eteplirsen), we now offer treatment options for approximately 20% of those with DMD in the US,” Doug Ingram, Sarepta president and CEO, said in a statement.