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FDA Greenlights New Duchenne Drug

— Golodirsen, rejected in August, is now approved

Ƶ MedicalToday
golodirsen (Vyondys 53) over a photo of a teen male in a wheelchair on the beach above FDA APPROVED

WASHINGTON – The FDA granted (Vyondys 53), an injection to treat Duchenne muscular dystrophy (DMD) patients who are amenable to exon 53 skipping. About 8% of DMD patients have the mutation targeted by golodirsen, the agency noted.

The green light comes 4 months after the the drug, citing concerns about infusion ports infections and renal toxicity seen in preclinical studies.

"In the span of four months, we commenced and completed the formal dispute resolution process culminating in the grant of our appeal, resubmitted our New Drug Application and obtained an approval -- a great benefit to DMD patients awaiting treatment," Sarepta's president and chief executive officer, Doug Ingram, said in a .

Golodirsen is Sarepta's second approved exon-skipping RNA therapy for DMD; the first was eteplirsen, (Exondys 51), approved in 2016. In the controversial decision to approve eteplirsen, the FDA overruled its own advisory committee.

With golodirsen and eteplirsen, "we now offer treatment options for approximately 20% of those with DMD in the U.S.," Ingram said.

Duchenne muscular dystrophy is caused by an absence of dystrophin. First symptoms of DMD are usually seen when patients are ages 3 to 5 years and worsen over time. People with DMD progressively lose the ability to perform activities independently and often require a wheelchair by their early teens; as the disease progresses, life-threatening heart and respiratory conditions can occur.

Golodirsen, an antisense oligonucleotide, won approval through the FDA's for drugs that treat serious or life-threatening diseases and generally offer a meaningful advantage over existing treatments. Under this pathway, approval can be based on studies that show a drug has an effect on a that is likely to predict clinical benefit.

In this case the surrogate outcome measure was skeletal muscle dystrophin production. In the main trial underpinning the approval, 48 weeks of treatment was associated with an average 10-fold increase in this marker, the FDA said. As part of the accelerated approval process, the FDA is requiring a clinical trial to assess whether golodirsen improves motor function. The placebo-controlled trial currently is enrolling patients and is expected to conclude by 2024, Sarepta said.

The most common side effects reported by participants receiving golodirsen in clinical studies were headache, fever, cough, vomiting, abdominal pain, cold symptoms, and nausea. Hypersensitivity reactions, including rash, fever, itching, hives, dermatitis, and skin exfoliation also have occurred.

Kidney toxicity has been seen in animals who received golodirsen. While not observed in the golodirsen clinical studies, renal toxicity, including potentially fatal glomerulonephritism, has been detected after certain other antisense oligonucleotides have been administered.

Golodirsen is priced at parity to eteplirsen, Sarepta said. An in May looked at the cost effectiveness of eteplirsen, golodirsen, and Emflaza, a corticosteroid used to treat DMD, and concluded that "underlying evidence for evaluating the cost-effectiveness of treatments in DMD remains sparse."