Golodirsen


Golodirsen, sold under the brand name Vyondys 53, is a medication used for the treatment of Duchenne muscular dystrophy in people who have a confirmed mutation of the dystrophin gene that is amenable to exon 53 skipping. Golodirsen is a form of antisense therapy.
The drug was developed by Sarepta Therapeutics. It works by inducing exon skipping in the dystrophin gene and thereby increasing the amount of dystrophin protein available to muscle fibers.
The most common side effects reported by participants receiving golodirsen in clinical studies were headache, fever, cough, vomiting, abdominal pain, cold symptoms and nausea.
No clinical benefit of using golodirsen has been established. As of December 2019, golodirsen is approved for therapeutic use in the United States, as well as in the countries that automatically recognise the decisions of the US Food and Drug Administration, under the condition that its benefit will be demonstrated in a confirmatory clinical trial. It remains an experimental molecule elsewhere.

Pharmacokinetics and toxicity

In the pivotal clinical trial of golodirsen, dystrophin levels increased, on average, from 0.10% of normal at baseline to 1.02% of normal after 48 weeks of treatment with the drug or longer. The change was a surrogate endpoint and the trial did not establish clinical benefit of the drug, including changes to subject's motor function.
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, skin irritation and skin peeling, have occurred in people who were treated with golodirsen.
Renal toxicity was observed in animals who received golodirsen. Although renal toxicity was not observed in the clinical studies with golodirsen, renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides. Renal function should be monitored in those taking golodirsen.

History

The U.S. Food and Drug Administration approved golodirsen in December 2019, under the accelerated approval pathway. The application for golodirsen was granted fast track designation, priority review designation, orphan drug designation, and a rare pediatric disease priority review voucher.