Golodirsen

Golodirsen is indicated 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. ==Mechanism of action==

Golodirsen has been provisionally approved for approximately 8% of all people with Duchenne muscular dystrophy amenable to exon 53 skipping. It works by inducing exon skipping in the dystrophin gene and thereby increasing the amount of dystrophin protein available to muscle fibers. ==Adverse effects==

The most common side effects include headache, fever, fall, cough, vomiting, abdominal pain, cold symptoms (nasopharyngitis) and nausea. Although renal toxicity was not observed in the clinical studies with golodirsen, potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides. == Pharmacology ==

Pharmacokinetics Following single or multiple intravenous infusions, the majority of drug elimination occurs within 24 hours of intravenous administration. The elimination half-life of golodirsen, in parity with eteplirsen was 3 to 6 hours. ==Clinical benefits==

As a first-generation medication, golodirsen is far away from being curative; clinical trial outcomes have demonstrated it to have a marginal effect on ameliorating Duchenne muscular dystrophy pathology. As of December 2019, golodirsen is approved for therapeutic use in the United States, as well as in the countries that automatically recognize the decisions of the US Food and Drug Administration, under the condition that its benefit will be demonstrated in a confirmatory clinical trial. == Society and culture ==

Golodirsen is one of the very few FDA-approved exon-skipping therapy for Duchenne muscular dystrophy, although the clinical benefits of the medication are yet to established. While the development of golodirsen needed huge financing, it is only applicable to a small subset of people with Duchenne muscular dystrophy. Sarepta Therapeutics has announced that golodirsen will cost in parity with eteplirsen, another medication of a similar kind, which may be as high as per year. Also, the accelerated approval of golodirsen has paved the way for people to have early access to the medication, at the same time, it is shrouded with controversy over a number of issues. A double-blind placebo-controlled confirmatory trial (NCT02500381) is ongoing to resolve the issues. == History ==

Golodirsen was developed by collaborative research led by Prof. Steve Wilton and Prof. Sue Fletcher in the Perron Institute and licensed to Sarepta Therapeutics by the University of Western Australia. under the accelerated approval pathway. The application for golodirsen was granted fast track, priority review, and orphan drug designations, and a rare pediatric disease priority review voucher. == References ==