Vyondys 53 Available to Duchenne Patients in the US – Muscular Dystrophy News

The newly approved therapyVyondys 53(golodirsen) is available for immediate distribution to treat people with Duchenne muscular dystrophy (DMD) amenable toexon 53 skipping, according to the medicines developer Sarepta Therapeutics.

In an email reply toMuscular Dystrophy News Today,a spokeswoman added that, similar toExondys 51(eteplirsen, also marketed by Sarepta), the price ofVyondys 53 will be based on a patients weight, with an estimated annual cost of $300,000 for a child weighing 20 kg (44 pounds).

Last week, the U.S. Food and Drug Administration (FDA) decided to conditionally approve Vyondys 53. The Phase 3 ESSENCE trial (NCT02500381), which is still recruiting, is now a post-marketing confirmatory trial, as is typically required by the FDA in conditional approvals.

People with DMD have impaired production of dystrophin, an essential protein for muscle integrity, due to mutations in the DMDgene.

Vyondys 53 is anexon-skipping therapy injected directly into the bloodstream. It is the first treatment intended for patients whose disease-causing mutations are in exon 53, which accounts for about 8% of all DMD cases. (Of note, exons are the tiny bits of DNA containing information to produce proteins.)

The treatment works by masking the mutated exon 53 in the messenger RNA generated from the DMD gene to produce a shorter but functional version of dystrophin.

The conditional approval came four months after the FDA rejected Sareptas first application due to two safety concerns: risk of infections related to infusion, and kidney toxicity seen in preclinical animal models though at doses 10 times higher than used in clinical trials, the company said.

After filing an appeal and meeting with FDA officials, Sarepta resolved the safety issues and resubmitted the application that was ultimately approved.

Full approval is now conditional on results seen in the ESSENCE study, expected to conclude by 2024. The trial was designed to evaluate the safety and effectiveness of Vyondys 53 and of casimersen (SRP-4045) an investigational exon-skipping therapy also by Sarepta in DMD patients with mutations amenable to exon 53 (Vyondys 53) or exon 45 (casimersen) skipping.

ESSENCE isenrolling up to 222 patients (111 patients in each of these groups) at sites across Canada and Europe, with locations in the U.S. yet to open. Its main goal is assessing changes in muscular strength and ability measured by the six-minute walk test after 96 weeks (almost two years) of treatment.

According to the company, safety of both therapies will be examined by analysis of adverse events (side effects), laboratory and medical tests (such as electrocardiograms), vital signs, and physical examinations. Sarepta also plans to assess safety through the collection of real-world data from patients treated with Vyondys 53.

To date, there were no signs of kidney toxicity and no safety issues prompting the interruption of ESSENCE, although a case of rhabdomyolosis (a syndrome related to muscle injury) led stopping the study in Europe, the Sarepta spokeswoman added.

Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.

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Jos is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimers disease.

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Vyondys 53 Available to Duchenne Patients in the US - Muscular Dystrophy News