http://www.raredr.com/news/sarepta-debuts-golodirsen-data
Sarepta Debuts Golodirsen Data at World Muscle Society Meeting

Mathew Shanley

In September 2016, Sarepta Therapeutics received accelerated approval from the U.S. Food and Drug Administration (FDA) for its drug Exondys51 (eteplirsen).

The drug is intended to treat patients with Duchenne muscular dystrophy (DMD) amenable to exon 51-skipping therapy, however, concerns came form the general public regarding both the price of the drug and the quality of the data which led to its approval. Uncertainty about the therapy has been the impetus behind some insurance companies to refuse coverage of it until it is fully-approved.

With new data presented at the Annual Congress of the World Muscle Society in France last weekend, the biotech is checking off all the boxes to avoid a similar issue with its next drug, golodirsen (SRP-4053). The new therapy is intended to treat DMD patients amemable to exon 53-skipping therapy.

Sarepta released top-line results from its phase 1/2 muscle biopsy study last month, but provided more detail in a poster presentation authored by Francesco Muntani, M.D. of University College London at the France meeting.

DMD is a progressive degenerative muscle disease caused by low levels of the dystrophin protein. In the presentation, Muntani confirmed the boost in overall production of dystrophin provided by the drug in patients with DMD, and that the increase was seen in the sarcolemma – the area of muscle necessary for clinical benefit.

The low levels of dystrophin in DMD are the result of mutations along the Dystrophin gene, and without the dystrophin protein, which act as a shock absorber, muscles will eventually die. Symptoms typically begin to present in patients around 4- to- 5-years old and those suffering from the condition are commonly non-ambulatory by their teenage years.

Golodirsen shares the same phosphorodiamidate morpholino oligomer structure as eteplirsen, and the newly-presented data showed that all 25 subjects enrolled in the study experienced exon 53-skipping activity, making for a 100% response rate to the next-generation therapy.

Data for dystrophin and dystrophin mRNA were obtained from muscle biopsies taken at baseline and at week 48 from Part 2 of the study, when all patients were receiving 30 mg/kg/ week (Part A was a 12 week dose tritration study).

Using western blot analysis, dystrophin levels increased 10.7 fold from baseline to week 48. Simliarly, dystrophin mRNA with exon 53 skipped was increased 7.3 fold using reverse transcription polymerase chain reaction (RT-PCR).

Sarepta Therapeutics anticipates a meeting with the FDA regarding golodirsen in the first quarter of 2018, and hopes to experience similar financial successes to that seen by Exondys51. In addition to the revenue generated by the company’s last drug approved for the treatment of DMD, Sarepta was also granted a Rare Pediatric Disease Priority Review Voucher, which they flipped to Gilead Sciences in exchange for $125 million.

In early September after the release of the initial study data, Nasdaq reported that Sarepta shares were up 13.75%.

Reference:
Muntoni F, Frank D, Sordone V, et al. SRP-4053 induces exon skipping leading to sarcolemmal dystrophin expression in Duchenne muscular dystrophy patients amenable to exon 53 skipping. Presented at the 22nd International Annual Congress of the World Muscle Society; October 3-7, 2017, Saint Malo, France.

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