Positive results from MYO-101 gene therapy study for limb-girdle muscular dystrophy prompt Sarepta to exercise purchase option on Myonexus

Sarepta Therapeutics on Wednesday revealed that the limb-girdle muscular dystrophy type 2E (LGMD2E) gene therapy candidate MYO-101 induced positive responses in a Phase I/IIa study in three patients with the disease. "Our gene therapy constructs have now produced high levels of expression of the missing protein of interest, and strong results in related biomarkers, in [Duchenne muscular dystrophy] and LGMD2E," stated CEO Doug Ingram. Shares in the drugmaker rose as much as 10 percent on the news. 

In cohort one of the study, three children aged four years to 13 years received an infusion of MYO-101 at a dose of 5x1013 vg/kg, followed by biopsies taken after about two months. Preliminary results showed that all three patients exhibited "robust expression of transduced beta-sarcoglycan (beta-SG), properly localised to the muscle sarcolemma," Sarepta said. 

In particular, the mean transduced beta-SG protein expression in the sarcolemma was 51 percent, compared with a pre-specified measure of success of 20 percent, while the mean fibre intensity was 47 percent, compared to normal control. The company added that all participants showed "robust quantification" of beta-SG, as measured by Western blot, with mean beta-SG of 36.1 percent of normal control, coming in above analyst expectations for 20 percent expression or more. Meanwhile, Sarepta noted that all participants exhibited a "striking decrease" in serum creatine kinase levels, with reductions of more than 90 percent on average versus baseline, topping analyst forecasts of more than 50 percent. 

Two of the participants experienced elevated liver enzymes, categorised as serious in one person, which company officials attributed to the steroids that were administered at the end of the trial. Louise Rodino-Klapac, Sarepta's vice president of gene therapy, noted that the rise in liver enzymes the participant experienced subsided with supplemental steroid doses, while Ingram said "it does appear to be a sort of transient issue that's well managed with the use of steroids." Sarepta is planning to dose a total of nine patients in the study.

MYO-101, which Sarepta is developing with Myonexus Therapeutics as part of a deal reached last year, uses the AAVrhm74 vector to facilitate targeted delivery of the therapy to skeletal, diaphragm and cardiac muscle "without promiscuously crossing the blood-brain barrier," as well as the MHCK7 promoter to ensure robust expression in the heart. "The results are a validation that we have the right approach to bring a better life to patients affected by these rare diseases," commented Ingram.

Separately on Wednesday, Sarepta announced that it exercised an option to acquire Myonexus, gaining full rights to MYO-101 and four other experimental gene therapies to treat distinct forms of limb-girdle muscular dystrophy, including MYO-102 for LGMD2D, MYO-103 for LGMD2C, MYO-201 for LGMD2B and MYO-301 for LGMD2L. Sarepta will pay the latter's shareholders $165 million under the deal. 

Ingram said that the results from the study for MYO-101 made it a "compelling time" for Sarepta to take control of Myonexus, as well as its other assets. "The five LGMD gene therapies being developed fit brilliantly with Sarepta's mission to develop therapies with the potential to rescue the lives of patients with serious life-limiting rare genetic diseases," Ingram said. He added that the MYO-101 "results have potential read through to our other four LGMD programmes and further validate our gene therapy approach." Ingram indicated that Sarepta plans to meet with the FDA discuss the next steps for the five limb-girdle muscular dystrophy programmes.

Meanwhile, Sarepta also reported fourth-quarter results Wednesday, with Duchenne muscular dystrophy drug Exondys 51 generating sales of $84.4 million. Analysts were expecting the therapy to record revenue of about $85 million for the three-month period. 


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