Sarepta Therapeutics announced initial positive results from its early-stage gene therapy program to treat a rare genetic form of muscular dystrophy called Limb-girdle muscular dystrophy (LGMD) that primarily affects the shoulders and hips. The gene therapy is one of five in development targeting this rare disorder.

The biotech announced the results at the same time that it said it had exercised its option to acquire Myonexus Therapeutics for $165 million. The companies had partnered less than one year earlier to develop Myonexus’ five LGMD gene therapies, which included an option for Sarepta to acquire the clinical stage Ohio-based biotech.

One of these gene therapies, MYO-101, was tested in a first in-human trial targeting children with LGMD2E, a rapidly progressing subtype that affects young children who begin showing neuromuscular symptoms such as difficulty running, jumping and climbing stairs before age 10. The disease progresses to loss of ambulation in the teen years, and often leads to death before age 30. There are approximately 19,000 LGMD patients in the United States and Europe, of which about 15 percent have LGMD2E. There is currently no treatment or cure for the disorder.

In the early-stage study, three patients, ages 4 to 13, were treated with a single infusion of Sarepta’s MYO-101, an engineered virus containing a healthy gene intended to transduce skeletal and cardiac muscle with a gene that codes for the full-length, native beta-SG protein, the lack of which causes LGMD. In biopsies taken at two months, all three participants showed robust expression of transduced beta-SG, properly localized to the muscle sarcolemma, as measured by immunohistochemistry. The pre-defined measure of success for expression in the study was 20 percent positive fibers. The actual mean protein expression, properly localized to the sarcolemma of the muscle, was 51 percent. Mean fiber intensity was 47 percent compared to the normal control.

All three patients also showed a striking decrease in serum creatine kinase (CK) levels from pre-treatment baseline measure to last measure, with a mean CK reduction of more than 90 percent from baseline. CK is an enzyme biomarker strongly associated with muscle damage.

Two patients had elevated liver enzymes, one of which was designated a serious adverse event, as the patient had associated transient increase in bilirubin. Both events occurred when the participants were tapered off oral steroids and, in both instances, elevated liver enzymes returned to baseline and symptoms resolved quickly following supplemental steroid treatment. There were no other clinically significant laboratory findings and no decreases in platelet counts were observed.

“Results in our first three clinical trial participants are consistent with what we have observed in preclinical models,” said Jerry Mendell, Curran-Peters Chair of Pediatric Research at Nationwide Children’s Hospital and lead investigator for the study. “We look forward to continuing this pivotal trial focused on development of MYO-101 for LGMD2E.”

Sarepta has more than 20 gene therapies in various stages of development, including five targeting Limb-girdle muscular dystrophy diseases, and others targeting Charcot-Marie-Tooth, MPS IIIA, Pompe, and other CNS-related disorders.

Photo: Jerry Mendell, Curran-Peters Chair of Pediatric Research at Nationwide Children’s Hospital

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