Investigational Limb-Girdle Muscular Dystrophy Treatment Shows Promise at 9 Months


New 9-month data suggest that Sarepta Therapeutics’ investigational limb-girdle muscular dystrophy type 2E treatment, SRP-9003, is linked to improved functional measures and reduction in creatine kinase.

Dr Jerry Mendell

Jerry Mendell, MD, principal investigator at the Center for Gene Therapy in the Abigail Wexner Research Institute at Nationwide Childrens Hospital

Jerry Mendell, MD

Investigational limb-girdle muscular dystrophy type 2E (LGMD2E) treatment SRP-9003 has shown success in a small clinical trial of 3 patients, according to 9-month results announced by Sarepta Therapeutics.

SRP-9003, a gene therapy intended to transduce skeletal and cardiac muscle with a gene that codes for the full-length, native beta-sarcoglycan protein, was associated with improvements in functional measures and a maintained significant reduction in creatine kinase.

“LGMD2E is a devastating neuromuscular disease with no current treatment options so we are very pleased to observe a functional improvement in study participants who received SRP-9003,” said Jerry Mendell, MD, principal investigator at the Center for Gene Therapy in the Abigail Wexner Research Institute at Nationwide Children’s Hospital and lead investigator for the study, in a statement.

The study results were similar to the positive and robust expression and biomarker data Sarepta presented earlier this year. In this first cohort, patients aged 4 to 13 years were treated with an infusion at a dose of 5x1013vg/kg, with these measures observed at day 270.

“We have now observed consistent functional improvements, in addition to high levels of expression of the missing protein of interest and strong results in related biomarkers, in both of our first cohorts for Duchenne muscular dystrophy (SRP-9001) and LGMD2E (SRP-9003),” Doug Ingram, president and chief executive officer, Sarepta, said in a statement. “We intend to test one higher dose of SRP-9003 in LGMD2E participants, select our clinical dose and then advance our SRP-9003 program, along with our other 5 LGMD programs, as rapidly as possible.”

At the 9-month mark, all 3 participants had improvements from baseline in the North Star Assessment for Dysferlinopathy (NSAD), time to rise, 4-stair climb, 100-meter walk test, and 10-meter walk test scores, with results which were distinct from what an age-matched, natural history group would predictably show. As well, creatine kinase, the enzyme biomarker strongly associated with muscle damage, was significantly reduced.

Natural history patients with LGMD2E begin showing neuromuscular symptoms such as difficulty running, jumping, and climbing stairs prior to age 10. LGMD2E is an autosomal recessive subtype of LGMD which progresses to loss of ambulation in the teenage years and often death prior to age 30; there is currently no available treatment.

In this cohort, SRP-9003 showed no new safety signals, with its safety profile to date supporting dose escalation in the next cohort of the study. As previously noted, 2 patients in the study had elevated liver enzymes. One was designated a serious adverse event (AE) due to associated transient increase in bilirubin, but both events occurred when the participants were tapered off oral steroids and elevated liver enzymes ultimately returned to baseline and symptoms resolved following supplemental steroid treatment.

“With the results of our first LGMD2E cohort, Sarepta continues to build its gene therapy engine, an enduring model created to design, develop and bring to the medical and patient community transformative therapies for those living with, and too often dying from rare genetic disease,” Ingram said.

Sarepta had previously shared expression results from the study, which found that in 2-month post-treatment muscle biopsies, clinical trial participants showed a mean of 51% beta-sarcoglycan positive fibers, as measured by immunohistochemistry (IHC), substantially exceeding the pre-defined 20% measure for success. Mean fiber intensity compared to normal control was 47%, as measured by IHC.


Sarepta Therapeutics Announces Positive Functional Results from the SRP-9003 (MYO-101) Gene Therapy Trial to Treat Limb-Girdle Muscular Dystrophy Type 2E, or Beta-Sarcoglycanopathy [press release]. Cambridge, MA: Sarepta Therapuetics; Published October 4, 2019. Accessed October 4, 2019.

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