Sarepta Eyes Key Test for Gene Therapy in Rare Muscular Dystrophy

The $165 million bet that Sarepta Therapeutics placed on the gene therapy programs of Myonexus Therapeutics is starting to pay off with more early but encouraging clinical data from the deal’s most advanced program—a potential treatment for a type of limb-girdle muscular dystrophy.

Currently no available treatments exist for any of the many subtypes of limb-girdle muscular dystrophy (LGMD). But with the new data Sarepta unveiled Monday, the Cambridge, MA-based company says it is ramping up for a planned pivotal study next year of an experimental gene therapy designed to treat an LGMD subtype called Type 2E.

Initially developed at the Abigail Wexner Research Institute at Nationwide Children’s Hospital in Ohio, the experimental therapy—a single intravenous infusion—is currently being evaluated in six children, age four to 13, who have significant symptoms of the disease. Sarepta (NASDAQ: [[ticker:SRPT]]) has been tracking three patients who received a lower dose more than a year ago and, more recently, three patients who received a higher dose.

The program, SRP-9003 (formerly MYO-101), is designed to boost production of a protein called beta sarcoglycan (beta-SG) that those patients lack. The absence of beta-SG causes progressive loss of muscle function, which can lead to heart or lung problems resulting in early death.

Results released Monday revealed that patients in the high-dose group had an average of 72 percent of muscle fibers with beta-SG, surpassing the 50 percent threshold the company had defined as success, as measured by muscle biopsies taken 60 days after the treatment. Those patients also made an average of 89 percent less of an enzyme called creatine kinase, a biomarker for muscle damage.

Sixty days after the lower-dose group was treated, the average percentage of muscle fibers with beta-SG found in those patients was 51 percent, handily beating the 20 percent threshold for success Sarepta set, the company said last year.

Sarepta also reported Monday that one year after receiving treatment each of those patients had improved on all functional measures for which they were being tracked, including the time it takes to climb four stairs or to rise from the floor. Given the progressive nature of the disease, which can lead to a loss of the ability to walk without help during the teen years, those results would be unlikely in a group of similar age patients with the condition, according to Sarepta.

“These data support the conclusion that the therapy is achieving its intended purpose, driving robust expression in the muscles where it is needed,” company president and CEO Doug Ingram said in a statement.

Complications in the high dose group were generally mild to moderate, the biotech said; one patient became seriously dehydrated as a results of vomiting three days following the infusion, a side effect that resolved after two days of treatment with medicines to control nausea and IV fluids, it reported.

Sarepta intends to select the final dose for its registration trial in the third quarter and to start the trial in 2021, according to an investor presentation.

The company’s shares closed just shy of $160 apiece Monday, up 7 percent compared to Friday’s closing price of $147.99 apiece.

In a note to investors, SVB Leerink analyst Joseph Schwartz said the data “positions [Sarepta] as a front-runner in the gene therapy race for muscle dystrophies.”

Schwartz noted that the program uses the same delivery vehicle, promoter (DNA that spurs the gene being delivered “on” or “off), and dosing regimen as SRP-9001, its investigational gene therapy for Duchenne muscular dystrophy. Roche last December put up a staggering $1.15 billion for the rights to that program outside of the US. The therapy is designed to boost production of a smaller version of the dystrophin gene called micro-dystrophin.

Sarepta has four additional gene therapy programs in development for other subtypes of LGMD, plus an option to license a fifth.