• An experimental gene therapy showed early signs of working in three patients with limb-girdle muscular dystrophy, spurring increased expression of a crucial protein missing in individuals with the rare, genetic neuromuscular disorder.
• Results were disclosed Wednesday by Sarepta Therapeutics, which has been developing the gene replacement therapy in partnership with Myonexus Therapeutics. While preliminary, the data gave Sarepta enough confidence to exercise an option to buy Myonexus outright in a $165 million deal also announced Wednesday.
• The therapy, which delivers a gene that encodes for the needed protein, is the second treatment advanced by Sarepta to show promise for treating a genetic neuromuscular disease. The biotech has also reported positive results for a gene therapy aimed at Duchenne muscular dystrophy. Both therapies come from research conducted at Nationwide Children’s Hospital in Ohio.

Much of the attention paid to Sarepta has centered on its work in Duchenne muscular dystrophy, a muscle-wasting disease that primarily affects boys. Last fall, results from four DMD patients treated with Sarepta’s gene therapy reinforced earlier signs of promise, suggesting the treatment could potentially alter the course of the disease.

​The biotech’s gene therapy ambitions, though, stretch broader. Wednesday’s data were the first substantive look at whether Sarepta could follow success in DMD with progress in another muscular dystrophy.

Unlike DMD, limb-girdle muscular dystrophy affects males and females equally. Triggered by a defect in a single gene, the disease causes progressive muscle weakening beginning in the hips and shoulders before affecting muscles in the arms and legs. Symptoms usually start to emerge before the age of 10 and it is often fatal before age 30.

MYO-101, as Sarepta’s therapy is called, aims to check — and potentially reverse — that progression by delivering a functional gene to skeletal, diaphragm and heart muscles via a viral vector. With a functional gene in place, the hope is patients will begin to express a missing protein behind limb-girdle muscular dystrophy.

The three patients, who ranged in age from four to 13, were all treated with 5x13vg/kg​ dose of MYO-101. That dose is lower than what Sarepta’s used in its DMD gene therapy program.

Biopsies taken two months after treatment showed mean protein expression of 51% — well above the 20% expression level predefined as a measure of success. By Western blot, a second measure of evaluating expression, mean protein levels reached 36% of a normal control.

Two of the three patients, however, experienced elevated liver enzyme counts and one case was classified as a serious adverse event. Enzyme levels returned to normal in both patients after supplemental oral steroids were given, leading Sarepta to modify the study protocol moving forward to include longer steroid treatment post-infusion.

Sarepta CEO Doug Ingram noted on a Wednesday conference call that such enzyme elevations have been observed in other gene therapy studies, claiming the issue is “very manageable” by using steroids.

While results show MYO-101’s promise, the data are preliminary and center on protein expression and other biomarker data. Ingram cautioned that it’s too early to draw any significant conclusions on whether those positive signals translate into a functional improvement.

Still, the CEO did signal confidence that the data supports the scientific rationale underpinning the four other limb-girdle muscular dystrophy programs in Myonexus’ pipeline. Each target a sub-type of the disease and three are in clinical stages.

Investors seemed to share that confidence, bidding up Sarepta’s stock price by as much as 10% in Wednesday morning trading.

By exercising its option, Sarepta now owns full rights to all five of Myonexus’ programs, strengthening the biotech’s pipeline.

The company will now move to take over the Investigational New Drug applications covering the three preclinical programs, as well as initiate a technology transfer from Nationwide Children’s to its manufacturing partner.

Sarepta also plans to hold a meeting with the Food and Drug Administration to discuss next steps for the five programs, including whether to dose higher to induce greater expression levels in an additional cohort.