Sarepta reveals positive results in limb-girdle gene therapy trial. What does that mean for DMD?
Sarepta on Monday unveiled a small batch of positive data for one of the gene therapies it bought out last year, sketching a path toward a pivotal study in 2021 and helping bolster the company’s broader gene therapy ambitions.
The gene therapy, known as SRP-9003, is designed to treat a rare degenerative disorder called limb-girdle muscular dystrophy by boosting production of a protein patients are missing, called beta-sarcoglycan. It was part of a basket of treatments Sarepta acquired in its $165 million-buyout of Myonexus last year. The biotech already showed a low dose of the therapy could lead to some increased expression of the missing protein and some improved muscle function in 3 kids, but it was unclear how long those results would last or if a higher dose would lead to better results.
On Monday, though, the company announced that their initial 3 patients had continued to improve. Although there was no control group, natural history studies suggested the average limb-girdle patient would decline by 4 points on a key measure of muscle function, called the North Star Assessment for Dysferlinopathy. Instead, the three kids improved by 5.6 points. They also improved on their ability to walk long distances and short distances and to stand up.
“All three subjects at every single time period have improved in every single one of their functional scores,” Sarepta gene therapy chief Louise Rodino-Klapac said on a conference call with investors. “All in all, very consistent results that are extending out one year.”
The company was hoping that giving a higher dose of the viral vector that delivers the missing gene would lead to greater production of the missing protein. Although there were no functional data for these 3 patients, they showed substantially greater protein production. The average percentage of muscle fibers was 72%, compared t0 51% in the first three. The mean intensity was 73% as opposed to 47%. And the overall amount of gene expression, as measured by a western blot, was 62%, as opposed to 36.1%.
Those numbers included one patient who scored a 97% on the mean intensity metric.
“At least one of the children in the high dose cohort has literally maxed the test out,” CEO Doug Ingram said on the call. “It’s hard to be more pleased than that.”
The data are still small and lacked a control group, and the therapy only works on a sliver of the larger limb-girdle population.
Still, analysts were pleased. The safety data — essentially no severe complications, save for one case of dehydration-induced vomiting — and the improvement across virtually every metric pointed not only to the potential of the particular treatment, but also of Sarepta’s other programs, including their Roche-partnered gene therapy for Duchenne muscular dystrophy.
“Today’s results show improvement in all biomarkers, relative to the low dose, with no new safety issues,” Baird’s Brian Skorney wrote in a note to investors. “Overall, this data continues to support our view that AAVrh74 [Sarepta’s vector] has a unique profile relative to competitors in the gene therapy space, and should reinforce both the DMD and LGMD opportunities.”
Although Sarepta has been an RNA-focused company for the vast majority of its 40-year history, most recently getting two muscular dystrophy drugs approved off that technology, it’s increasingly invested its future in gene therapy. Most prominently, they developed a Duchenne program that Roche paid $1.15 billion upfront to partner on last year. The Myonexus deal, although far smaller in size, brought five different gene therapies for five different forms of limb-girdle muscular dystrophy. If all are approved, Ingram said, that would account for 70% of limb-girdle patients.
All the company’s gene therapies use the same vector — a proprietary form of adeno-associated virus — allowing analysts to project the results from this study onto its other ones, including SRP-9001, the much-anticipated Duchenne trial due to read out next year.
“We believe the data further validates Sarepta’s gene therapy platform,” Mizuho’s Difei Yang wrote in a note to investors, “and provides an important, positive read-through to 1) SRP-9001 (microdystrophin gene therapy) given the similar vector, promoter, and dose (2e14), and 2) Sarepta’s pipeline of five additional LGMD indications.”
Ingram said the company will talk to regulators about setting up a pivotal trial for next year. The company wouldn’t commit to any details, although they implied that after today, some of those details should be obvious.
“The final dose for the registration trial will be selected in Q3,” Rodino-Klapac said, “but based on the safety and selection data we just showed you, I think it’s clear we’ll continue on the high dose.”