Sarepta Therapeutics announced topline results from Part 1 of Study SRP-9001-102 for its gene therapy SRP-9001 for Duchenne muscular dystrophy.
Photo courtesy of Sarepta.
Sarepta Therapeutics announced topline results from Part 1 of Study SRP-9001-102 for its gene therapy SRP-9001 for Duchenne muscular dystrophy (DMD). The study hit the mark on its primary biological endpoint of micro-dystrophin protein expression. However, on the primary functional endpoint, meaning how well the patients actually responded, there was an increase in NSAA total score compared to placebo at 48 weeks, but it was not statistically significant. NSAA is a 17-point rating scale that measures functional motor abilities in ambulant children with DMD.
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DMD is a muscle wasting disease caused by mutations in the dystrophin gene. It is a progressive disease that usually causes death in early adulthood, with serious complications that include heart or respiratory-related problems. It mostly affects boys, about 1 in every 3,500 or 5,000 male children.
SRP-9001 is an investigational gene transfer therapy. The goal is to deliver the micro-dystrophin-encoding gene to the muscle tissue for what the company refers to as targeted production of the micro-dystrophin protein. The lack of dystrophin, a muscle protein, is the cause of the disease. There are a few therapies approved now for DMD, notably Sarepta’s Exondys 51. But Exondys 51 requires regular dosing. The goal of SRP-9001 is to be a “one-and-done” gene therapy. However, the reason all the therapies use either truncated genes or gene-skipping technology is the dystrophin gene is the largest in the human body and is too big to fit into viral vectors typically used in gene therapies.
The study data did reinforce the safety and tolerability profile—there were no new safety signals observed. About 85% of the patients in the treatment group had at least one treatment-related adverse event compared to 43% in the placebo group, but no clinical activation of the complement system was seen, which is an immune response. Of the adverse events, 82% were mild or moderate, and four participants reported serious treatment-related adverse events, although one of those people was in the placebo group.
“Study 102 reinforces our confidence in the potentially transformative benefits of SRP-9001, including among other things, the fact that in the Study’s pre-specified analysis, the participants in the 4-5 age group robustly achieved a statistically significant and clinically meaningful improvement in NSAA over placebo, as predicted by our prior Study 101,” said Doug Ingram, president and chief executive officer of Sarepta.
He went on to say, “For the entire population, while we saw separation at every time point between the active and placebo cohorts, Study 102 did not achieve statistical significance on the primary functional endpoint. In this regard, we are very disappointed that the randomization process resulted in a significant imbalance in baseline NSAA scores between the active and placebo cohorts of the participants ages 6-7, making the 6-7 age groups non-comparable and likely substantially contributing to the inability to achieve statistical significance.”
The study remains blinded and the company will analyze the functional patient data, including cross-over participants, once they have hit the 48-week mark in Part 2 of the study. Currently they have enrolled and dosed 11 patients in Study 103 and expect biomarker and safety data in the second quarter.
Meanwhile, Pfizer also announced yesterday that they had dosed the first patient in the Phase III CIFFREO trial for their gene therapy for DMD. The trial expects to enroll 9 ambulatory boys, ages 4 through 7, at 55 clinical sites in 15 countries.
