Sarepta and Roche Report DMD Gene Therapy Demonstrates Functional

Sarepta and its partner Roche presented new results and analyses on their experimental gene therapy SRP-9001 for the neuromuscular condition Duchenne muscular dystrophy showed consistent, statistically significant functional benefits in individuals.

Photo: Doug Ingram, president and CEO of Sarepta

Duchenne muscular dystrophy (DMD) is a rare, fatal neuromuscular genetic disease that occurs in approximately one in every 3,500-5,000 newborn males worldwide. DMD is caused by a change or mutation in the gene that encodes instructions for dystrophin. Symptoms of DMD usually appear in infants and toddlers. Affected children may experience developmental delays such as difficulty in walking, climbing stairs or standing from a sitting position. As the disease progresses, muscle weakness in the lower limbs spreads to the arms and other areas. Most patients require full-time use of a wheelchair in their early teens, and then progressively lose the ability to independently perform activities of daily living such as using the restroom, bathing, and feeding. Eventually, increasing difficulty in breathing due to respiratory muscle dysfunction requires ventilation support, and cardiac dysfunction can lead to heart failure. The condition is universally fatal, and patients usually succumb to the disease in their twenties.

SRP-9001 (delandistrogene moxeparvovec) is an experimental gene transfer therapy intended to deliver SRP-9001 to muscle tissue for the targeted production of essential components of dystrophin. Sarepta is responsible for global development and manufacturing for SRP-9001 and plans to commercialize SRP-9001 in the United States upon receiving FDA approval. In December 2019, Roche partnered with Sarepta to combine Roche’s global reach, commercial presence, and regulatory expertise with Sarepta’s gene therapy candidate for Duchenne to accelerate access to SRP-9001 for patients outside the United States.

In the 20-patient Cohort 1 of SRP-9001-103 (ENDEAVOR), SRP-9001-treated participants improved 4 points from their pre-therapy baselines, and 3.8 points (unadjusted means) and 3.2 points (least squared means) at 52 weeks on the North Star Ambulatory Assessment (NSAA) compared to a propensity-weighted external control group. The companies said the results from ENDEAVOR reinforces confidence in our ongoing phase 3 Study SRP-9001-301.

Additionally, across multiple new analyses, discussed below, SRP-9001 treated patients showed statistically significant and clinically meaningful benefit versus propensity-matched external controls and results positively diverge from the natural history of this degenerative disease over time.

In the 4-patient Study SRP-9001-101, at 4 years, patients – currently on average over 9 years old and in the predicted steep decline phase of disease – did not decline but showed a 7-point increase above their pre-treatment baselines on NSAA, and 9.9 point (unadjusted means) and a 9.4 point (least squared means) improvement versus a propensity-weighted external control.

In a 52-patient integrated analysis across Studies 101, 102, and 103 at target dose, at one year, SRP-9001 treated patients improved 3.1 points (unadjusted means) and 2.4 points (least squared means) on NSAA versus propensity-weighted external control.

While the safety and tolerability profile of SRP-9001 is similar to past reports with the most common treatment-related adverse event being vomiting there was one new serious adverse event of myocarditis in Study 9001-103, Cohort 2 (older ambulatory patients >8 years old). The patient had no signs or symptoms of systolic dysfunction and received IV methyl-prednisolone and additional chronic cardiac medications added post-event. Cardiac MRI at one month showed normal function and partial resolution of myocarditic changes, and ECHO at four months showed normal systolic function.

“We now have positive results across multiple studies and multiple time points, including one-, two- and four-years after treatment, and are very pleased with the consistent safety profile across more than 80 treated patients,” said Doug Ingram, president and CEO of Sarepta. “We are particularly excited about the results of cohort 1 of Study 103, as these results come from our commercially representative process at our intended commercial dose.

Author: Rare Daily Staff