There were no serious adverse events reported and no patients discontinued from the study.
Sarepta Therapeutics’ delandistrogene moxeparvovec (SRP-9001), an investigational gene therapy intended to treat ambulant individuals with Duchenne muscular dystrophy (DMD), has demonstrated functional improvements and safety in 4-year data from 4 patients treated in a phase 1/2a clinical trial (SRP-9001-101; NCT03375164).1 The data were presented orally in a session entitled “Gene and Cell Therapy Trials in Progress” at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California.
In terms of functional outcomes, the patients, who had a mean age of 5.1 years at baseline, showed a mean improvement in North Star Ambulatory Assessment (NSAA) total scores of 7.0 (SD, 2.9) from baseline to 4 years posttreatment. This improvement stands in contrast to the decline typically expected in this age range for patients with DMD. Improvements were also observed from baseline to 4 years posttreatment in the patients’ mean scores for other functional tests including Mean Time to Rise, Mean 4-stair Climb, Mean 100 Meter Walk/Run (MWR), and Mean 10MWR.
Eleonora D’Ambrosio, MD, a gene therapy fellow at Nationwide Children’s Hospital, Columbus Ohio, who presented the data on behalf of the study authors, pointed out that a particularly notable improvement of 60% was observed on the Mean 4-stair Climb test. The results from the clinical trial were also compared to an age-matched, propensity-score-weighted external control (EC) comparator group (n = 21). It was found that the difference in change from baseline NSAA total score to 4 years posttreatment between the trial group and the EC group was 9.9 (descriptive mean) or 9.4 (least square median; SE, 3.4), favoring the trial group.
In terms of safety, there were no serious adverse events (AEs) reported and no patients discontinued from the study. Treatment-related (TR) AEs occurred mostly within the first 70 days of treatment. All TRAEs were mild to moderate in severity and all resolved on their own. The most common TRAE was vomiting, which made up half of the 18 TRAEs. D’Ambrosio noted that this TRAE generally occurred in the first week following treatment and that it did not correlate with any abnormalities, including liver enzyme elevations.
“And speaking of liver enzymes, gamma-glutamyl transferase was actually elevated in 3 out of 4 patients in the first 3 months posttreatment and also resolved with increasing the steroid dose,” D’Ambrosio said.1 “These changes were asymptomatic."
"There were no hospitalizations and none of the AEs was associated with complement activation—so there was no cell lysis, no inflammation, no opsonization or thrombotic microangiopathies—and no other significant laboratory findings,” D’Ambrosio added.
The ages of the 4 patients treated in the study ranged from 4.0 to 6.0 at baseline and their baseline NSAA scores ranged from 18.0 to 26.0. One patient (referred to as Patient 1) had a height of 109.9 cm, a weight of 18.4 kg, and a BMI of 15.2 at baseline. Meanwhile, Patient 2 was 104.3 cm, 18.9 kg, and had a 17.4 BMI; Patient 3 was 110.0 cm, 21.4 kg, and had a 17.7 BMI; Patient 4 was 95.7 cm, 13.7 kg, and had a BMI of 15.0.
“I just want to highlight their BMI, [which ranged from approximately] 15-17, which is lower compared to what we would expect in this population at this age,” D’Ambrosio said.1 “It has been observed [in other studies] that patients with lower BMI actually respond better to gene transfer.”
D’Ambrosio concluded by stating that the study’s results suggest durable expression of SRP-9001 and provide supporting evidence that a single administration of SRP-9001 is well-tolerated. A biologics license application (BLA) for SRP-9001 is currently under review by the FDA.2 On May 24, 2023, Sarepta Therapeutics announced that the agency pushed the PDUFA date for the BLA from May 29, 2023, to June 22, 2023, citing a need for final label negotiations and postmarketing commitment discussions.