Sarepta’s DMD Gene Therapy Elevidys Shows Sustained Benefit in Updated Phase 3 Data
With regard to safety, the company stated that no new safety signals have been reported.
Sarepta Therapeutics’ delandistrogene moxeparvovec-rokl (marketed as Elevidys), a marketed adeno-associated virus (AAV) vector-based gene therapy for patients with Duchenne muscular dystrophy (DMD), has shown sustained benefit in patients who are ambulatory who were treated in the phase 3 EMBARK clinical trial (NCT05096221; SRP-9001-301), according to new results from part 2 of the study.1
Among 59 patients in part 2 who crossed over to receive treatment with Elevidys after having received the placebo in part 1 of the study, a least square means (LSM) improvement of +2.34 points from baseline on the North Star Ambulatory Assessment (NSAA) in comparison to a matched external controlgroup (EC) at 52 weeks posttreatment (P < .0001). In addition, the patients treated with Elevidys in part 2 also showed an LSM –2.70 seconds improvement on Time to Rise (TTR) (P < .0001) and an LSM –1.07 seconds improvement on 10-meter walk/run (10MWR) (P = .0001) in comparison to a prespecified, propensity-weighted EC. Sarepta noted that the study remained blinded during the 52 weeks posttreatment period in part 2 and that the cross-over treated patients had an average age of 7.18 years, whereas the patients treated in part 1 of the study had had an average age of 5.98 years.
Sarepta also reported updated 2 year results from the 63 patients who originally received Elevidys in part 1 of EMBARK. At 2 years posttreatment, the patients treated with the gene therapy in EMBARK showed an LSM improvement of +2.88 points on NSAA (P =. 0001), -2.06 seconds on TTR (P = .0033), and –1.36 seconds on 10MWR (P =.0028) in comparison to EC. The company pointed out that an increased difference from 1 year posttreatment to 2 years posttreatment on NSAA, TTR, and 10MWR was observed between patients treated with Elevidys in part 1 and the EC, suggesting a continued widening of the chasm in disease trajectory between patients who received the gene therapy and the natural history course of the disease.
Sarepta also noted that consistent and sustained expression of the microdystrophin encoded by Elevidys was observed in biopsies taken from patients treated in part 1 at 12 weeks posttreatment and 64 weeks posttreatment. With regard to safety, the company stated that no new safety signals have been reported.
“We’re very encouraged to see the results from part 2 of EMBARK as they further elucidate the impact Elevidys has on disease progression in a blinded, controlled study,” Louise Rodino-Klapac, PhD, the executive vice president, head of R&D, and chief scientific officer of Sarapeta, said in a statement.1 “Skeletal muscle MRI demonstrates the importance of preserving muscle, and the functional outcome results show disease stabilization sustained through 2 years after treatment. Over time, we continue to observe a statistically significant difference favoring Elevidys compared to a well-matched external control on NSAA and timed tests. The consistency and totality of evidence supporting a long-term and clinically meaningful treatment benefit with Elevidys continues to grow. We look forward to sharing more details with the clinical community in upcoming scientific forums.”
The FDA originally approved Elevidys in June 2023 for ambulatory patients aged 4 through 5 years with DMD and a confirmed mutation in the DMD gene, excluding patients with any deletion in exon 8 and/or exon 9.2 The agency expanded its indication in June 2024 to include ambulatory patients (via traditional approval) and nonambulatory patients (via accelerated approval) with a confirmed mutation in the DMD gene who are 4 years of age or older and who do not have any deletion in exon 8 or exon 9 in the gene.3
In September 2024, CGTLive® spoke to John Brandsema, MD, a pediatric neurologist in the Division of Neurology at Children’s Hospital of Philadelphia, to get his view on the newly emerging landscape of care for DMD and experience that had been gained with Elevidys at the time. He emphasized the need for more long-term data, especially for older patients, as many patients treated thus far have been on the younger end of the spectrum.
“While the label is broad and is for everyone we don't necessarily have the data to back that up yet and that makes the conversation more nuanced,” Brandsema told CGTLive. “We also aren't sure about the durability of transgene expression. Muscle is a high turnover tissue, and therefore whether this is going to be a lifelong effect is still up in the air; although it does seem, from the early boys treated that there is a measurable difference in their trajectory years after the dose, up to 5 or 6 years at this point now.”
