NEW YORK – Sarepta Therapeutics still intends to expand the approved indication for its gene therapy Elevidys (delandistrogene moxeparvovec) to all Duchenne muscular dystrophy (DMD) patients, despite not meeting the primary endpoint in the Phase III EMBARK trial, the company said on Monday.
Elevidys, an adeno-associated virus vector-based gene therapy, delivers a gene that encodes for microdystrophin, a protein engineered by Sarepta to carry out the normal functions of dystrophin. Patients with certain DMD gene mutations lack the dystrophin protein.
In June, the US Food and Drug Administration granted accelerated approval to Elevidys as a treatment for DMD patients between 4 and 5 years old based on data from a Phase II trial that showed the therapy increased microdystrophin expression after 12 weeks. Sarepta had not demonstrated a clinical benefit for Elevidys, although the FDA deemed the surrogate endpoint of microdystrophin expression "reasonably likely" to predict efficacy. The company had initially sought accelerated approval for Elevidys as a treatment for DMD patients of all ages but the agency limited the gene therapy's indication to children between 4 and 5 years old after seeing data submitted by the firm.
In the double-blind, placebo-controlled EMBARK study, Sarepta aims to confirm that Elevidys improves DMD patients' physical function and mobility. Although boys in the study with DMD aged 4 to 7 who received Elevidys improved 2.6 points on the North Star Ambulatory Assessment (NSAA) scale 52 weeks after treatment, compared to a 1.9-point improvement among placebo-treated patients, the 0.65-point difference fell short of reaching statistical significance. This was the primary endpoint in the study.
Nevertheless, Sarepta is choosing to highlight that the trial did meet statistical significance on all specified secondary endpoints, including showing that Elevidys positively impacted levels of microdystrophin expression as well as other mobility outcomes and upper extremity functions. Additionally, Sarepta said that no new safety signals were observed with Elevidys in this trial.
"The results of EMBARK support the conclusion that Elevidys modifies the trajectory of Duchenne and benefits patients across age groups living with this ferociously degenerative disease," Sarepta President and CEO Doug Ingram said in a statement. "Indeed, passing five seconds on time to rise is the strongest predictor of early loss of ambulation, and in EMBARK, Elevidys reduced those odds over 52 weeks by greater than 90 percent."
Based on this latest data readout, Cambridge, Massachusetts-based Sarepta remains focused on pursuing that label expansion for Elevidys in DMD patients of all ages.
"We have shared the EMBARK top-line results with FDA leadership and they have confirmed that, based on the totality of the evidence, they are open to such label expansion if supported by review of the data, and that they intend to proceed rapidly with consideration of the submission," Ingram added.
The company intends to share detailed results from EMBARK at future medical meetings and publish the data in a medical journal.