DMD Trial of Sarepta Therapeutics’ Exon-skipping Drug Encouraging

A recent article published in the Annals of Neurology describes promising results from a Phase 2b study of eteplirsen in patients with Duchenne muscular dystrophy (DMD). The study, titled “Longitudinal effect of eteplirsen vs. historical control on ambulation in DMD,” is the result of a collaborative effort between researchers from the U.S., Belgium and Italy.

DMD is a genetic condition in which muscles break down and become weak. It is caused by a lack of the protein dystrophin, which is crucial for maintaining healthy muscle cells. Right now, the most promising DMD medications intend to restore lost dystrophin.

Eteplirsen is a molecule developed by Sarepta Therapeutics, a biotechnology company focusing on RNA-based therapeutics. Eteplirsen is designed to restore messenger RNA (mRNA), creating a functional form of the dystrophin protein by using a genetic strategy known as “exon-skipping.”

The study used data from the Italian Telethon Network and the Leuven Neuromuscular Reference Group to analyze walking performance at baseline and 1,2 and 3 years. The researchers compared participants, boys aged 7 -13, who took eteplirsen to a historical control group of boys with typical DMD degeneration. At the three-year mark, boys taking eteplirsen walked an additional 151 meters in the six-minute walk test compared to the control group. Those taking eteplirsen also had a lower loss of ambulation (16.7%) compared to controls (46.2%).

Jerry Mendell, MD, Director of the Center for Gene Therapy and Muscular Dystrophy at Nationwide Children’s Hospital, in Columbus, Ohio, and the study’s first author, said in a press release: “As a clinician with extensive experience treating patients with Duchenne muscular dystrophy, it is apparent based on these data, that the boys treated with eteplirsen in this study are showing more signs of stability than would normally be expected at this stage of the disease. Remaining ambulatory is critical to greater independence over a longer period of time and a 151 meter difference indicates a marked slowing of disease progression. The safety and tolerability demonstrated by eteplirsen is also important, as exon skipping therapies will require lifelong dosing to be effective. For over three years, it continues to be one of the safest drugs I have used in my career.”

“Over the last 10 years, there has been an effort to harmonize standards of care, which has resulted in published guidelines that have allowed our center to generate and publish more reliable natural history data for Duchenne muscular dystrophy,” stated Eugenio Mercuri, Professor of Pediatric Neurology, Università Cattolica del Sacro Cuore, Rome, Italy. “The observations of the eteplirsen-treated boys in comparison to this matched natural history group shows an encouraging difference from what one would normally expect from the natural history of the disease.”

Hopefully, the medication will advance to Phase 3 studies based on these results — the final stage necessary before drug approval.