Reassessing the Process of Drug Development for Duchenne Muscular Dystrophy: Dongzhe Hong, PhD


The postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School discussed some of the issues with ensuring timely care access to approved therapies for patients with Duchenne muscular dystrophy. [WATCH TIME: 3 minutes]

WATCH TIME: 3 minutes

"One possibility is that prescribing physicians aren’t aware of the age range that received the drug in its pivotal trials or have knowledge on the FDA-approval process. When patients receive the drug at a later stage of their DMD, it might impact the predicted effectiveness of the medications."

For years, Duchenne muscular dystrophy (DMD) was mainly treated with a combination of corticosteroids, assistive devices, and cardiac and respiratory support until 2016, when the exon-skipping therapies began to emerge. The first approved therapy was eteplirsen (Exondys 51; Sarepta Therapeutics), an antisense oligonucleotide designed to increase dystrophin, followed by other agents, which include golodirsen, viltolarsen, and casimersen. Immediately following eteplirsen’s approval, the manufacturer set a price of approximately $300,000 per year for patients with typical weight.

Years after the introduction of these therapies, a cross-sectional study evaluated the differences in demographic and disease characteristics of patients receiving novel DMD drugs in clinical trials vs those in routine care settings. Led by Dongzhe Hong, PhD, the study revealed that while nearly all patients in the pivotal trials had DMD disease stage 1 or 2 when initiating treatments (97.2%; n = 103), in the postapproval clinical setting, slightly more than one-third of patients were in disease stage 3 or 4. In addition, approximately one-third of routine care patients discontinued the treatments after approximately 7 months.

These data, published in JAMA Network Open, raise concerns about the translation of DMD drug trial findings to routine care settings. Hong, a postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical, sat down with NeurologyLive® to discuss the flaws in DMD drug development and where the clinical community can continue to improve. In addition, he spoke on the challenging position regulators face when assessing drugs with small risk benefits in disorders that are desperate for improved treatment options.

1. Hong D, Avorn J, Wyss R, Kesselheim AS. Characteristics of patients receiving novel muscular dystrophy drugs in trials vs routine care. JAMA Netw Open. 2024;7(1):e2353094. doi:10.1001/jamanetworkopen.2023.53094
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