Understanding the Disconnect Between Trials of Duchenne Therapies and Real-World Data: Dongzhe Hong, PhD


The postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School provided answers to a recently published study highlighting the burden of care and infrequent use of novel exon-skipping drugs for Duchenne in clinical settings. [WATCH TIME: 3 minutes]

WATCH TIME: 3 minutes

"This selective enrollment [in clinical trials] can lead to over-estimation of the drug’s effectiveness in a broader and more diverse population seen in the real-world. There might be inherent limitations in the medication themselves, when applied to patients at different stages of DMD or with varying comorbidities, which are not fully captured in the controlled environment of clinical trials."

Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness because of alterations in the dystrophin protein that helps keep muscle cells intact. Exon-skipping therapies, considered disease-modifying, were introduced in 2016 with the approval of eteplirsen (Exondys 51; Sarepta Therapeutics), an antisense oligonucleotide designed to increase dystrophin production.

Eteplirsen’s approval was met with controversy related to the pivotal trial, which enrolled 12 patients and demonstrated miniscule increases in the surrogate measure end point of dystrophin levels, suggesting it may not have any real clinical benefit. The drug is also expensive for patients, costing approximately $300,000 per year for patients with typical weight and reaching as high as approximately $1 million per year for a patient weighting 40 kg. Following eteplirsen’s approval, other agents, including golodirsen, viltolarsen, and casimersen, were approved based on similarly limited evidence.

A recently published study in JAMA Network Open examined the differences in demographic and disease characteristics of patients receiving novel DMD drugs in clinical trials compared with routine care settings. Comprised of 223 routine care patients and 106 patients in pivotal trials, results showed that those prescribed DMD treatments during routine care were in later stages of disease and older than those I clinical trials. In addition, routine care patients discontinued treatment after approximately 7 months, and payers incurred substantial expenses for these medications.

Following the publication, NeurologyLive® sat down with lead author Dongzhe Hong, PhD, to understand the reasons as to why exon-skipping therapies have not translated to the real-world. Hong, a postdoctoral research fellow at Brigham and Women’s Hospital and Harvard Medical School, discussed the selective enrollment criteria used for these trials and whether exon-skipping therapies are truly being effectively implemented in clinical care. Furthermore, he commented on the prescribing process of these novel agents, complications with insurance, and the negative effects of receiving medications in later stages of the disease.

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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