RARE Daily

Researchers Take Aim at DMD Therapies to Make Case for Timely Completion of Confirmatory Trials

March 13, 2024

Rare Daily Staff

Spending on targeted DMD therapies reached $3.7 billion from 2016 to 2022, despite limited evidence of efficacy, according to a Research Letter published in JAMA.

The authors from the Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital in Boston note that since 2016, the U.S. Food and Drug Administration has granted accelerated approval to five genetically targeted therapies for Duchenne muscular dystrophy.

The analysis comes as there is growing controversy over the use of accelerated approval and the failure of drug developers to complete confirmatory studies as required in a timely manner. The authors said more than half of the drugs granted accelerated approval from 2012 to 2021 did not complete confirmatory trials by the FDA’s deadline.

Duchenne muscular dystrophy (DMD) is a severe, progressive, degenerative muscle disease. It is caused by mutations in the Duchenne gene which encodes for dystrophin, a protein involved in muscle cell structure and signaling pathways. Without dystrophin, muscles throughout the body degenerate and become weak, eventually leading to loss of movement and independence, required support for breathing, cardiomyopathy and premature death.

The authors said that the approvals for the drugs in their analysis were based on studies that showed a small mean increase in patients’ muscle dystrophin levels, which the agency found reasonably predicted a clinical benefit. But confirmatory studies from three of the drugs eteplirsen, golodirsen, and casimersen have not been completed.

The DMD gene therapy, delandistrogene moxeparvovecrokl, failed to meet its primary endpoint compared with placebo. A trial of viltolarsen has been completed but results have yet to be made public. Both of those drugs were not included in the numbers because of the approval date or the lack of available data on spending.

Despite limited evidence of efficacy, these DMD products are expensive. Eteplirsen can cost more than $1 million per year and delandistrogene moxeparvovecrokl costs $3.2 million for a one-time treatment.

They estimated that Medicare and Medicaid spending on these drugs during the period totaled an inflation-adjusted $1.2 billion.

“This analysis of Duchenne muscular dystrophy–targeted therapies sheds light on controversies relating to drugs’ limited preapproval evidence of efficacy, high prices, and delayed confirmatory trials,” the authors wrote. “As the FDA considers approving multimillion-dollar therapies with novel mechanisms of action and scant preapproval evidence of clinical benefit, policymakers should encourage timely completion of confirmatory trials and minimize financial risk in case treatments prove ineffective. Limiting Medicare and Medicaid reimbursement for accelerated approval drugs and alternative payment contracts for cell and gene therapies should be considered.”


Stay Connected

Sign up for updates straight to your inbox.