The Regulatory Repercussions of Approving Muscular Dystrophy Medications on the Basis of Limited Evidence.

The U.S. Food and Drug Administration (FDA) approved eteplirsen (Exondys 51) for Duchenne muscular dystrophy in 2016 via its accelerated approval program on the basis of a study of 12 boys. After a contentious review process and a high-profile meeting of an external advisory committee, FDA leaders concluded that very small increases in treated patients' levels of dystrophin, a muscle protein, were reasonably likely to predict clinical benefit. The eteplirsen approval, which was followed by approvals of other drugs in the same class via the same pathway, has been controversial because of the questionable evidence underlying these decisions, delays in mandated postapproval testing, and high U.S. prices. Questions remain about the effectiveness and long-term safety of these products. Although the FDA initially set a November 2020 deadline for eteplirsen's manufacturer to complete a clinical trial determining whether the drug has clinical benefit, the company will not complete the trial until 2024 or later. The relationship between levels of truncated dystrophin, the muscle protein studied in eteplirsen's pivotal trial, and clinical outcomes remains uncertain. Despite recent legislative and regulatory changes to the FDA's accelerated approval pathway, the history of eteplirsen and similar drugs points to the need for additional reforms to better balance evidence generation with patient safety and access to promising medications. Lawmakers and regulators should take further action to limit excessive spending on unproven therapies and ensure that drug sponsors conduct robust and timely confirmatory trials after receiving accelerated approval.