The FDA recently expanded its approval for a gene therapy to treat Duchenne muscular dystrophy (DMD), known as Elevidys (delandistrogene moxeparvovec-rokl). This decision was made despite the fact that the therapy failed a Phase III clinical trial last year. The approval came over the objections of three expert review teams and two directors at the FDA. Dr. Peter Marks, Director of the FDA’s Center for Biologics Evaluation and Research, played a significant role in the decision-making process.
Elevidys was initially approved last year through an accelerated approval process for use in DMD patients aged 4 and 5 who can walk. The recent decision expands access to the therapy for DMD patients of all ages, regardless of ambulatory status. While the FDA believes this approval will address the urgent treatment needs of patients with DMD, it has sparked criticism from those concerned about the agency’s decision-making process.
Critics have raised concerns about the FDA’s shift towards emotional rhetoric and patient advocacy over scientific evidence. They worry that decisions like this could undermine the credibility of the agency and erode trust in scientific institutions. The approval of Elevidys has highlighted internal conflicts within the FDA, as review documents and memos show a stark divide between agency staff and Dr. Marks.
FDA statisticians and clinical teams have expressed doubts about the effectiveness of Elevidys for the expanded indication. They argue that the clinical trial results do not provide substantial evidence to support the therapy’s approval for all DMD patients. Despite these concerns, Dr. Marks found the secondary endpoints of the trial compelling enough to warrant approval.
In response to the dissenting opinions, Dr. Marks defended his decision by stating that the secondary and exploratory endpoints, along with additional data, met the standard for substantial evidence of effectiveness. However, if he had not overruled the agency’s reviewers and directors, a recommendation would have been made for an additional study of Elevidys in specific patient subgroups. The approval of Elevidys has raised questions about the FDA’s approval process and the influence of top officials on decision-making.
The controversy surrounding the approval of Elevidys highlights the challenges faced by regulatory agencies in evaluating novel therapies for rare diseases. It underscores the importance of transparent decision-making processes and the need to balance patient advocacy with scientific evidence. Moving forward, it will be crucial for the FDA to address concerns raised by critics and ensure that future approvals are based on rigorous scientific evaluation.
