ICER opposes FDA's potential full approval of Sarepta's gene therapy

The integrity of the FDA’s accelerated approval process could be questioned if the agency grants full approval to treatments that have failed their mandatory confirmatory trials. This concern was raised by David Rind, the Chief Medical Officer at the Institute for Clinical and Economic Review (ICER), in a recent paper published in the Journal of the American Medical Association.

In his publication, Rind scrutinizes the FDA’s accelerated approval of Sarepta Therapeutics’ Elevidys, a gene therapy designed to treat Duchenne muscular dystrophy. He criticizes the surrogate endpoint the FDA used for its approval and raises concerns about the possibility of the treatment receiving full approval in the coming month. This gene therapy costs a substantial $3.2 million, an amount Rind argues is difficult to justify, especially when compared to other high-cost treatments that have demonstrated curative benefits.

Rind's critical examination brings attention to the broader implications of the FDA's accelerated approval process. This pathway is designed to expedite the availability of drugs for severe conditions that lack effective treatments by allowing approval based on surrogate endpoints. These are typically biomarkers thought to predict clinical benefit but are not direct measures of it. While this approach can hasten the delivery of promising therapies to patients in desperate need, it also carries the risk of approving treatments that may not ultimately demonstrate meaningful clinical outcomes in confirmatory trials.

The case of Elevidys is particularly emblematic of this broader issue. Duchenne muscular dystrophy is a severe, progressive condition that leads to muscle degeneration and weakness. Finding an effective treatment is of utmost importance to patients and their families. The FDA's decision to grant accelerated approval to Elevidys was based on a surrogate endpoint involving a biomarker related to dystrophin, a protein lacking in patients with Duchenne muscular dystrophy. However, the reliance on this biomarker instead of direct clinical outcomes has sparked debate.

Rind’s article underscores the need for rigorous evaluation of the therapeutic benefits relative to their costs. He highlights that the $3.2 million price tag for Elevidys is particularly concerning given the lack of confirmatory evidence demonstrating its effectiveness. He contrasts this with other high-priced treatments that have undergone rigorous testing and have shown clear curative benefits, implying that Elevidys may not represent a justified investment.

The broader implications of Rind’s critique suggest the need for a reassessment of how surrogate endpoints are utilized in the accelerated approval process. If the FDA continues to grant full approval to drugs that fail to meet their confirmatory trial endpoints, it could undermine public trust in the regulatory framework designed to ensure the safety and efficacy of new treatments.

In conclusion, the FDA’s accelerated approval pathway is a double-edged sword. While it has the potential to bring groundbreaking therapies to market more swiftly, it also raises significant questions about the adequacy of surrogate endpoints and the justification of high treatment costs in the absence of robust clinical evidence. David Rind’s scrutiny of the Elevidys approval serves as a timely reminder of the need for a balanced approach that safeguards the integrity of the approval process and ensures that patients have access to truly effective and fairly priced treatments.