Pfizer pauses DMD trial segment after patient death

This week, Pfizer announced the unexpected death of a participant in its phase 2 DAYLIGHT study, which is evaluating a new gene therapy for Duchenne muscular dystrophy (DMD) in pediatric patients. This trial involves the administration of fordadistrogene movaparvovec, a gene therapy aimed at addressing the genetic cause of DMD.

The participant received the gene therapy treatment, first administered in early 2023. Following this tragic event, Pfizer decided to halt dosing in the crossover portion of its subsequent phase 3 CIFFREO trial. This trial targets a slightly older demographic, specifically boys aged 4 to under 8 years. The CIFFREO trial had completed its initial dosing phase in the prior year and employs a placebo-controlled, randomized crossover design.

Despite this pause, Pfizer assured that other activities within the CIFFREO trial will continue as planned. The suspension of dosing does not impact other ongoing trials within the fordadistrogene movaparvovec program, as dosing for those studies has already been completed.

Earlier, the trial had faced a similar suspension in December 2021, following the death of a patient in the non-ambulatory cohort of the phase 1b study. Pfizer later attributed that death to advanced disease and underlying cardiac dysfunction. Subsequently, the company amended the trial protocol to include a seven-day hospital stay for close monitoring after dosing. This amendment allowed the study to resume in March 2022.

Fordadistrogene movaparvovec operates by using a modified virus to deliver a functional version of the dystrophin gene directly into muscle cells. This gene encodes a shortened version of the dystrophin protein, known as micro-dystrophin, which aids in improving muscle function and slowing the progression of DMD. The therapy aims to offer a long-term treatment solution by compensating for the defective gene responsible for the disorder.

This gene therapy represents a significant advancement in the treatment of DMD, a debilitating condition that primarily affects boys and gradually leads to muscle degeneration and weakness. Current treatments for DMD are limited, and the development of gene therapies like fordadistrogene movaparvovec holds promise for providing more effective and long-lasting solutions.

The recent death underscores the challenges and risks associated with developing new treatments for complex genetic disorders. While the suspension of dosing in the CIFFREO trial is a setback, it highlights the importance of patient safety and the need for rigorous monitoring in clinical trials.

Pfizer remains committed to advancing its fordadistrogene movaparvovec program and continues to explore the potential of gene therapy for DMD. The company is working closely with regulatory authorities to determine the next steps and ensure the safety of all participants in its trials.

In summary, the sudden death of a participant in Pfizer's phase 2 DAYLIGHT study has prompted the company to pause dosing in its phase 3 CIFFREO trial. Despite this, other aspects of the trial will proceed, and ongoing trials in the gene therapy program are unaffected. The incident highlights the complexities and risks of developing new treatments for genetic disorders but underscores Pfizer's commitment to patient safety and the potential of gene therapy to transform the treatment landscape for DMD.