Pfizer pauses phase 3 gene therapy trial after young boy's fatal cardiac arrest

A young boy with Duchenne muscular dystrophy (DMD) who was participating in Pfizer's phase 2 gene therapy trial has tragically passed away. This incident was disclosed by Pfizer in a letter dated May 7 and referenced by the nonprofit organization Parent Project Muscular Dystrophy.

On May 3, the boy suffered cardiac arrest, which was classified as a fatal serious adverse event in the DAYLIGHT study, according to a Pfizer spokesperson in communication with Fierce Biotech on May 8. Pfizer has stated that they are collaborating with the trial investigator and an independent external data monitoring committee to gather information and analyze data to determine the cause.

The boy had received Pfizer's investigational gene therapy, fordadistrogene movaparvovec, in early 2023. This therapy is a recombinant adeno-associated virus gene treatment aimed at DMD. The DAYLIGHT study included boys aged 2 to 3 years old.

In addition to the phase 2 trial, Pfizer also completed initial dosing in 2023 for its phase 3 CIFFREO trial. This trial, which uses a crossover design, is investigating the same gene therapy in boys aged 4 to less than 8 years old. However, in light of the recent death, Pfizer has paused the dosing for the crossover portion of the CIFFREO trial. The company is also working with regulatory authorities to provide more information as it becomes available.

Despite the pause in CIFFREO dosing, other ongoing trials involving the gene therapy will continue as planned. Many of these studies have already completed their dosing phases. Pfizer emphasized that the safety and well-being of patients in their clinical trials remain a top priority. They are committed to transparently sharing more information with both the medical and patient communities as soon as they can.

Pfizer acknowledged that many within the patient community are hopeful about the potential benefits of fordadistrogene movaparvovec for treating DMD. The company will continue to collect and evaluate data from their trials to assess the therapy's effectiveness in addressing the disease. The DAYLIGHT study specifically aims to measure the safety and dystrophin expression of the gene therapy, with an anticipated primary completion date by the end of this year.

In October 2023, Pfizer’s Chief Scientific Officer and President of R&D Mikael Dolsten, M.D., Ph.D., described the investigational gene therapy as the "main game in town" during a quarterly earnings call. His comments followed the failure of a confirmatory trial for Sarepta Therapeutics’ DMD candidate, Elevidys, which did not meet the primary goal of its pivotal study.

Dolsten mentioned that Pfizer’s candidate, also known as PF-06939926, has demonstrated a consistent effect across various biomarkers and functional endpoints. However, this recent death is not the first associated with PF-06939926. In December 2021, another young male patient died in a phase 1 DMD trial, leading Pfizer to pause screening and dosing in that study, and the FDA subsequently placed a clinical hold on it.

Prior to these incidents, Pfizer had already identified safety concerns during a phase 3 trial testing ambulatory function. After three adverse events were reported, the company adjusted the study protocol to exclude patients with certain gene mutations.

DMD is a rare genetic disorder characterized by progressive muscle degeneration, primarily affecting boys and occurring in about one in every 5,000 live births.