#apaperaday: Boy Dosed with Pfizer’s Duchenne Muscular Dystrophy Gene Therapy Dies a Year After Phase II Trial

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Boy Dosed with Pfizer’s Duchenne Muscular Dystrophy Gene Therapy Dies a Year After Phase II Trial

A sad short paper (or rather an update) by Philippidis in Human Gene Therapy on the boy with Duchenne who died in the Pfizer microdystrophin gene therapy trial DAYLIGHT. DOI: 10.1089/hum.2024.53426.bfs

Pfizer’s gene therapy for Duchenne is called fordadistrogene movaparvovec and it is a micro-dystrophin delivered by AAV9. It is tested in a phase 3 clinical trial (where the 1 year results did not show efficacy recently – though likely because the trial was too short).

However, in parallel there was also a trial in very young patients aged 2-4 years. In this trial one of the treated boys died this year after being treated last year. We do not know any more details, but as the patient was treated last year, it was not an acute effect.

The author outlines the consequences of this sad death: dosing is stopped for the DAYLIGHT trial, but also dosing is stopped for the patients in the phase 3 CIFERO trial where placebo treated patients would receive the gene therapy after a year.

This is a disappointment for those in the trial, but of course until we know what happened safety comes first. The author outlines that all treated patients will be followed up for at least 5 years for potential safety issues.

This sad death does bring home that gene therapy is still a pioneering approach where we do not know what we do not know and where unexpected things keep happening, even though hundreds of patients now have been treated.

Without more details it is impossible to figure out what has caused this death. Is it micro-dystrophin related? AAV related? AAV9 related? Not related to gene therapy at all? Hopefully more information will be forthcoming so we can learn as a field.