Pfizer has recently paused its Phase III clinical trial that has been assessing the Duchenne muscular dystrophy candidate fordadistrogene movaparvovec. The Phase II DAYLIGHT trial (NCT05429372), enrolled ten boys ages two years to just under four years of age. A boy died recently after receiving treatment one year ago. His age has not yet been disclosed. The boy was one of the patients who the received the gene therapy fordadistrogene movaparvovec.
Pfizer literature emphasizes that the gene therapy is still in the clinical stage and has not been approved by the FDA. Dosing had been completed in the Phase II DAYLIGHT trial. It has also been completed in the Phase III trial CIFERO (NCT04281485) that enrolled older boys from age four to just under age 8. Pfizer said that while the company is reviewing data with regulators, the ‘crossover’ period for boys who had received placebo and were later scheduled to receive the investigational gene therapy, has also been put on hold.
About the Gene Therapy
The therapy is a recombinant process whereby segments of DNA are broken and recombined to produce new alternative forms of genes (alleles) on a chromosome. The adeno-associated virus, serotype 9 (AAV9) carries a mini-dystrophin gene.
A letter dated May 7, 2024, from the Parent Project Muscular Dystrophy organization was sent to the boy’s family expressing its deepest sympathy to those close to the boy’s care. The letter, also listed on its website, explained that Pfizer does not have full information and is working closely with trial investigators to determine the cause of the boy’s death. Other long-term studies associated with the gene therapy, such as Phase III study (NCT05689164) will continue. As part of its public acknowledgement Pfizer also stated that an incident of cardiac arrest occurred during the DAYLIGHT Phase II study.
The primary analysis for this study is anticipated after participants complete their visits by week 52 this year and fully complete the visits by January of 2029. The participants will be followed for a five-year period after receiving the gene therapy. The death discussed in this instance is apparently the second death associated with Pfizer’s gene therapy within the last few years. See Phase Ib (NCT03362502). That hold was lifted in April 2022 after announcing that ascending dosing may continue in the non-randomized study. Pfizer’s DMD gene therapy staff expressed a commitment to the well-being and safety of patients in its clinical trials as their highest priority.
Sarepta Therapeutics Elevidys® was FDA approved in June of 2023 to treat ambulatory patients aged four through five years with DMD and a mutation in the DMD gene. Other drug developers have experienced the death of young patients in clinical therapy trials.
Pat Furlong, Parent Project Muscular Dystrophy CEO, wrote on the group’s website that the organization grieves this loss and no words can describe the unjust nature of this tragedy.
