Dosing paused in Pfizer DMD gene therapy trial after patient death

Investigators seeking to determine if boy's death was related to treatment

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Dosing has been paused in a Phase 3 trial testing fordadistrogene movaparvovec in children with Duchenne muscular dystrophy (DMD) following the sudden death of a boy who had been previously treated with the gene therapy, its developer Pfizer announced in a letter to the community.

Pfizer indicated it does not have complete information about the circumstances of the boy’s death and is working closely with trial investigators to understand what happened. It is not established whether the death was related specifically to the gene therapy.

Aside from the pause in dosing, trial activities are “continuing as scheduled,” stated the letter, signed by the Pfizer DMD gene therapy team.

“The safety and well-being of the patients in our clinical trials remains our top priority, and we are committed to sharing more information with the medical and patient community as soon as we can,” the letter stated.

“We are also aware that many in the patient community are hopeful about the potential benefit of fordadistrogene movaparvovec for the treatment of DMD, and we will continue to collect data from our trials to evaluate its ability to address this disease,” Pfizer said.

DMD is caused by mutations in the gene encoding dystrophin, a protein important for muscle health. Via a one-time infusion into the bloodstream, fordadistrogene movaparvovec intends to deliver a gene encoding production of a shortened but functional dystrophin protein into muscle cells.

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The patient who died was participating in the Phase 2 DAYLIGHT trial (NCT05429372), which is evaluating the safety and tolerability of fordadistrogene movaparvovec in 10 boys with DMD, ages 2-3. The boy was dosed with the one-time gene therapy in early 2023.

“We are [devastated] to learn of this heartbreaking loss and our hearts are with the boy’s family during this unimaginably difficult time,” Debra Miller, founder and CEO of CureDuchenne, a nonprofit advocacy organization, said in a statement emailed to Muscular Dystrophy News Today.

“This tragic event painfully reminds us of the stakes of our mission and the importance of ensuring the utmost safety in all clinical trials. … We recognize the tremendous courage of this family — and all families that participate in clinical trials — as we offer the support of the whole Duchenne community,” Miller said.

While Pfizer works with regulators and an external data monitoring committee to understand what happened, the company is pausing dosing in the ongoing CIFFREO Phase 3 trial (NCT04281485) that’s testing the gene therapy in boys with DMD, ages 4-7.

Although dosing in the first placebo-controlled portion is complete, the company is putting a hold on dosing in its crossover portion, in which patients initially assigned to the placebo would receive the gene therapy.

Other than the dosing pause, other trial activities will proceed as scheduled, and patients who have already received treatment will continue to be monitored, according to Pfizer. The pause will not affect other trials in the fordadistrogene movaparvovec program, where dosing is already complete.

That includes DAYLIGHT as well as a Phase 1b trial (NCT03362502) that enrolled boys with DMD, ages 4-12. A long-term extension study (NCT05689164) designed to follow previously treated patients from these studies over a 10-year period, also will continue.

Dosing in fordadistrogene movaparvovec trials was similarly paused in late 2021 after the death of a 16-year-old boy who was participating in the Phase 1b study. The hold was lifted in 2022 with certain protocol amendments.

Data from the Phase 1b trial have shown that the gene therapy helped preserve function and increase muscle volume in boys with DMD, especially among the youngest study participants.

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Parent Project Muscular Dystrophy, another nonprofit advocacy organization, said in an update on its website that it was “imperative” for the community to join together in support of one another.

“The loss of any member of our community is deeply felt, and our hearts ache with the family and loved ones of this courageous young child, whose bravery and commitment to advancing research for Duchenne will forever be remembered and honored,” said Pat Furlong, the organization’s president and CEO.

“This journey is not without its challenges, and yet, it is also instilled with resilience, determination, and unwavering hope. In the face of adversity, we find the courage to persevere, fueled by the knowledge that every step forward brings us closer to our shared goal of ending Duchenne,” Furlong added.

Pfizer also extended its sympathies to the boy’s “family, friends, and those closest to his care.”