Pfizer pauses Duchenne gene therapy trial after patient death

Young lonely man in a wheelchair on a balcony looking at the nature in the spring

Pfizer has called a halt to a clinical trial of its gene therapy for Duchenne muscular dystrophy as it investigates the unexpected death of a young male patient.

In an update posted today the pharma giant said "we do not yet have complete information and are actively working with the trial site investigator to understand what happened."

In the meantime, it is pausing screening and dosing of the fordadistrogene movaparvovec (PF-06939926) gene therapy, and working with the trial's data monitoring committee to try to establish whether the death is related to the drug.

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

The pause – which has been accompanied by a clinical hold imposed by the FDA – applies to a phase 1b trial that was testing the ability of the adeno-associated virus (AAV) based therapy to deliver and express  a truncated version of the gene coding for dystrophin, a protein which is deficient in DMD.

AAV vectors are well-suited to gene therapies for DMD because they are effective at targeting muscle tissue.

The death was seen in a patient in the non-ambulatory arm of the study, which involves patients who are more severely affected by the muscle wasting disease.

Pfizer added the gene therapy to its pipeline in 2016, when it acquired Bamboo Therapeutics in a deal worth up to $645 million.

The safety of gene therapies has been in the spotlight in the past few years, with several therapies using AAV as well as other viral vectors placed on hold by regulators while potential side effects are investigated.

There has been speculation that the AAV vectors may activate the complement system, leading to inflammation in tissues.

Pfizer's two closest rivals in the DMD gene therapy space – Sarepta and Solid Biosciences – have both had their AAV-based gene therapies for DMD temporarily placed on clinical hold in the past, but were able to restart testing.

Pfizer meanwhile has had other scares about the safety of its gene therapy, including most recently reports of muscle weakness and myocarditis in some patients who received the gene therapy, which seem to be linked to certain genetic mutations affecting exons 9 to 13, and 29 and 30.

Its pivotal CIFFREO trial – which is being conducted in ambulatory patients who are able to walk – has been modified to exclude patients with these mutations, and at the moment it is unclear whether it will be affected by the clinical hold.

Recruitment into CIFFREO in the US has been delayed in the US by an FDA request for potency, but is already underway elsewhere, including in Europe and Asia. Pfizer has been talking about having interim data from the trial in the third quarter of next year.

Sarepta meanwhile is running the EMBARK phase 3 study of SRP-9001, and expects to fully enrol the trial in the first half oof 2022.

Solid Bio said recently it has started dosing additional patients in its phase 1/2 trial of SGT-001 – called IGNITE DMD – and will have further results from the first three patients treated with the therapy next year.