A young man with Duchenne muscular dystrophy has died in Pfizer’s Phase Ib trial of its mini-dystrophin gene therapy, triggering a halt in screening and dosing — and a clinical hold imposed by the FDA. The gene therapy field remains on high alert for safety concerns surrounding AAV, the workhorse viral vehicle the majority of the field still relies on to deliver their supposed one-and-done cure, after patient deaths and hospitalizations rattled families, clinicians and drug developers alike. In particular, high doses of AAV — which is especially common among gene therapies aimed at the muscle-skeletal system — have been associated with serious side effects and spurred heated discussions. The open-label study was testing PF-06939926, Pfizer’s AAV9 gene therapy candidate, in both ambulatory and non-ambulatory patients. Pfizer had previously studied the same candidate only in ambulatory participants, i.e. those who can still walk. Safety fears have emerged in the past. Most recently, Pfizer amended the enrollment protocol for its Phase III trial — called CIFFREO — to exclude patients with certain genetic mutations, after investigators flagged severe side effects tied to those mutations. Those included three cases of muscle weakness, two of which included heart inflammation. (The company noted the investigators involved in that study outside of the US, and their respective regulatory authorities, have been notified of the most recent update.) And in 2020, researchers observed two cases of immune reaction to the treatment — specifically, complement activation leading to thrombocytopenia requiring platelet transfusion and treatment with a complement inhibitor.
For further information, see ENDPOINTS News https://endpts.com/one-of-pfizers-duchenne-gene-therapy-trials-put-on-hold-in-wake-of-patient-death-as-high-dose-aav-concerns-still-cloud-field/
