Pfizer Plans to Restart Phase 3 Clinical Trial of DMD Gene Therapy PF-06939926

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In December last year, Pfizer announced that a patient death occurred in the bedridden cohort of the Phase Ib clinical trial evaluating the experimental gene therapy PF-06939926 for the treatment of Duchenne Muscular Dystrophy (DMD). This news has raised new concerns in the industry about the safety of gene therapy for treating DMD.

According to the statement released at that time, Pfizer is collaborating with an independent external data monitoring committee to review the data and understand what exactly happened, and has notified the U.S. FDA. Meanwhile, the FDA has also placed a hold on the clinical trial of PF-06939926.

However, Pfizer expects to reopen patient enrollment for the Phase 3 clinical trial soon. In addition to providing expectations for the trial's progress, the company also shared new details about the patient death incident disclosed in December of last year.

During a conference call on Tuesday, Pfizer's Chief Scientific Officer Mikael Dolsten said that the patient was a 16-year-old boy with advanced DMD who experienced hypovolemia and cardiogenic shock (a condition where the heart cannot pump enough blood). This patient was the first trial participant to include the immunosuppressive drug sirolimus as part of his treatment regimen and showed evidence of an active viral infection.

Mikael Dolsten said, "We are investigating what caused this situation. We will need additional assessments to determine the next steps and restart this Phase 1b study in bedridden patients with rapidly progressing conditions."

However, in the Phase 3 clinical study that Pfizer hopes to restart soon, sirolimus was not used. The study enrolled non-ambulatory DMD patients. Mikael Dolsten stated that the company consulted with the monitoring committee and believed that the safety risks in this patient population were "controllable."

However, Pfizer had previously requested to exclude patients with certain genetic mutations from the trial, as these mutations could place patients at a higher risk of cardiac inflammation. Patients meeting Pfizer's criteria account for approximately 15% of the DMD patient population.

PF-06939926 is an experimental recombinant adeno-associated virus serotype 9 (rAAV9) capsid that can deliver a truncated version of the human dystrophin gene to patients. The rAAV9 capsid was chosen as the delivery vector for gene therapy because of its potential to target muscle tissue.

Over the past year, the safety of gene therapy has been under close scrutiny due to unexpected or more severe side effects that emerged in clinical trials for multiple different diseases. Last fall, the FDA convened an external expert meeting to discuss some of the most significant known risks associated with specific gene therapies. The agency appears to be closely monitoring ongoing research and has paused some trials following reports of safety-related incidents.

In addition to Pfizer's gene therapy, Sarepta is also advancing a DMD gene therapy and is currently enrolling patients in a Phase 3 study, which may yield results before 2023. Sarepta's CEO stated in January this year that there may be an opportunity to seek a faster regulatory approval pathway based on recently published Phase 2 study results.

Reference article: Pfizer aims to restart late-stage trial of Duchenne gene therapy following safety setback