- Pfizer expects to soon reopen enrollment in a late-stage study of its experimental gene therapy for Duchenne muscular dystrophy, indicating Tuesday that a restart could be possible in the "next few months" pending regulatory feedback.
- The Phase 3 trial has been slowed by safety concerns, which led Pfizer to change its design to exclude certain patients who may be at higher risk of a type of heart inflammation. Separately, a volunteer in an earlier, Phase 1 study recently died, resulting in the Food and Drug Administration placing a regulatory hold on the treatment. Pfizer is still investigating the death and the role its treatment may have had.
- Pfizer's gene therapy is one of the most advanced in testing for Duchenne, alongside a treatment being developed by Sarepta Therapeutics. If the drugmaker is able to restart enrollment and testing as planned, it could have results by the end of next year and seek approval thereafter, provided the data are positive.
In addition to laying out expectations for trial progress, Pfizer offered new details on the patient death it disclosed in December, news of which triggered new concerns about the safety of gene therapy in treating Duchenne.
According to Mikael Dolsten, Pfizer's top scientist, the patient, a 16-year-old boy with advanced Duchenne, experienced low fluid volume and cardiogenic shock, a condition in which the heart can't pump enough blood. He was the first trial participant given an immunosuppressive drug called sirolimus as part of his treatment regimen, and had evidence of an active viral infection, Dolsten said on a conference call Tuesday.
"We're investigating how this may have contributed to the outcome," the executive added. "Additional assessment will be required to define next steps to restart the Phase 1b study in non-ambulatory patients who are more progressed in the disease."
Sarolimus is not used in the Phase 3 study testing the therapy in patients who are still ambulatory, which Pfizer hopes to restart soon. Dolsten said the drugmaker, after consulting with a monitoring committee overseeing the study, believes the safety risks are "manageable" in this group.
However, Pfizer previously asked to exclude from the trial patients with certain genetic mutations that may put them at higher risk of heart inflammation. People who meet Pfizer's criteria represent about 15% of the Duchenne population.
Gene therapy safety has been under scrutiny in the past year as unexpected or more serious side effects turned up in clinical trials across several different diseases. Last fall, the FDA convened a meeting of outside experts to discuss some of the most prominent known risks associated with a certain type of gene therapy. The agency has appeared to be closely watching ongoing studies, placing holds on a number of trials after reports of safety-related events.
In addition to Pfizer's treatment, Sarepta is advancing a Duchenne gene therapy and is enrolling a Phase 3 study that could provide results by 2023. The biotech's CEO in January suggested a faster path to a regulatory application for approval may be possible based on recently presented Phase 2 study results.