- The Food and Drug Administration has cleared Pfizer to resume a late-stage trial of its experimental gene therapy for Duchenne muscular dystrophy following an investigation into certain safety concerns, including the death of a study participant, that led the regulator to suspend the program in December.
- Pfizer has added new safeguards to its trial as part of an agreement with the FDA to restart testing, according to a Thursday statement. After treatment with Pfizer’s gene therapy, patients must now stay in a hospital for a week and be closely monitored.
- Pfizer has also resolved issues the FDA had with a new lab test the company developed to judge the gene therapy’s potency. Enrollment has already restarted at certain international testing sites and should fully resume by June, pending feedback from other regulators. If results are positive, Pfizer could seek U.S. approval by the end of next year, a spokesperson told BioPharma Dive.
Pfizer’s program, as well as a rival treatment from Sarepta Therapeutics, are among the most closely watched in all of gene therapy research.
Both are in the final stages of testing and have shown they can help Duchenne patients produce a shortened version of the shock-absorbing protein, dystrophin, that they lack. Those findings have raised hope that each could change the course of a progressive and deadly disease that typically leaves patients in a wheelchair by their teenage years and kills them at a young age.
Yet, each program has had notable setbacks. Sarepta’s treatment, for instance, fell short of expectations in a Phase 2 study, erasing the company’s plans to seek a speedy approval from U.S. regulators in 2021. Though Sarepta executives earlier this year mentioned the company still might seek an accelerated approval, they expect to need Phase 3 data before filing an application. Those results are expected in 2023.
Pfizer’s treatment, meanwhile, has been dogged by safety concerns. In September, the company changed the design of its Phase 3 trial after three study volunteers experienced serious side effects including muscle weakness. Three months later, a participant in an earlier, Phase 1 trial died after going into cardiogenic shock, a condition in which the heart can’t pump enough blood.
Pfizer executives have said the patient who died had more advanced disease than those involved in its Phase 3 trial, and that there was evidence of underlying heart damage and a viral infection. The study volunteer was also the first treated with an immunosuppressive regimen that includes the drug Rapamune, which isn't being used in the late-stage trial.
Nonetheless, Pfizer immediately stopped testing, and the FDA later suspended the program altogether while an outside group of trial monitors reviewed the data.
Since that time, regulators in five countries have cleared Pfizer to resume its trial. The FDA has now followed, but called for new safeguards — most notably, for study investigators to closely monitor patients in a hospital for at least a week after treatment.
That requirement separates Pfizer’s gene therapy from Sarepta’s, which hasn’t been associated with serious safety concerns. It also places another restriction on the treatment, following Pfizer’s decision to exclude from clinical testing patients with genetic mutations that put them at higher risk of heart inflammation. People with those mutations represent about 15% of the Duchenne population.
Pfizer is working with its trial monitors to determine the next steps for its gene therapy in more advanced Duchenne patients who have lost the ability to walk. Its Phase 3 trial involves participants who can still walk and are between 4 and 7 years old.