- The Food and Drug Administration has placed a clinical hold on Pfizer's gene therapy to treat Duchenne muscular dystrophy, following the death of a patient in a Phase 1 clinical trial. Pfizer announced the death Monday, revealing few details "out of respect for the patient and his family’s privacy."
- Pfizer said it has incomplete information but is "actively working with the trial site investigator to understand what happened." The news comes just a few months after Pfizer modified the design of a Phase 3 trial aimed at supporting FDA approval due to side effects involving muscle weakness and heart inflammation.
- The hold is another safety setback in the effort to create a one-time treatment for Duchenne muscular dystrophy, an inherited disease that leads to loss of mobility and early death. Pfizer, alongside Sarepta and Solid Biosciences, have been leading the development of therapies, but side effects and disappointing efficacy have slowed progress.
Gene therapy revealed itself more than three years ago as a promising strategy for treating DMD. But the years since have raised questions and new safety worries as companies developing the treatments moved further into testing.
Solid has seen its progress slowed by safety concerns, while Sarepta's first data from a trial that compared its gene therapy to a placebo failed to show significant improvement in patients' motor function. Now, Pfizer, the first company to initiate a Phase 3 trial that could earn regulatory approval, has twice dealt with safety concerns in the past year.
Pfizer had just re-started work on its Phase 3 trial, which was slowed by cases of muscle weakness that the company attributed to an immune response to the protein encoded by its gene therapy. The side effect could be avoided, Pfizer claimed, by ensuring patients with a certain genetic profile don't receive the therapy.
Without more details on the patient's death, it's likely Pfizer and regulators won't be able to determine its impact on further study of the company's therapy — or, potentially, other developers' — for some time.
That leaves significant uncertainty for the DMD community, which has successfully organized to campaign for greater research and investment in experimental medicines like gene therapy. So far, however, the new drugs that have recently become available, from Sarepta and NS Pharma, are at best only modestly effective and work in only a minority of DMD patients.
"We must continue to invest in genetic therapies because of the science and possibilities, but we must do with blinders removed from our hearts and minds," Pat Furlong, CEO of Parent Project Muscular Dystrophy, wrote in a letter to its membership following Pfizer's announcement.
Gene therapy safety, in DMD and beyond, has recently come under more intense scrutiny after concerning side effects cropped up in trials. The FDA recently convened a meeting of outside experts to more thoroughly review potential risks, although there was no clear support for limiting research significantly in response.