- Pfizer has reached a major milestone in its development of a gene therapy for Duchenne muscular dystrophy, announcing Thursday that researchers treated the first patient in a late-stage study the company set up early last year.
- The boy, who received his infusion of Pfizer's gene therapy on Dec. 29 at a study site in Barcelona, Spain, is the first Duchenne patient to receive a gene therapy in a Phase 3 trial. The trial's progress puts Pfizer slightly ahead in late-stage development of a gene therapy for the disease, as rival Sarepta Therapeutics has yet to begin Phase 3 testing of its product.
- Sarepta, which soon expects to disclose data from a mid-stage study of its Duchenne gene therapy, plans to conduct a small trial using a new test to measure its treatment's strength before launching its own Phase 3 trial. The Cambridge, Massachusetts-based biotech may, however, be able to discuss an accelerated approval with regulators in the U.S. using results from the mid-stage study and the small trial together.
Pfizer and Sarepta have been pushing hard to develop a one-and-done treatment for Duchenne, an inherited condition that progressively robs patients, usually boys, of their ability to walk and breathe. Both companies' therapies aim to replace the faulty gene responsible and enable patients' bodies to produce a modified version of the key muscle-building protein, dystrophin, that's otherwise lacking.
Sarepta's key advantage is that the company is already deep into a randomized trial evaluating its gene therapy, SRP-9001, against a placebo to test whether the treatment slows disease progression. The Phase 3 trial Pfizer has just started, meanwhile, is the company's first placebo-controlled test of its therapy.
But Pfizer's study is the first to test a Duchenne gene therapy product that's been produced using commercial-scale manufacturing lines, a key step in the quest to gain approval. Sarepta expects to do the same with a Phase 3 trial planned for this year, but it will first launch a smaller, 10-patient test to assess its commercial-scale product. That trial will use a new "potency" assay to evaluate SRP-9001, a step the FDA requested.
On a call with investors in November, Sarepta CEO Doug Ingram suggested data from the company's initial placebo-controlled trial plus safety and expression results from the small commercial trial could be enough to support a regulatory submission in the U.S.
As DMD often leads to an early death, regulators may be sympathetic to accelerated consideration of Sarepta's therapy. Ingram, however, noted the company would discuss such a path with the FDA after obtaining the data.
Both Sarepta and Pfizer use adeno-associated viruses to deliver a shortened version of the genetic code that stimulates production of dystrophin. A gene therapy that could slow disease progression in Duchenne would be a major improvement over current standard of care, led by Sarepta's drugs Exondys 51 and Vyondys 53, which treat only patients with specific mutations.
Both gene therapies have shown promise, though they were tested in slightly different age groups. Sarepta's results to date are in boys 4 to 7 years old, while Pfizer has been testing its gene therapy in 6 to 12 year olds, who are more likely to have started declining from the disease.
In its Phase 3 study, however, Pfizer plans to enroll 99 younger boys, aged 4 to 7, who can still walk. The trial will take place across 55 sites in 15 countries, and the primary measure of success is change from baseline on a specialized test for motor function after one year. Patients will be tracked for a total of five years after treatment.
One-third of patients enrolled into the trial will receive placebo initially. After one year, they will receive the gene therapy while the other two-thirds will be given placebo, Pfizer said. Gene therapy product will be supplied from Pfizer's manufacturing plant in Sanford, North Carolina.
A company spokesperson said an interim analysis of the trial should occur in early 2022, and Pfizer will decide whether to submit its gene therapy for approval then.