Dosing Begins in Phase 3 Trial of Pfizer’s Gene Therapy for Duchenne

The first boy has been dosed in a Phase 3 trial testing Pfizer‘s gene therapy, PF-06939926, in treating Duchenne muscular dystrophy (DMD).

“The initiation of our pivotal trial, which is the first Phase 3 DMD gene therapy program to begin enrolling eligible participants, is an important milestone for the community because there are currently no approved disease-modifying treatment options available for all genetic forms of DMD,” Brenda Cooperstone, MD, chief development officer at Pfizer Global Product Development, said in a press release.

Called CIFFREO (NCT04281485), the trial will evaluate the therapy’s safety and efficacy in up to 99 boys with DMD who are able to walk independently, ages 4 to 7. Recruitment is opening at select sites in Italy, Israel, and Spain; information is available here. A total of 55 sites in 15 countries are planned to take part.

The study’s primary endpoint, or main objective, is changes in North Star Ambulatory Assessment (NSAA) scores at one year after treatment. The NSAA, a 17-item test of motor function, is a standard measure of DMD severity in children.

Patients will be randomly assigned to either a single intravenous (IV) infusion of PF-06939926 in the study’s first year or to a placebo infusion. These groups with switch in its second year, with those treated now getting a single placebo infusion, and those initially given a placebo now receiving the gene therapy. Nearly two-thirds of the boys will be randomized to the gene therapy at the study’s start.

Eligible patients need to be on daily glucocorticoid treatment — prednisone, prednisolone, or Emflaza (deflazacort) — for at least three months prior to enrolling. They will continue with these daily therapies for the trial’s first two years.

Participants will continue to be monitored for five years after treatment with PF-06939926.

“We believe our gene therapy candidate, if successful in Phase 3 and approved, has the potential to significantly improve the trajectory of DMD disease progression, and we are working with worldwide regulatory authorities to initiate this program as quickly as possible in other countries,” Cooperstone said.

Using a modified and harmless adeno-associated virus as a vector (AAV9), the experimental gene therapy inserts a shorter-but-functional copy of the DMD gene — the faulty gene at the heart of the disorder — into patients’ muscle cells. The cells read the instructions carried on this therapeutic gene to produce “mini-dystrophin,” a stripped-down but fully working version of the needed dystrophin protein.

A single dose of PF-06939926 administered directly into the bloodstream is expected to slow or stop the muscle wasting characteristic of DMD.

The U.S. Food and Drug Administration (FDA) recently awarded PF-06939926 fast track status based on positive results — such as sustained production of the mini-dystrophin protein in muscle tissues and motor function improvements — in an ongoing Phase 1b trial (NCT03362502) in boys and men with DMD. This designation helps to speed clinical development, regulatory review, and market entry upon approval of treatments with a potential to address serious conditions.

The FDA also granted the therapy rare pediatric disease designation and, together with its European counterpart — the European Medicines Agency — orphan drug status. These designations bring additional development and marketing incentives to potential treatments for rare disorders.

“The initiation of this study is an important step forward for this community,” said Silvia Avila, president of Duchenne Parent Project Spain, “and it fuels us with hope that one day there may be treatment options for boys impacted with this devastating disease.”