CIFFREO Trial of Potential DMD Gene Therapy Delayed in US

Steve Bryson, PhD avatar

by Steve Bryson, PhD |



Pfizer has announced a delay in opening U.S. sites for its Phase 3 clinical trial CIFFREO, evaluating the investigational gene therapy PF-06939926 in boys with Duchenne muscular dystrophy (DMD).

The delay is caused by questions from the U.S. Food and Drug Administration (FDA) regarding the company’s investigational new drug application, which was submitted to ask for permission to run the trial. 

Specifically, the questions focused on technical aspects of the company’s potency tests, which are used to measure the potential therapy’s ability to elicit a specific response at a selected dose. 

Pfizer is working to resolve the delay, but it does not expect a resolution in the first half of this year. 

“While we have high confidence in our current quality control overall and with our potency assays, which have been accepted in countries outside of the U.S., the FDA has additional technical requests that we are working to address as quickly as possible,” Pfizer said in an update to the Duchenne community.

CIFFREO (NCT04281485) is enrolling up to 99 boys with DMD, ages 4 to 7, who can walk independently. The trial has opened at 14 selected sites in the U.K., Italy, Spain, Israel, South Korea, Japan, and Russia.

The company also announced it now is recruiting in Canada at Children’s Hospital — London Health Sciences Centre in London, Ontario. For contact information, click here or email: [email protected].

“Our community remains hopeful for what the future may bring, and we are thankful for all the families that continue to donate their time and accept potential risks in the pursuit of advancing science and finding treatments for all boys and young men living with Duchenne,” Nicola Worsfold, director of research and advocacy at Jesse’s Journey, said in a press release.

Jesse’s Journey is a Canadian charity dedicated to raising funds for research related to DMD. The organization is dedicated to DMD patient Jesse Davidson, and began in the summer of 1995 when Jesse’s father John pushed his 15-year-old son more than 2,000 miles across Ontario in his wheelchair to raise awareness and funding. 

PF-06939926, which now has the approved generic name fordadistrogene movaparvovec, is a gene therapy designed to bring a mini-dystrophin gene into muscle. People with Duchenne have a deficiency in the protein dystrophin due to mutations in the DMD gene. Dystrophin provides protection and structural support for muscle fibers.

The mini-gene, delivered by a harmless, modified adeno-associated virus as a vector (AAV9) administered directly into the bloodstream, carries the instructions for a short, yet functional, dystrophin protein which is expected to slow or halt the muscle degeneration of DMD.

CIFFREO’s primary goal is a change in participants’ overall motor function, as assessed by the 17-item North Star Ambulatory Assessment, one year after treatment. 

Before enrollment, participants are required to be on a stable, daily regimen of glucocorticoids such as prednisone, prednisolone, or Emflaza (deflazacort) for at least three months. 

Secondary outcomes include the level and distribution of the mini-dystrophin protein as assessed by muscle biopsy, as well as biomarkers and additional functional tests. Nearly one-third of the boys will receive a placebo at study start and PF-06939926 one year later. Patients will be monitored for five years after their single gene therapy dose.

In March, the company reported on the ongoing Phase 1b study (NCT03362502) evaluating the safety and tolerability of PF-06939926 in DMD boys who can walk. The therapy demonstrated the potential for substantial benefits with an acceptable safety profile. 

“We want to thank the Duchenne community for your trust and collaboration and assure you that we are working as quickly as we can to bring this potential treatment to patients,” Pfizer stated in its update.