Pfizer Doses First Patient in Study on Hemophilia A Gene Therapy

October 13, 2020 - Pfizer and Sangamo Therapeutics recently announced that the first patient has been dosed in the Phase 3 study of an investigational gene therapy for hemophilia A patients.

The Phase 3 AFFINE study is a global, multicenter clinical trial that will evaluate the efficacy of the gene therapy, giroctocogene fitelparvovec, in patients with moderate to severe hemophilia A.

The primary endpoint will be impact on annual bleed rate through 12 months following treatment, compared to the bleeding rate on the Factor VIII replacement therapy, which was gathered during the lead-in phase of the study, Pfizer said in the announcement. 

Patients will be analyzed for up to five years following the single infusion. 

“The initiation of the pivotal Phase 3 dosing study of giroctocogene fitelparvovec is a significant achievement for Pfizer as we continue our longstanding commitment to improving care for the hemophilia community,” Brenda Cooperstone, chief development officer of rare disease at Pfizer global product development, said in the announcement. 

“Enrollment in the lead-in study is progressing well and recruitment is on track for Phase 3. Given the Phase 1/2 study findings to date, we believe that giroctocogene fitelparvovec has the potential to sustain factor levels and reduce annual bleed rates, suggesting this one-time gene therapy could potentially transform the standard of care for eligible patients worldwide.”

Specifically,  Pfizer recently found that giroctocogene fitelparvovec was generally well tolerated in patients in a Phase 1/2 study. Each of the five patients in the high dose cohort sustained FVIII activity levels without bleeding or prophylactic factor for over two years after.

Factor VII activity levels were sustained at a “clinically meaningful level,” Pfizer said. The geometric mean was 71 percent, which measured between weeks nine and 52.

Data from the Phase 3 lead-in study will give researchers a baseline for patients evaluated in the Phase 3 study. 

The collaboration between Pfizer and Sangamo was established in 2017 and through the collaboration, Sangamo earned a $30 million milestone payment.

The company is also eligible to receive total potential milestone payments of up to $300 million for the development and commercialization of giroctocogene fitelparvovec and up to $175 million for additional hemophilia A gene therapy product candidates.

Pfizer stated that it is now operationally and financially responsible for research, development, manufacturing, and commercialization activities for giroctocogene fitelparvovec after the transfer of the investigational new drug from Sangamo to Pfizer back in 2019.

The first cell and gene therapy was approved in 2017 and the increasing rate of research and development is continuing to enhance the reality of personalized gene therapy treatments for patients in the near future.

A March Pharmaceutical Research and Manufacturers of America (PhRMA) report found that there were 362 investigational cell and gene therapies in clinical development, a 20 percent increase from 2018. 

In mid-April, FDA approved Sevenfact, a treatment for hemophilia A and B with inhibitors for adults and adolescents 12 years of age or older.

This FDA approval is important because individuals with inhibitors may not respond to factor replacement therapy. Any bleeding episodes are currently managed either on demand or via prophylaxis. 

Sevenfact is a unique treatment option for patients with the chronic disease. The product is the first hemophilia treatment containing an active ingredient obtained from rabbits genetically engineered to produce a protein for blood coagulation.

The approval was based on a clinical study of 27 patients with hemophilia A or B, which found that 86 percent of patients were treated successfully with the lower dose of 75mcg/kg and a higher dose of 225mcg/kg. The three severe bleeding episodes were treated with the higher dose.