Another Pfizer gene therapy is free of FDA hold, but delay continues

Another of Pfizer's gene therapies has been freed from an FDA clinical hold, but the study is not set to get underway immediately. 

The FDA lifted its clinical hold of a phase 3 study called Affine for the hemophilia A gene therapy giroctocogene fitelparvovec in March. But Pfizer is maintaining a voluntary pause and will resume clinical activities in a few months, the company said during first quarter earnings Tuesday.

The voluntary pause will stay in place until Pfizer has met all necessary conditions, including approval of updated study protocols by regulatory authorities, the company said. 

Pfizer and partner Sangamo Therapeutics voluntarily paused the trial of giroctocogene fitelparvovec to adjust protocol after finding the therapy may raise blood clot risk. The delay was disclosed in November 2021, when the FDA slapped a clinical hold on the study because of “factor VIII levels greater than 150% in some study participants,” according to a May 3 earnings call.

The genetic disorder hemophilia A is caused by the lack or dysfunction of clotting protein factor VIII, with normal levels of the protein factor ranging between 50% to 150%.

Pfizer recently found out about an event of below-the-knee deep vein thrombosis in a trial participant with high factor VIII levels. The patient had a history of thrombotic events before the study, which is a known risk factor and reason for exclusion from Affine. This, along with missed doses of investigator-prescribed direct oral anti-coagulants, was investigated to determine the contributing factors to the thrombosis event, Pfizer said. The patient is reported to be doing well.

Following the FDA lift in March, Pfizer believes the study will resume in the third quarter of this year and anticipates results to go public in the second half of 2023.

Analysts from RBC Capital Markets called the lift of the FDA's clinical hold a "clear positive" for Sangamo, which has struggled in recent months as its Big Pharma partners trimmed or delayed programs. Sanofi scrapped a deal with the biotech on personalized cell therapies in January to shift focus to allogeneic universal genomic medicine approaches.


The clinical hold and resulting delay for the hemophilia gene therapy sets Pfizer behind CSL Behring and BioMarin, which both intend to submit hemophilia treatments for regulatory approval before mid-year.

Pfizer still has a robust portfolio of investigational therapies that have the potential to treat all people with hemophilia, with several clinical trials anticipated to read out in 2023, Mikael Dolsten, M.D., Ph.D., chief scientific officer and president of worldwide research, development and medical at Pfizer, said during the earnings call.

Other investigational therapies include marstacimab, a novel non-factor treatment candidate with a fast-track designation from the FDA for hemophilia A and B with inhibitors. The portfolio also includes separate gene therapy candidates for Hemophilia A and B.  

Last week, Pfizer reported that a gene therapy for Duchenne muscular dystrophy was also getting back on track after the FDA lifted a clinical hold. That therapy, called fordadistrogene movaparvovec, was placed on hold after a patient death late last year. Pfizer provided an updated potency assay and implemented a protocol amendment to monitor patients more closely.