Pfizer and Sangamo Announce Positive Phase 1/2 Results for Giroctocogene Fitelparvovec in Severe Hemophilia A

Compiled by Keke

On June 18, Pfizer and Sangamo Therapeutics announced the latest progress data from the Phase 1/2 clinical study Alta of the investigational gene therapy giroctocogene fitelparvovec (SB-525 or PF-07055480) for the treatment of patients with severe hemophilia A. The data showed that all five patients with severe hemophilia A who received a dose of 3e13 vg/kg of giroctocogene fitelparvovec demonstrated sustained factor VIII (FVIII) activity levels, with a median value of 64.2% as measured by chromogenic assay (average FVIII levels in patients nine weeks after infusion). No bleeding events were reported among the patients, nor did any require FVIII injections. The factor VIII activity levels reflected observation periods of up to 61 weeks, which was the longest follow-up duration for treated patients in this cohort.

Meanwhile, giroctocogene fitelparvovec was generally well tolerated. Consistent with previous studies, one patient in the 3e13 vg/kg dose group experienced treatment-related serious adverse events of hypotension (Grade 3) and fever (Grade 2), accompanied by headache and tachycardia. These symptoms occurred 6 hours after infusion and resolved completely within 24 hours. No other treatment-related serious adverse events were reported in this study. Among the five treated patients, four received corticosteroid therapy for elevated liver enzymes (alanine aminotransferase, ALT). Subsequently, three patients exhibited ALT elevations that responded to corticosteroids. All episodes of ALT elevation were fully resolved with oral corticosteroids.

Alta is an open-label, dose-ranging, multicenter clinical trial designed to evaluate the safety and tolerability of giroctocogene fitelparvovec in patients with severe hemophilia A. The study enrolled 11 patients, all male, with a mean age of 30 years (range: 18–47 years). They were assigned to four escalating dose cohorts: 9e11 vg/kg (n=2), 2e12 vg/kg (n=2), 1e13 vg/kg (n=2), and 3e13 vg/kg (n=5). The latest follow-up data build upon the Alta study results presented by Pfizer and Sangamo Therapeutics at the American Society of Hematology (ASH) Annual Meeting in December 2019. At that time, the data indicated that giroctocogene fitelparvovec was generally well tolerated and enabled patients to maintain factor VIII (FVIII) levels for up to 44 weeks (based on follow-up of the patient treated for the longest duration in the 3e13 vg/kg dose cohort). Subsequently, Pfizer and Sangamo Therapeutics planned to follow up all five patients in the 3e13 vg/kg dose cohort for at least one year.

The encouraging results of giroctocogene fitelparvovec in terms of FVIII expression levels and complete suppression of bleeding events are promising. However, beyond efficacy and safety, the long-term durability of gene therapy for hemophilia is currently another key focus. According to the latest published data, compared to the other three patients in the 3e13 vg/kg dose cohort, Patients 9 and 11 appeared to experience a more pronounced decline in FVIII activity over time; at the 61-week time point, Patient 7’s FVIII activity seemed to drop sharply, although it still remained within the range of variability observed for FVIII activity in the trial. The two companies consider it important that the mean FVIII activity in this dose cohort (from Week 9 to Week 36, n=4) remained well above 50% of normal levels. Nevertheless, the primary concern remains the durability of the therapeutic effect and the potential downward trend, although there is currently no consistent signal indicating waning efficacy.

On the 18th, BioMarin announced the latest data from its Phase 1/2 clinical study of valoctocogene roxaparvovec, a gene therapy for severe hemophilia A. The data demonstrated significant efficacy over four years of treatment, and the therapy is scheduled to undergo regulatory review for market approval this August, positioning it as the most formidable competitor to giroctocogene fitelparvovec. However, investors share concerns that the long-term relative efficacy of these two gene therapies remains uncertain as time progresses. From BioMarin’s perspective, achieving four years of protection against bleeding episodes and eliminating the need for infusions is sufficient to benefit patients eager to resume normal lives.

Currently, giroctocogene fitelparvovec has been granted Orphan Drug, Fast Track, and Regenerative Medicine Advanced Therapy designations by the U.S. FDA, as well as Orphan Drug designation by the European Union.

Reference Source: Pfizer and Sangamo Announce Updated Phase 1/2 Results Showing Sustained Factor VIII Activity Levels and No Bleeding Events or Factor Usage in 3e13 vg/kg Cohort Following giroctocogene fitelparvovec (SB-525) Gene Therapy