Pfizer, Sangamo report sustained clotting factor activity, no bleeding with haemophilia A gene therapy

Pfizer and partner Sangamo Therapeutics on Thursday announced updated results from the Phase I/II Alta study of giroctocogene fitelparvovec showing that all five patients with severe haemophilia A who were given the highest dose of the AAV6-based gene therapy had sustained Factor VIII activity, with none experiencing bleeding events or requiring factor replacement infusions. Bettina Cockroft, chief medical officer at Sangamo, said the follow-up data, which were presented at the World Federation of Hemophilia (WFH) virtual conference, indicate giroctocogene fitelparvovec led to "sustained factor levels up to 14 months following treatment and suggest the potential of this investigational gene therapy to alleviate treatment burden of current haemophilia disease management."

The Alta study includes 11 male patients ranging in age from 18 to 47 years with severe hemophilia A who were enrolled across four ascending dose cohorts. Two patients each are in the 9e11 vg/kg, 2e12 vg/kg and 1e13 vg/kg cohorts, in addition to the five patients who received the 3e13 vg/kg dose of giroctocogene fitelparvovec.

Clotting factor activity at 64.2%

Pfizer and Sangamo reported that the patients in the 3e13 vg/kg dose arm showed sustained Factor VIII protein levels, with a median of 64.2% via chromogenic assay. They noted that the clotting factor activity reflects measurements up to 61 weeks, the extent of follow-up for the longest-treated patient in the group. The companies plan to present further follow-up data from the Alta trial when all five patients in the highest-dose cohort have been followed for at least one year.

Giroctocogene fitelparvovec was also generally well tolerated in the study, and aside from a previously reported case in the highest-dose cohort of treatment-related hypotension and fever, including symptoms of tachycardia, which resolved within 24 hours, the companies said no other serious adverse events related to the therapy occurred. They also reported that four patients in this dose group experienced alanine aminotransferase (ALT) liver enzyme elevations, all of which resolved with oral corticosteroids.

Phase III study start later this year

Seng Cheng, chief scientific officer of Pfizer’s rare disease research unit, said the latest Alta trial results "affirm previous findings from this Phase I/II study." He added "we are encouraged by the potential of giroctocogene fitelparvovec to demonstrate longer-term durability, an important element for patients living with severe haemophilia A." Pfizer and Sangamo said dosing in a pivotal Phase III study of the gene therapy, also known as SB-525 and PF-07055480, is slated to begin in the second half of 2020, with the primary endpoint evaluating annualised bleeding rate over 12 months in an estimated 63 patients with moderately severe-to-severe haemophilia A.

Earlier this week, BioMarin reported updated results from an ongoing Phase I/II study of valoctocogene roxaparvovec, saying that patients with severe haemophilia A treated with its experimental gene therapy saw a reduction of over 90% in bleeding episodes up to four years after infusion, although clotting protein activity levels appeared to continue a gradual decline. For related analysis, see ViewPoints: BioMarin paints a patient-friendly picture of valrox in four-year update.

BioMarin's therapy is currently under priority review at the FDA, which is expected to announce its decision by August 21.

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