A year later to maintain FVIII activity levels Pfizer haemophilia A gene therapy updated phase 1/2 results

On December 7, Pfizer and gene therapy company Sangamo Therapeutics jointly announced at the 62nd annual meeting of the American Society of Hematology (ASH) the latest follow-up data for the 1/2 clinical study Alta for patients with severe haemophilia A, including data on patients with the longest treatment time of 85 weeks.
results showed that five patients in the high-dose 3x1013vg/kg queue who were receiving the gene therapy were followed for at least one year, and all patients maintained consistent levels of human coagulation factor VIII (FVIII).
color analysis showed that from week 9 to week 52, the median FVIII activity in the treatment group was 56.9% and the geometric average FVIII activity was 70.4%.
addition, all patients receiving a dose queue of 3×1013vg/kg achieved stable FVIII activity within 9 weeks of treatment and no bleeding events and FVIII infusion requirements during the first year.
as of August 31, 2020, a patient with targeted joint bleeding required FVIII treatment, but the case also occurred after week 52.
Alta study is an open label, dose range, multi-center Phase 1/2 clinical trial designed to assess the safety and tolerability of giroocotogene fitelparvovec in patients with severe haemophilia A.
11 male patients with an average age of 30 years (range 18-47 years) were assigned to four dose groups (9x1011 vg/kg, 2 patients; 2 x 1012 vg/kg, 2 patients, 1x1013 vg/kg, 2 patients; 3 x 1013 vg/kg, 5 patients).
after a year of follow-up of all patients in the study, participants were evaluated every six months until they entered the long-term follow-up study.
study also showed that giroocotogene fitelparvovec was generally well-to-do.
As mentioned earlier, only one patient in the 3 x 1013 vg/kg dose queue experienced serious adverse treatment-related events, including hypotension (level 3) and fever (stage 2), accompanied by headache and tanthea, which appeared 6 hours after the injection of the drug and were completely eliminated within 24 hours.
as of 31 August, no other serious adverse treatment-related events were reported.
but Pfizer also noted that of the five patients in the 3 x 1013 vg/kg dose queue, 4 were treated with corticosteroids to raise levels of liver enzymes (alanine transaminase, ALT).
3 patients subsequently showed elevated ALT in response to corticosteroids.
All seizures of elevated alanine amino transferase were completely resolved by oral corticosteroids, and as of August 31, no participants in the trial had used corticosteroids and no corticosteroids had been used after 52 weeks.
and Sangamo plan to provide further follow-up data for alta studies at least two years after follow-up for all five patients in the 3 x 1013 vg/kg dose queue.
deficiency of proteins needed for normal FVIII in patients with haemophilia A, spontaneous bleeding, and increased risk of injury or post-surgery bleeding.
is a lifelong disease that requires continuous monitoring and treatment.
and the two drug companies believe that gene therapy in the study may become an alternative to the current onerous treatment standards for haemophilia A patients.
Pfizer and Sangamo also presented phase 3 of the study AFFINE (NCT04370054), an open-label, multi-center, one-arm study designed to assess the effectiveness and safety of a single injection of giroocogene fitelparvovec for more than 60 adult male participants with moderate to severe haemophilia A.
eligible study participants will complete at least 6 months of routine FVIII preventive treatment in a Phase 3 study (NCT03587116) to collect pre-processed data on efficacy and selected safety parameters.
the main endpoint of the study was the effect of giroocotogene fitelparvovec on patients' annualized bleeding rate (ABR) after 12 months of treatment, compared with the ABR of previous FVIII preventive alternative therapy.
secondary endpoints included the study starting to stabilize the state and the FVIII activity level 12 months after injection of giroocotogene fitelparvovec.
in the research gene therapy giroocotogene fitelparvovec contains a recombinant adeno-related virus serotype 6 vector (AAV6) to encode the complementary DNA of human FVIII missing from the B domain.
The expression box of this therapy is designed for the optimal liver-specific expression of FVIII protein and supports the high yield production of the carrier;
, the FDA has awarded the treatment to orphan drugs, fast-track and advanced treatments for regenerative medicine (RMA), and the European Medicines Agency (EMA) has awarded it the title of orphan drug.
Giroocotogene fitelparvovec is part of a global partnership between Sangamo and Pfizer for the global development and commercialization of haemophilia A gene therapy.
end of 2019, Sangamo transferred the therapy's production technology and New Drug Research (IND) application to Pfizer.
source: 1.Pfizer and Sangamo Announce Updated Phase 1/2 Results Show Sustained Factor VIII Activity Levels in 3x1013 VG/KG Cohort Through One Year Following Hemophilia A Gene Gene Therapy 2.PFIZER AND SANGAMO ANNOUNCE UPDATED PHASE 1/2 RESULTS SHOWINGED FACTOR VIII ACTIVITY LEVELS AND NO BLEEDING EVENTS OR FACTOR USAGE IN 3E13 VG/KG COHORT FOLLOWING GIROCTOGENE FITELPARVOVEC (SB-525) GENE THERAPY 3.Update for the Alta Study, a Phase 1/2 Gene Therapy Trial of Giroctocogene Fitelparvovec (SB-525) in Adults With Severe Hemophilia A。