• ClinicalTrials.gov Identifier: NCT04370054¹
• Phase III AFFINE trial (NCT04370054)^1, 2

• Active, not recruiting
• Last Update Posted: 2024-07-24

• Males who have been followed on routine Factor VIII prophylaxis therapy during the lead-in study (C0371004) and have > = 150 documented exposure days to a Factor VIII protein product
• Moderately severe to severe hemophilia A (Factor VIII activity < =1%)
• Suspension of FVIII prophylaxis therapy post study drug infusion

• Anti-AAV6 neutralizing antibodies
• History of inhibitor to Factor VIII
• Laboratory values at screening visit that are abnormal or outside acceptable study limits

AAV6³, Baculovirus insect cell line³

 B domain deleted human FVIII transgene⁴

The SB-525 expression cassette includes a liver-specific promoter module with multi-factorial modifications and a synthetic polyA signal as regulatory vector elements⁵

    Systemic delivery through a single intravenous infusion (IV)⁴

Single dose cohort: 3e13 (76)¹

From Week 12 to at least 15 months²

Not yet reported

84% of participants maintained FVIII activity above 5% at 15 months post-infusion, with most participants  exhibiting levels of 15% or higher²

Not yet reported

Statements about the ABR after gene therapy, compared to the pre-infusion period, were collected from here² and summarized as follows:   

• From week 12 at least 15 months [15–44 months]):
  • Giroctocogene fitelparvovec demonstrated statistically significant 74% reduction in mean total ABR compared to the pre-infusion
    period (1.24 vs. 4.73) following a single 3e13 vg/kg dose
  • The mean treated ABR showed a statistically significant 98.3% reduction from 4.08 in the pre-infusion period to 0.07 post-infusion

Not yet reported

Not yet reported

Not yet reported

Not yet reported

Not yet reported

Not yet reported

Not yet reported

Not yet reported

Not yet reported

Not yet reported

1. Study to Evaluate the Efficacy and Safety of PF-07055480 /​ Giroctocogene Fitelparvovec Gene Therapy in Moderately Severe to Severe Hemophilia A Adults (AFFINE). Available at: Study Details | Study to Evaluate the Efficacy and Safety of PF-07055480 / Giroctocogene Fitelparvovec Gene Therapy in Moderately Severe to Severe Hemophilia A Adults | ClinicalTrials.gov
2. Philippidis A. Pfizer Marks Phase III Success in Hemophilia A, then Layoffs after Failure in DMD. Hum Gene Ther. 2024 Sep;35(17-18):578-581. doi: 10.1089/hum.2024.378422.tlg. PMID: 39284162. Pfizer Marks Phase III Success in Hemophilia A, then Layoffs after Failure in DMD - PubMed (nih.gov)
3. Peyvandi, F. and I. Garagiola, Clinical advances in gene therapy updates on clinical trials of gene therapy in haemophilia. Haemophilia, 2019. 25(5): p. 738-746. Clinical advances in gene therapy updates on clinical trials of gene therapy in haemophilia - PubMed (nih.gov)
4. Leavitt AD, Konkle BA, Stine KC, Visweshwar N, Harrington TJ, Giermasz A, Arkin S, Fang A, Plonski F, Yver A, Ganne F, Agathon D, Resa MLA, Tseng LJ, Di Russo G, Cockroft BM, Cao L, Rupon J. Giroctocogene fitelparvovec gene therapy for severe hemophilia A: 104-week analysis of the phase 1/2 Alta study. Blood. 2024 Feb 29;143(9):796-806. doi: 10.1182/blood.2022018971. PMID: 37871576; PMCID: PMC10933705. Giroctocogene fitelparvovec gene therapy for severe hemophilia A: 104-week analysis of the phase 1/2 Alta study - PMC (nih.gov)
5. Sangamo and Pfizer Announce Updated Phase 1/2 Results Showing Sustained Increased Factor VIII Activity Through 44 Weeks Following SB-525 Gene Therapy Treatment.  December 7, 2019]; Sangamo and Pfizer Announce Updated Phase 1/2 Results Showing Sustained Increased Factor VIII Activity Through 44 Weeks Following SB-525 Gene Therapy Treatment.

AAV, Adeno-associated virus; ABR, Annualized bleeding rate; AEs: adverse events; AIR, Annualized FVIII/FIX infusion rate; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CH, Chromogenic Assay; Co., cohort; DOACs, Direct oral anticoagulants; D, days; EDs, exposure days; FIX, factor IX; FIX-Padua, gain of function FIX variant; FVIII, factor VIII; gc, genome copies; HEK cells, human embryonic kidney cells; IQR, interquartile range; IRR, Infusion-related reaction; NAbs, neutralizing antibodies; OS, One-stage clotting assay; Pop., population; pt., patient/participant; pts., patients/participants; P1, Participant 1; PI, phase I; PBGD, porphobilinogen deaminase; PBMC, peripheral blood mononuclear cells; SAEs, serious adverse events; SFU, spot-forming units; TAC, tacrolimus; ULN, upper limit of normal; VCN, vector copy number; vg, vector genomes; W, weeks; WT, wild type; Y, year