Abstract Number: OC 26.1
Meeting: ISTH 2021 Congress
Background: Valoctocogene roxaparvovec transfers a factor VIII (FVIII-SQ) gene to hepatocytes using an adeno-associated virus vector, enabling endogenous FVIII production in individuals with congenital hemophilia A.
Aims: To assess efficacy and safety of valoctocogene roxaparvovec for severe hemophilia A.
Methods: A phase 3, single-arm, open-label trial (GENEr8-1, NCT03370913) enrolled adult men with severe hemophilia A (FVIII ≤1 IU/dL) on FVIII prophylaxis negative for FVIII inhibitors. Participants received a single 6×1013 vg/kg valoctocogene roxaparvovec infusion. Primary endpoint was change from baseline in median FVIII activity (chromogenic assay) during weeks 49–52 in HIV-negative participants. Secondary endpoints were change from baseline in annualized treated bleed and FVIII infusion rates for participants rolling over from a noninterventional study. Adverse events (AEs) were monitored.
Results: Overall, 134 participants (median [range] age, 30 [18, 70] years) were dosed and completed 49–52 weeks. In 132 HIV-negative participants, chromogenic FVIII activity increased by a mean (95% CI)/median of 41.9 (34.1–49.7)/22.9 IU/dL at weeks 49–52 (Figure 1).
After week 4, 89/112 (79.5%) participants experienced 0 treated bleeds vs 36/112 (32.1%) at baseline; 2/134 (1.5%) resumed prophylaxis. All 134 participants reported an AE; 22 (16.4%) reported serious AEs. Alanine aminotransferase elevations occurred in 115/134 (86%) participants; of these, 106 and 39 received corticosteroids and/or other immunosuppressants, respectively, per protocol, and 95.6% of events resolved. Other common AEs (≥30%) were headache (38%), nausea (37%), and aspartate aminotransferase elevation (35%). No participants developed FVIII inhibitors or thromboembolism. Additional data will be presented at ISTH.
Conclusions: In the largest-to-date hemophilia gene therapy trial, valoctocogene roxaparvovec yielded meaningful endogenous FVIII expression in participants with severe hemophilia A, resulting in significant decreases in bleeding and FVIII infusion.
To cite this abstract in AMA style:C Ozelo M, Mahlangu J, Pasi K, Giermasz A, D Leavitt A, Laffan M, Symington E, V Quon D, Wang J-, Peerlinck K, Pipe S, Madan B, S Key N, F Pierce G, O’Mahony B, Kaczmarek R, Lawal A, Huang M, Wong WY, Kim B, GENEr8-1 Trial Group . Efficacy and Safety of Valoctocogene Roxaparvovec Adeno-associated Virus Gene Transfer for Severe Hemophilia A: Results from the Phase 3 GENEr8-1 Trial [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/efficacy-and-safety-of-valoctocogene-roxaparvovec-adeno-associated-virus-gene-transfer-for-severe-hemophilia-a-results-from-the-phase-3-gener8-1-trial/. Accessed November 30, 2023.
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