Prof. Johnny Malangu (Johannesburg/ ZA), Prof. Annette von Drygalski (San Diego, CA/ US), Dr. Susan Shapiro (Oxford/ GB), Dr. Sheng-Chieh Chou (Taipei/ TW), Prof. Margareth Ozelo (Campinas/ BR), Prof. Gili Kenet (Tel Aviv/ IL), Prof. Flora Peyvandi (Milan/ IT), Dr. Bella Madan (London/ GB), Prof. Michael Laffan (London/ GB), Dr. Amy L Dunn (Columbus, OH/ US), Dr. Jane Mason (Brisbane/ AU), Dr. Doris V. Quon (Los Angeles, CA/ US), Prof. Andrew D Leavitt (San Francisco, CA/ US), Prof. Dr. Johannes Oldenburg (Bonn/ DE), Prof. Herve Chambost (Marseille/ FR), Prof. Mark T Reding (Minneapolis, MN/ US), Kala Jayaram (Novato, CA/ US), Hua Yu (Novato, CA/ US), Tara Robinson (Novato, CA/ US), Steven Pipe (Ann Harbor, MI/ US)
Background
Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) provides endogenous factor VIII (FVIII) production to prevent bleeding in people with severe hemophilia A. The aim is to evaluate outcomes 3 years after receiving valoctocogene roxaparvovec.
Methods
The open-label, multicenter phase 3 GENEr8-1 trial (NCT03370913) evaluated 6x1013 vg/kg valoctocogene roxaparvovec in 134 adult men with severe hemophilia A (FVIII ≤1 IU/dL) without inhibitors. Bleeds and FVIII use were self-reported after regular prophylaxis ended (scheduled for week [W] 4) through data cutoff. Comparisons to baseline on FVIII prophylaxis were performed in 112 HIV-negative participants enrolling from a non-interventional study (rollover population). FVIII activity per chromogenic assay and quality of life (QOL) per Haemo-QOL-A were assessed in 132 HIV-negative participants (modified intent-to-treat [mITT] population). Safety was assessed in all participants.
Results
Median follow-up was 162 weeks (N=134); 131 participants completed W156. Over 3 years in 112 rollover participants, mean annualized treated bleeding rate was 0.8 bleeds/year, mean annualized rate of all bleeds was 1.3 bleeds/year, and mean FVIII utilization was 125 IU/kg/year (Table). During Y3, 73.2% of 110 rollover participants had 0 treated bleeds and 61.6% had no bleeds. At W156, mean and median FVIII were 18.8 and 8.4 IU/dL (mITT, N=132; Figure); Overall, 10/132 (7.6%) participants resumed prophylaxis. Mean Haemo-QOL-A Total Score change from baseline to W156 was +6.6 (n=122; P <0.0001). No new safety signals emerged. In Y3, 34/134 participants (25.4%) had alanine aminotransferase (ALT) elevation.
Conclusion
Valoctocogene roxaparvovec provided robust hemostatic efficacy relative to FVIII prophylaxis for 3 years, with QOL improvement and stable safety.
Offenlegung Interessenkonflikt:
Johannes Oldenburg received research support from Bayer, Biotest, CSL-Behring, Novo Nordis, Octapharma, Pfizer, Takeda; advisor for Bayer, Biogen Idec, BioMarin, Biotest, Chugai, CSL-Behring, Freeline, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche, Spark, Swedish Orphan Biovitrum, Takeda; lecturer at Bayer, Biogen Idec, BioMarin, Biotest, Chugai, CSL-Behring, Freeline, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche, Spark, Swedish Orphan Biovitrum, Takeda; travel support from Bayer, Biogen Idec, Biotest, Chugai, CSL-Behring, Freeline, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche, Spark, Swedish Orphan Biovitrum, Takeda