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rFVIIIFc establishes rapid tolerisation in haemophilia A with inhibitors

Presented by
Dr Lynn Malec, Versiti Blood Research Institute, WI, USA
ASH 2021
Recombinant factor VIII Fc protein (rFVIIIFc) therapy realised immune tolerance in approximately 2 out of 3 patients with severe haemophilia A and high-titre inhibitors who underwent immune tolerance induction (ITI) therapy for the first time. In addition, the agent displayed a swift time to tolerisation and no relapses occurred. These results add to the optimisation of ITI therapy with the purpose of eradicating inhibitors in these patients [1].

The international immune tolerance study (NCT00212472) showed that 40% of patients with severe haemophilia with inhibitors in the intent-to-treat population achieved immune tolerance, in a median time of approximately 22 months after rFVIIIFc treatment initiation. However, recent retrospective evidence suggested a higher success rate and rapid tolerisation in patients who underwent ITI therapy for the first time [2].

The current, global, prospective, verITI-8 study (NCT03093480) included 16 patients with severe haemophilia with inhibitors to administer first-time ITI therapy. The patients received rFVIIIFc therapy (200 IU/kg/day) for up to 48 weeks. If tolerisation was achieved within this timeframe, the patients entered a 16-week tapering period and a 32-week follow-up period. The primary endpoint was time to tolerisation. Treatment success was defined as negative Bethesda titres plus normal recovery (incremental recovery ≥66%) on 2 consecutive visits and rFVIIIFc half-life ≥7 hours. Dr Lynn Malec (Versiti Blood Research Institute, WI, USA) presented the final results.

Tolerisation was achieved in 63% of the patients in a median time of 11.7 weeks. In addition, the median time to the first negative inhibitor titre was 7.4 weeks, and the median time to normal recovery was 6.8 weeks (see Table). No relapses were observed in the patients who achieved tolerisation. Bypassing agents aPCC and rFVIIa were consumed by 25% and 31.3% of the patients during the ITI period, respectively. The median annual bleeding rates were 3.8 during the ITI period and 0.0 during the tapering and follow-up periods.

Table: Time to treatment success criteria [1]

IR, incremental recovery; ITI, immune tolerance induction

In total, 9 patients experienced at least 1 serious treatment-emergent adverse event (AE). However, none of these events was considered to be related to treatment. The serious treatment-emergent AEs included vascular device infections, contusions, and haemarthrosis. Importantly, no thrombotic events were reported.

  1. Malec L, et al. Efficacy of rFVIIIFc for First-Time Immune Tolerance Induction (ITI) Therapy: Final Results from the Global, Prospective VerITI-8 Study. LBA-5, ASH 2021 Annual Meeting, 11–14 December.
  2. Carcao M, et al. Haemophilia. 2021;27(1):19–25.


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