In patients with severe hemophilia A and a history of high inhibitor titers, the use of a recombinant factor VIII (FVIII) Fc fusion protein (rFVIIIFc) was associated with a rapid time to tolerization and was well tolerated in a recent phase 4 study. Results from the final analysis of this study were reported in the journal Blood.
The prospective, single-arm verITI-8 study (ClinicalTrials.gov Identifier: NCT03093480) enrolled male patients with severe hemophilia A and high inhibitor titers, based on a historical peak of ≥5 Bethesda units/mL.
Patients were screened and given immune tolerance induction (ITI) using rFVIIIFc dosed at 200 IU/kg/day until tolerization, for a maximum duration of 48 weeks. Upon reaching successful ITI status, patients were tapered to a standard prophylactic dose and began follow-up.
The study had a primary endpoint of time to tolerization using rFVIIIFc. This was characterized by reaching an inhibitor titer <0.6 Bethesda units/mL, an incremental recovery (IR) that was ≥66% of the expected IR, and tolerance of the agent as reflected by reaching a half-life of ≥7 hours during the 48-week period.
There were 16 patients who received at least 1 dose of rFVIIIFc in this study, and they had a median age of 2.1 years at the start of the study. Negative inhibitor status was reached in 12 patients (75%), with this marker of ITI success reached at a median of 7.4 weeks (interquartile range [IQR], 2.2-17.8).
An IR of ≥66% of the expected IR was attained by 11 patients (69%), with this marker reached at a median of 6.8 weeks (IQR, 5.4-22.4). A half-life of ≥7 hours within 48 weeks was attained in 10 patients (63%), at a median of 11.7 weeks (IQR, 9.8-26.2).
Treatment-emergent adverse events (TEAEs) occurred in all patients. The researchers reported 1 related TEAE involving injection site pain that was considered mild. There were serious TEAEs in 9 patients, but none were deemed related to the study drug. There were no deaths, thrombotic events, serious allergic reactions, or discontinuations due to adverse events reported.
“In conclusion, the final data from verITI-8 demonstrate benefit of rFVIIIFc as first-time ITI to eradicate inhibitors in patients with severe hemophilia,” the researchers concluded in their report. They also highlighted a rapid time to tolerization in this study, and with durable responses seen in nearly two-thirds of the patients.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.
Malec L, Van Damme A, Chan AKC, et al. Recombinant factor VIII Fc fusion protein for first-time immune tolerance induction: final results of the verITI-8 study. Blood. 2023;141(16):1982-1989. doi:10.1182/blood.2022017780