Can we use Altuviiio (efanesoctocog alfa) for patients who have a history of inhibitors and underwent ITI?

Answer: There is no prospective trial evidence — but the limited retrospective data are encouraging.

• XTEND-1 excluded patients with a detected inhibitor or any prior history of inhibitors, and also excluded patients on emicizumab. Enrolled patients had ≥150 exposure days.
• One retrospective study suggests it is effective — 7 patients who switched from emicizumab and 5 who previously underwent ITI:

Five patients had a history of FVIII inhibitors, and all achieved excellent hemostasis without inhibitor recurrence. One of the five initially had rapid clearance of Efa, necessitating more frequent dosing at 50 IU/kg every five days to achieve clinical goals. Longitudinal monitoring of FVIII levels revealed reduced clearance after 1 year of prophylaxis, and he returned to standard weekly dosing. We hypothesise that the structure of Efa may have shielded immunogenic epitopes, providing additional effective immune tolerance of trace persistent neutralising or clearance FVIII antibodies, leading to normalisation of half-life over time.

— Haemophilia, doi:10.1111/hae.70175

Ongoing trials to watch: XTEND-ed extension · joint health · physical activity · and, most relevant here, efanesoctocog alfa for ITI.

Source: Retrospective cohort, Haemophilia, doi:10.1111/hae.70175 — primary-literature. Pivotal trial: XTEND-1, NEJM, doi:10.1056/NEJMoa2209226 (excluded this population).