Personalized Prophylaxis with Human-Cl Recombinant FVIII in HA Patients

Background

Prophylactic therapy aims to maintain sufficient factor VIII (FVIII) plasma levels to prevent bleeding. FVIII plasma trough level and time spent above a certain threshold are mainly determined by the half-life of the FVIII concentrate and the injection interval.

Aims

A clinical study was conducted to investigate the efficacy of individually PK-tailored prophylaxis with Human-cl rhFVIII.

Methods

This prospective, open-label, multicenter phase 3b study included previously treated immunocompetent adult patients with severe hemophilia A without past or present inhibitors. Each patient started with a PK evaluation (single dose of 60 ± 5 IU/kg) followed by 1-3 months of routine prophylaxis (i.e. 30-40 IU/kg every other day or 3 times per week, Phase I) until individual PK data was analyzed. It was calculated, which dose and injection interval would theoretically result in a trough FVIII level of ≥1%. Then, prophylaxis was continued for 6 months using the individually recommended treatment scheme (Phase II).

Results

The study enrolled 66 patents from 20 centers across 8 countries. The majority of patients (62.1%) had been treated on-demand only before study entry. Their median annualized bleeding rate (ABR) was 41. Key outcomes of the personalized prophylaxis are:

• The prophylactic injection interval was extended from usually 3 times per week in Phase-I to twice per week or less in 58% of patients.

• The median dosing interval was 3.5 days.

• 73% of patients did not experience any bleeding episode.

• The mean ABR in phase-II was 1.45 (3.16 in Phase-I).

• The median weekly prophylactic dose decreased by nearly 10% compared to Phase-I.

• There were no inhibitors and related serious adverse events.

Conclusion

The data suggest that personalized prophylaxis with Human-cl rhFVIII results in a more convenient treatment for more than half of the patients with lower factor consumption and a lower ABR while remaining safe and efficacious.