Targeting an elevated FVIII level using personalized rurioctocog alfa pegol prophylaxis in specific patient populations with hemophilia A: subanalysis of the randomized, phase 3 PROPEL study.

BACKGROUND

The phase 3, prospective PROPEL study demonstrated that pharmacokinetic (PK)-guided prophylaxis targeting elevated factor VIII (FVIII) troughs in patients with hemophilia A resulted in lower annualized bleeding rates (ABRs) and a higher proportion of patients experiencing zero bleeds in the second 6 months of treatment when targeting a FVIII trough of 8-12% 1-3%.

OBJECTIVE

To investigate the benefit of PK-guided prophylaxis with rurioctocog alfa pegol targeting two FVIII trough levels in specific patient subgroups in a analysis using data from PROPEL.

DESIGN

This is a analysis of data from the PROPEL study. The design and primary outcomes of the prospective, randomized PROPEL study (NCT02585960) have been reported previously.

METHODS

This analysis reports data stratified by FVIII half-life (), hemophilic arthropathy status, number of target joints at screening, previous treatment regimen, and ABR range in the 12 months before study entry.

RESULTS

Targeting an elevated FVIII trough of 8-12% was associated with higher average FVIII levels over time, regardless of FVIII at baseline. The decrease in total ABR between the 8-12% and 1-3% arms was greatest in patients with a FVIII of 6 to <12 h (0.7 3.5); a higher number of target joints, that is, at least four target joints, at baseline (0.2 1.6); the presence of arthropathy (0.1 1.7); and those previously treated on-demand (0.3 1.8).

CONCLUSION

These results support the feasibility of targeting elevated FVIII levels using personalized rurioctocog alfa pegol prophylaxis. These benefits may be especially important in patients with a short FVIII and those receiving standard prophylaxis with frequent breakthrough bleeds, arthropathy, and target joints.

REGISTRATION

ClinicalTrials.gov Identifier: NCT02585960; https://clinicaltrials.gov/ct2/show/NCT02585960.