OBJECTIVES: Novel therapies in hemophilia aim to deliver quality-of-life benefits beyond reductions in bleeding. The extent of quality-of-life benefits may vary across different therapies. Head-to-head data from valoctocogene roxaparvovec with emicizumab are not available, thus requiring an indirect comparison. This study compares the EQ-5D utilities of valoctocogene roxaparvovec using data from the GENEr8-1 clinical trial, with calculated utilities of emicizumab from HAVEN-3 trial Arm D.

METHODS: GENEr8-1 utilities were calculated using individual participant data with the UK crosswalk and reweighted based on a published matching-adjusted indirect comparison (MAIC). This MAIC balanced patient baseline characteristics to match those of HAVEN-3 Group D. Since HAVEN-3 Group D utilities are not reported, we used public data from the HAVEN-3 trial and linear programming with assumptions to estimate HAVEN-3 Arm D utilities (previously reported methodology). We compared utilities before and after reweighting between the two treatments.

RESULTS: GENEr8-1 mITT (N=132 patients) unweighted mean utilities were 0.766 at baseline, increasing to 0.800 at 26 weeks, and 0.812 at year 1. After re-weighting, the values were 0.725, 0.773 and 0.791 for baseline, weeks 26, and 52, respectively. Corresponding utilities for emicizumab were calculated as 0.79 for baseline, 0.82 for week 25, and 0.82 for week 49. After the MAIC, the improvement in utility at week 52 was 0.07 for valoctocogene roxaparvovec and 0.03 for emicizumab, with a greater gain for valoctocogene roxaparvovec of 0.04 (0.02 before MAIC).

CONCLUSIONS: This study demonstrates the importance of reweighting utility outcomes via MAIC. After accounting for differences in patient characteristics and incorporating linear programming assumptions, valoctocogene roxaparvovec appears to show a greater utility increase than emicizumab. These results can inform treatment-arm specific utilities in cost-effectiveness modelling, capturing utility gain beyond reductions in bleeds.