Long-term efficacy and safety of subcutaneous C1-inhibitor in women with hereditary angioedema: subgroup analysis from an open-label extension of a phase 3 trial.

BACKGROUND

Women with hereditary angioedema due to C1-inhibitor deficiency (HAE-C1INH) experience more frequent and severe angioedema attacks compared with men. Fluctuations in female sex hormones can influence HAE attack frequency and severity. Subcutaneous C1-INH (C1-INH [SC]) is indicated as routine prophylaxis to prevent HAE attacks. In this post hoc subgroup analysis, we evaluated the efficacy and safety of C1-INH (SC) in female subjects with HAE-C1INH enrolled in an open-label extension of the pivotal phase III COMPACT trial.

METHODS

In this multicenter, randomized, parallel-arm trial, eligible subjects (age ≥ 6 years with ≥ 4 attacks over 2 consecutive months) received C1-INH (SC) 40 IU/kg or 60 IU/kg twice weekly for 52 to 140 weeks. Analyses of efficacy endpoints were performed for all female subjects and those of childbearing age (age ≥ 15 to ≤ 45 years), including subjects who became pregnant during the evaluation period.

RESULTS

Overall, 91% (69/76) of female subjects were classified as responders (≥ 50% reduction in HAE attacks relative to the pre-study period); 82% experienced < 1 attack/4 weeks. The median number of attacks/month was 0.10, with 96% median reduction in attacks relative to the pre-study period. Results were similar in the subgroup of subjects of childbearing age. Four women who became pregnant during the trial and were exposed to C1-INH (SC) during the first trimester delivered healthy babies with no congenital abnormalities.

CONCLUSIONS

C1-INH (SC) prophylaxis was safe and effective in women with HAE-C1INH, including those of childbearing age. Four women exposed to C1-INH (SC) during the first trimester had uneventful pregnancies and delivered healthy babies.

Informations de copyright

© The Author(s) 2020.

Déclaration de conflit d'intérêts

Competing interestsD. Levy has served on the speaker’s bureau, as a consultant, on a steering committee, and as a clinical investigator for CSL Behring; consultant for BioCryst; and speaker for Takeda. H. Farkas received institutional support for a clinical trial for this study from CSL Behring; advisory board/consultancy fees and/or speaker’s honoraria from BioCryst, CSL Behring, Shire, and Sobi (Swedish Orphan Biovitrum); and travel support from CSL Behring. M. Riedl reports grant support from CSL Behring during the conduct of the study and has received research grants from BioCryst, CSL Behring, Dyax, Ionis Pharmaceuticals, Pharming Technologies, and Shire; has served as a consultant and/or speaker for Adverum Biotechnologies, Alnylam Pharmaceuticals, Arrowhead Pharmaceuticals, BioCryst, CSL Behring, Dyax, Global Blood Therapeutics, Ionis Pharmaceuticals, KalVista Pharmaceuticals, Pharming Technologies, Salix Pharmaceuticals, and Shire; and is an uncompensated advisory board member for the US Hereditary Angioedema Association, outside the submitted work. F. Hsu reports serving as a consultant for BioCryst; serving as a speaker for CSL Behring, Pharming Technologies BV, and Takeda Pharmaceutical Company Ltd; and performing contracted research for Hoffman-La Roche. J.P. Brooks declares that he has no competing interests. M. Cicardi received grants from Shire and personal fees from Alnylam, BioCryst, CSL Behring, Dyax, KalVista, Pharming Technologies, Shire, Sobi (Swedish Orphan Biovitrum), and ViroPharma. H. Feuersenger and I. Pragst are employees of CSL Behring. A. Reshef reports grant support from CSL Behring during the conduct of the study and has received grant support from Pharming.