The Effectiveness and Value of Lanadelumab and C1 Esterase Inhibitors for Prophylaxis of Hereditary Angioedema Attacks

Abstract

■■ Summary of Findings Clinical Effectiveness We evaluated the literature supporting the clinical effectiveness and safety of Cinryze, Haegarda, and Takhyzro for long-term prophylaxis in patients with HAE 1/2 compared with on-demand treatment only. Due to differences in trial entry criteria (particularly age and baseline attack rates) and study design, as well as small study populations, we did not perform a quantitative indirect comparison of the 3 drugs through network meta-analysis. As such, our review evaluated the comparative findings from the clinical trials of each agent. Complete details on ICER's systematic literature search and protocol, including search strategy and inclusion and exclusion criteria, are included in the final evidence report, which is available on ICER's website. 8 Cinryze. The pivotal trial for Cinryze was a crossover ran-domized controlled trial (RCT) of 22 HAE 1/2 patients aged 6 years and older, who had a history of 2 or more attacks per month. Patients were randomized to receive either 1,000 IU of Cinryze or placebo intravenously (every 3-4 days) for two 12-week treatment periods. 9 Patients in both arms of the trials received on-demand treatment for attacks as needed. The primary outcome was patient-reported HAE attacks. Compared with the placebo arm, prophylactic treatment with Cinryze significantly reduced the frequency of HAE attacks (estimated mean attack rate per month: 4.24 vs. 2.09; P < 0.001). 9 In addition , Cinryze was also shown to significantly reduce the severity and duration of HAE attacks and use of rescue medication when compared with placebo. 9 Furthermore, Cinryze appeared to improve health-related quality of life based on increased SF-36 scores in the treatment group, although statistical significance was not reported. 9 Another randomized crossover study, conducted in an exclusively pediatric population (N = 12), also found that long-term prophylaxis with Cinryze significantly reduced the mean HAE arrack rate by 71%-85% when compared with placebo. 10 In addition, data from an open label extension study conducted over 2.6 years (N = 146) showed a sustained reduction in the monthly rate of HAE attacks. 11