D2.331 - Lanadelumab safety and efficacy in patients aged ≥12 with hereditary angioedema (HAE) in China for long-term prophylaxis (LTP): An open-label, multicenter study

HAE is a rare, debilitating genetic disease that manifests in unpredictable, recurrent, painful, and potentially fatal swelling attacks. Lanadelumab is a human monoclonal antibody inhibitor of plasma kallikrein approved for HAE LTP in many countries, including the US, EU, Japan, and China. Here, we report its safety and efficacy in Chinese patients in the post-approval commitment study.

This open-label, phase 3 study included patients in China aged ≥12 years with HAE Type I/II (NCT05460325). Once screened (≤4 weeks), patients entered a 4–8-week pre-lanadelumab (run-in) period to determine baseline attack rate; adults using LTPs prior to enrollment were to enter a 14-day washout period. Eligible patients with ≥1 HAE attack per 4 weeks (/4w) in the run-in period received 14 doses of subcutaneous lanadelumab 300 mg biweekly from Days 0–182 and with a 4-week follow-up thereafter. The primary objective was evaluation of safety, including treatment-emergent adverse events (TEAEs). Secondary objectives included changes in monthly HAE attack rates during Days 0–182 vs run-in.

Overall, 20 patients were enrolled and all completed the study (median age: 38 years [<18 years: n=1]; 7 male). 85% of patients had no prior LTP use. Fifteen (75%) patients reported ≥1 TEAE (non‑HAE attack-related) during the study, most commonly COVID-19 (50%). In total, 9 (45%) patients reported treatment-related TEAEs, most frequently injection site pain (20%) and swelling (15%). Injection site reactions occurred in 25% of patients. No TEAEs were fatal, led to treatment discontinuation, or were of special interest. Two serious TEAEs were reported, both in the same patient and unrelated to treatment. Mean±standard deviation (SD) attack rate decreased by 99.1% during Days 0–182 vs run-in (0.04±0.14 vs 2.50±1.44 attacks/4w); moderate-to-severe attacks and those requiring acute treatment decreased by 99.7% (0.01±0.03 vs 1.22±1.15 attacks/4w) and 99.6% (0.01±0.03 vs 0.74±0.97 attacks/4w) from run-in, respectively. During Days 0–182, 95% of patients achieved ≥90% reduction in the normalized number of attacks (NNA)/4w from run-in, all achieved NNA/4w<1. Eighteen (90%) patients were attack-free from Days 0–182, 2 patients experienced a total of 5 HAE attacks (4 mild, 1 moderate). 

These findings in Chinese patients with HAE are consistent with the favorable lanadelumab safety and efficacy profile reported in populations from other regions.