Sustained Effectiveness of Lanadelumab in Preventing Hereditary Angioedema Attacks: The ENABLE Study.

BACKGROUND: Lanadelumab has been approved for hereditary angioedema (HAE) long-term prophylaxis since 2018. The Phase 4, prospective ENABLE Study (NCT04130191) evaluated the long-term effectiveness and safety of lanadelumab in clinical practice across Europe and the Middle East. METHODS: Patients with HAE aged ≥ 12 years initiating lanadelumab treatment (300 mg every 2 weeks) per approved product labeling were recruited from Austria, Germany, Israel, Italy, Kuwait, Spain, and Switzerland and followed for up to 36 months (± 30 days). The primary objective was to evaluate lanadelumab effectiveness for HAE attack prevention. Safety and patient-reported health-related quality of life (HRQoL) were also evaluated. RESULTS: Outcomes were analyzed in 138 patients (mean [range] age: 41.0 [14-79] years; 62.3% female; 92.0% HAE-C1INH-Type1), of whom > 60% extended dosing intervals by Month 12. Over a mean ± SD treatment duration of 28.6 ± 9.8 months, mean ± SD patient-reported HAE attack rate decreased from 3.88 ± 3.43 attacks/month pre-lanadelumab to 0.30 ± 0.53 attacks/month (mean decrease, 84% [median 96%]). The incidence-rate ratio was 0.07 (95% CI: 0.06-0.10), reflecting a 93% reduction from modeled pre-lanadelumab rates. Overall, 95/138 patients reported treatment-emergent adverse events (TEAEs); most were unrelated to lanadelumab (82.3%). Of the 17.7% of TEAEs considered treatment-related, injection-site reactions, headache, fatigue, and asthenia occurred in > 1 patient. Before lanadelumab initiation, most patients reported moderate-to-large HRQoL impairments; clinically meaningful improvements were observed 1 month after lanadelumab initiation and sustained throughout the study. CONCLUSIONS: Real-world data from ENABLE demonstrated long-term effectiveness of lanadelumab in patients with HAE aged ≥ 12 years and a safety profile consistent with previous clinical studies.