Sustained Effectiveness of Lanadelumab in Preventing Hereditary Angioedema Attacks: The ENABLE Study
Andrea Zanichelli, Walter A. Wuillemin, Markus Magerl, Andreas Recke, Mauro Cancian, Emel Aygören‐Pürsün, Ramón Lleonart Bellfill, Aharon Kessel, Tamar Kinaciyan, Robin Lochbaum, Mona Al‐Ahmad, Irmgard Andresen, Maureen Watt, Natalie Khutoryansky, Daniel N. Castaner, Inmaculada Martinez‐SaguerABSTRACT
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.