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Publications

Journal Article Ppublish

PubMed: 42563375 DOI: 10.1002/clt2.70190

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

Clin Transl Allergy 16(8):e70190

Authors: 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-Saguer

Affiliations

  • Operative Unit of Medicine, Angioedema Center, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.
  • Dipartimento di Scienze Biomediche per la Salute, University of Milan, Milan, Italy.
  • Luzerner Kantonsspital, Lucerne and University of Berne, Berne, Switzerland.
  • Charité-Universitätsmedizin Berlin (corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin), Berlin, Germany.
  • Fraunhofer Institute for Translational Medicine and Pharmacology ITMP IA, Berlin, Germany.
  • University of Lübeck, Lübeck, Germany.
  • University Hospital of Padua, Padua, Italy.
  • University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
  • Allergology Department, Hospital Universitari de Bellvitge, Institut de Recerca IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
  • Bnai Zion Medical Centre, Technion Faculty of Medicine, Haifa, Israel.
  • Department of Dermatology, Medical University of Vienna, Vienna, Austria.
  • Ulm University Medical Center, Ulm, Germany.
  • Microbiology Department, College of Medicine, Kuwait University, Kuwait City, Kuwait.
  • Takeda Pharmaceuticals International AG, Zurich, Switzerland.
  • Takeda Development Center Americas Inc. Lexington, Massachusetts, USA.
  • HZRM Hemophilia Center Rhine Main, Frankfurt/Main, Germany.

Abstract

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.

MeSH

Quality Of Life, Safety, Incidence, Angioedemas, Hereditary, Aged, Therapeutics, Angioedema