Lanadelumab

證據等級: L5

預測適應症: 10 個

Lanadelumab: From Hereditary Angioedema to C1 Inhibitor Deficiency

One-Sentence Summary

Lanadelumab (Takhzyro®) is a monoclonal antibody that inhibits plasma kallikrein; the clinical trial records in this evidence pack show it is an already-approved prophylactic treatment for hereditary angioedema (HAE) in multiple countries (e.g. Japan, China, South Korea), though no formal indication/MOA record for this drug exists in the current evidence pack and it currently holds no marketing authorisation in Denmark. The TxGNN model’s top prediction, C1 Inhibitor Deficiency, is the pathophysiological name for Type I/II HAE — i.e., essentially the same disease Lanadelumab is already used for elsewhere. This is supported by 22 clinical trials and 20 publications, but should be read as a confirmation of an existing global indication rather than a novel repurposing signal.

Quick Overview

Item	Content
Original Indication	Hereditary Angioedema (HAE) — inferred from clinical trial evidence in this pack; no formal indication/MOA record is on file for this drug
Predicted New Indication	C1 Inhibitor Deficiency (clinically synonymous with HAE Type I/II)
TxGNN Prediction Score	99.996%
Evidence Level	L2 (1 completed Phase 3 RCT: HELP Study, NCT02586805)
Denmark Market Status	Not marketed
Number of Marketing Authorisations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism-of-action data is not formally on file for this drug in the evidence pack (original_moa: Data Gap). However, the literature evidence collected alongside the prediction (PMID 30267321) describes Lanadelumab as “a fully human monoclonal antibody that inhibits plasma kallikrein,” developed to prevent hereditary angioedema (HAE) attacks caused by mutations in SERPING1 leading to C1 inhibitor deficiency or dysfunction, which results in uncontrolled plasma kallikrein activity and excessive bradykinin production.

Importantly, “C1 Inhibitor Deficiency” — the TxGNN top prediction — is not a distinct new disease relative to HAE; it is the underlying biochemical classification of HAE Type I/II, the condition Lanadelumab was originally developed and is already approved for in multiple jurisdictions (trial records in this pack reference approval status in Japan, China, and South Korea). This means the model has essentially re-identified the drug’s known indication rather than surfaced a genuine repurposing candidate. The predictive score is very high (99.996%) precisely because the drug–disease association is already well established in the underlying knowledge graph.

Three other TxGNN predictions in this evidence pack (serpinopathy with toxic serpin polymerization, pancreatitis, pseudo-von Willebrand disease, primary release disorder of platelets) scored highly but have no supporting clinical trials or literature and were scored L5/Hold — these are not discussed further here as they lack any evidentiary basis.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT02586805	Phase 3	Completed	125	HELP Study — randomized, double-blind, placebo-controlled trial confirming efficacy/safety of Lanadelumab (DX-2930) for long-term HAE prophylaxis
NCT02741596	Phase 3	Completed	212	HELP Study Extension — open-label long-term safety and efficacy follow-up
NCT04070326	Phase 3	Completed	21	SPRING Study — safety, PK/PD in pediatric HAE patients 2 to <12 years
NCT04180163	Phase 3	Completed	12	Efficacy and safety in Japanese HAE Type I/II patients
NCT05460325	Phase 3	Completed	20	Safety, PK and efficacy in Chinese HAE patients over 26 weeks
NCT04444895	Phase 3	Completed	73	Long-term safety/efficacy in non-histaminergic angioedema with normal C1-INH
NCT04130191	N/A	Completed	140	ENABLE — 3-year real-world effectiveness study
NCT03845400	N/A	Completed	168	EMPOWER — observational HAE attack-rate study, US/Canada
NCT02093923	Phase 1	Completed	38	Multiple ascending dose safety/tolerability/PK study in HAE subjects
NCT01923207	Phase 1	Completed	32	First-in-human single ascending dose safety/tolerability study in healthy subjects

No EudraCT identifiers were present in the evidence pack.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
30480729	2018	RCT	JAMA	Lanadelumab vs. placebo significantly reduces HAE attack rate (HELP Study primary publication)
40434599	2025	Network Meta-Analysis	Drugs in R&D	Comparative efficacy/safety of Lanadelumab vs. garadacimab, C1-INH, berotralstat for HAE prophylaxis
39508959	2024	Systematic Review	Clinical Reviews in Allergy & Immunology	Characterizes breakthrough attacks in HAE patients on long-term prophylaxis
39836016	2025	Indirect Treatment Comparison	J Comp Eff Res	Compares Lanadelumab vs. C1-INH in pediatric HAE (<12 years)
34287942	2022	Open-label Extension	Allergy	HELP OLE Study — long-term effectiveness and safety confirmed
30267321	2018	Review	Drugs	“Lanadelumab: First Global Approval” — MOA and development summary
32187470	2020	Review	NEJM	General review of hereditary angioedema pathophysiology and treatment
30539362	2019	Review	BioDrugs	Preclinical and Phase I data review for Lanadelumab in C1-INH deficiency
37898409	2024	Review	J Allergy Clin Immunol	Disease burden of HAE due to C1-inhibitor deficiency in Asia-Pacific
39701274	2025	Observational	J Allergy Clin Immunol Pract	INTEGRATED multicountry real-world effectiveness study

Denmark Market Information

Lanadelumab currently holds no marketing authorisation in Denmark (0 licences on file; market status: not marketed). No national (Laegemiddelstyrelsen) or centralised (EMA) authorisation records are available in this evidence pack.

Safety Considerations

Please refer to the approved Summary of Product Characteristics (SmPC) for safety information.

Conclusion and Next Steps

Decision: Hold

Rationale:

A blocking data gap exists (DG001: no TFDA/SmPC warnings or contraindications on file), which prevents completion of the initial safety screening (S1) required before any recommendation to proceed. This holds even though the underlying indication is not novel — Lanadelumab is already an approved HAE therapy elsewhere, supported by one completed placebo-controlled Phase 3 RCT (L2) and substantial real-world evidence.

To proceed, the following is needed:

Official SmPC / product label with warnings, precautions, and contraindications (source: TFDA or equivalent regulator)
Formal mechanism-of-action (MOA) record from DrugBank or manufacturer labeling
Drug-drug interaction (DDI) data (current query returned no results)
If Danish market entry is being considered: a formal marketing authorisation application, since no licence currently exists in Denmark
Clarification that “C1 Inhibitor Deficiency” reflects the drug’s existing approved indication rather than a new repurposing target, to avoid mischaracterizing this as a novel finding
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.