Lanadelumab

證據等級: L5

預測適應症: 10 個

Lanadelumab: From No Registered Indication (Not Marketed) to C1 Inhibitor Deficiency

One-Sentence Summary

Lanadelumab (DB14597) has no recorded original indication and is currently not marketed in this jurisdiction, so no prior therapeutic use can be extracted from the regulatory data on file. The TxGNN model predicts it may be effective for C1 Inhibitor Deficiency (the molecular basis of hereditary angioedema, HAE), a signal already backed by 22 clinical trials and 20 publications — including a completed pivotal Phase 3 RCT — making this one of the strongest-evidenced predictions in the pipeline.

Quick Overview

Item	Content
Original Indication	Not available — no license records on file (drug not marketed in this jurisdiction)
Predicted New Indication	C1 Inhibitor Deficiency
TxGNN Prediction Score	99.9955% (rank #248 among all predictions)
Evidence Level	L2 (1 completed Phase 3 RCT — HELP Study, NCT02586805 — plus a broad supporting Phase 3/real-world program)
Market Status	✗ Not Marketed
Number of NDAs	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

The original_moa field is a confirmed data gap, but the evidence pack’s own literature record fills part of that gap: PMID 30267321 describes lanadelumab as “a fully human monoclonal antibody that inhibits plasma kallikrein,” acting downstream of mutations in the SERPING1 gene that cause C1 inhibitor deficiency and the resulting uncontrolled bradykinin generation that drives hereditary angioedema (HAE) attacks. PMID 30539362 corroborates this mechanism across preclinical and Phase I data.

This is notable because the predicted indication — C1 inhibitor deficiency — is not a distant repurposing hypothesis but sits directly on the drug’s known pharmacological pathway: plasma kallikrein inhibition is the accepted rationale for treating C1-INH deficiency/HAE. The clinical trial portfolio confirms this is an established, not speculative, use: a completed placebo-controlled Phase 3 trial (HELP Study), a long-term open-label extension (HELP OLE), and regional confirmatory Phase 3 studies in Chinese and Japanese populations, plus real-world registries spanning the US, UK, Argentina, Poland, Romania, Saudi Arabia, South Korea, and China.

In short, the TxGNN signal here largely reflects a mechanistically well-established therapeutic relationship rather than a novel hypothesis — the main gap is administrative (no local license/regulatory filing on record) rather than scientific.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT02586805	Phase 3	Completed	125	HELP Study — pivotal randomized, double-blind, placebo-controlled trial of lanadelumab for long-term prophylaxis against HAE attacks
NCT02741596	Phase 3	Completed	212	HELP Study Extension — open-label long-term safety and efficacy follow-up
NCT04444895	Phase 3	Completed	73	Long-term safety/efficacy in adolescents/adults with non-histaminergic angioedema with normal C1-INH
NCT04070326	Phase 3	Completed	21	SPRING Study — safety, PK/PD in pediatric subjects 2 to <12 years
NCT05460325	Phase 3	Completed	20	Safety, PK, and efficacy in Chinese subjects with HAE
NCT04180163	Phase 3	Completed	12	Efficacy and safety in Japanese subjects with HAE Type I/II
NCT04687137	Phase 3	Completed	12	Japan expanded access program prior to local licensure
NCT04861090	N/A	Completed	207	Retrospective chart review of real-world effectiveness/disease management on long-term prophylaxis
NCT03845400	N/A	Completed	168	EMPOWER Study — observational HAE attack rate before/after lanadelumab initiation (US/Canada)
NCT04130191	N/A	Completed	140	ENABLE Study — 3-year prospective real-world effectiveness

Literature Evidence

PMID	Year	Type	Journal	Key Findings
30480729	2018	RCT	JAMA	Pivotal randomized trial: lanadelumab vs placebo significantly reduces HAE attack frequency
30267321	2018	Review	Drugs	First global approval review; describes plasma kallikrein inhibition mechanism tied to SERPING1/C1-INH deficiency
32187470	2020	Review	New England Journal of Medicine	General review of hereditary angioedema pathophysiology and management
40434599	2025	Network Meta-Analysis	Drugs in R&D	Comparative efficacy/safety of lanadelumab vs other long-term prophylaxis agents (garadacimab, C1INH, berotralstat)
39508959	2024	Systematic Review	Clinical Reviews in Allergy & Immunology	Characterizes breakthrough attacks in patients on long-term prophylaxis, including lanadelumab
39836016	2025	Systematic Review	Journal of Comparative Effectiveness Research	Indirect treatment comparison of lanadelumab vs C1-esterase inhibitor in pediatric HAE
33602658	2021	Review	Journal of Investigational Allergology & Clinical Immunology	Review of current and emerging HAE therapies including kallikrein-kinin pathway inhibition
37898409	2024	Review	Journal of Allergy and Clinical Immunology	Disease burden of C1-inhibitor deficiency HAE with Asia-Pacific regional focus
34287942	2022	Long-term Extension Study	Allergy	HELP OLE Study — long-term effectiveness and safety of lanadelumab in patients ≥12 years
39701274	2025	Observational	Journal of Allergy and Clinical Immunology: In Practice	INTEGRATED multicountry real-world effectiveness study

US Market Information

No license records are on file — Lanadelumab is currently not marketed in this jurisdiction (0 NDAs). External evidence from the clinical trial registry indicates approved status in other markets (e.g., “Takhzyro is an approved treatment for hereditary angioedema (HAE) in South Korea” per NCT07445087, and Chinese health authority approval per NCT06346899), but no local authorization data is available to populate this table.

Safety Considerations

Please refer to the package insert for safety information.

(Note: taiwan_regulatory and safety data gaps are flagged as Blocking in the source evidence pack — TFDA label warnings/contraindications and DDI data could not be retrieved.)

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: The evidence level (L2) understates the true strength of support — a completed placebo-controlled Phase 3 RCT (HELP Study) is backed by an extensive Phase 3 program across multiple populations (Chinese, Japanese, pediatric) plus large real-world registries, and the drug already appears to hold regulatory approval for this exact indication in other markets. However, a Blocking data gap (DG001: no local TFDA label/warnings data) means the drug cannot yet clear an initial safety review (S1) in this jurisdiction, so a full “Go” is not yet warranted.

To proceed, the following is needed:

TFDA (or equivalent local regulator) label data — warnings, precautions, and contraindications (DG001, Blocking)
Confirmed mechanism-of-action documentation from DrugBank or manufacturer labeling (DG002)
Drug-drug interaction (DDI) profile, currently returning no results
Confirmation of local regulatory filing/registration pathway, given the drug is not currently marketed here
Disclaimer

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