Lanadelumab

Evidence Level: L5

Predicted Indications: 10

Lanadelumab
Lanadelumab: From Hereditary Angioedema Prophylaxis to C1 Inhibitor Deficiency

## Pharmacist Assessment Report

Lanadelumab: From Hereditary Angioedema Prophylaxis to C1 Inhibitor Deficiency

One-Sentence Summary

Lanadelumab (Takhzyro) is a monoclonal antibody that blocks plasma kallikrein and is already marketed to prevent hereditary angioedema (HAE) attacks. The TxGNN model predicts it may be effective for C1 inhibitor deficiency, supported by 22 clinical trials and 20 publications. This prediction largely restates the approved use, because HAE types I and II are C1 inhibitor deficiency. The real repurposing question is the acquired form of C1-INH deficiency, which rests only on small case series.

Quick Overview

Item	Content
Original Indication	Not recorded in the US license entries; the drug is marketed for HAE prophylaxis
Predicted New Indication	C1 inhibitor deficiency
TxGNN Prediction Score	99.996%
Evidence Level	L1 as scored in the Evidence Pack (strictly L2, since only the HELP trial is a randomized Phase 3)
US Market Status	✓ Marketed
Number of NDAs	3 listings (all under BLA761090)
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Detailed mechanism data is missing from the record, but the mechanism is well understood. Lanadelumab is a fully human monoclonal antibody that inhibits plasma kallikrein. In C1 inhibitor deficiency, the body lacks enough functional C1-INH, so plasma kallikrein goes unchecked. This drives excess bradykinin, a vasodilator that causes the swelling attacks. Blocking kallikrein directly targets this pathway.

The predicted indication and the approved use overlap almost completely. HAE type I/II is C1-INH deficiency, and the pivotal trials studied it. The prediction is therefore best read as a data artifact (the record lists no original indications) rather than true repurposing. The genuinely new use is acquired C1-INH deficiency. Two case series (2021 and 2023) report efficacy there, but no prospective trial exists.

Clinical Trial Evidence

Shown are the 10 most relevant of 22 trials.

Trial Number	Phase	Status	Enrollment	Key Findings
NCT02586805	Phase 3	Completed	125	HELP Study: randomized, double-blind, placebo-controlled trial of long-term prevention of attacks in type I/II HAE
NCT02741596	Phase 3	Completed	212	HELP Study Extension: open-label long-term safety and efficacy
NCT04070326	Phase 3	Completed	21	SPRING: open-label safety, PK and PD in children aged 2 to <12
NCT05460325	Phase 3	Completed	20	Open-label, 26-week safety, PK and efficacy study in Chinese HAE patients
NCT04180163	Phase 3	Completed	12	Open-label efficacy and safety in Japanese HAE patients
NCT04687137	Phase 3	Completed	12	Japan expanded access program for HAE type I/II
NCT04444895	Phase 3	Completed	73	Long-term safety and efficacy in non-histaminergic angioedema with normal C1-INH, a different condition from C1-INH deficiency
NCT04130191	N/A	Completed	140	ENABLE: 3-year real-world study comparing attack numbers before and after starting lanadelumab
NCT03845400	N/A	Completed	168	EMPOWER: observational study of HAE attack rates before and after lanadelumab in the US and Canada
NCT06346899	N/A	Completed	115	Real-world effectiveness and safety of lanadelumab and icatibant in China

Literature Evidence

Shown are the 10 most relevant of 20 publications.

PMID	Year	Type	Journal	Key Findings
30480729	2018	RCT	JAMA	Lanadelumab versus placebo for preventing HAE attacks (HELP trial)
34287942	2022	Open-label extension of Phase 3 RCT	Allergy	HELP OLE: long-term effectiveness and safety in patients aged 12 and older with HAE 1/2
39701274	2025	Observational	J Allergy Clin Immunol Pract	INTEGRATED: multicountry real-world effectiveness in HAE
39508959	2024	Systematic review	Clin Rev Allergy Immunol	Breakthrough attacks in type I/II HAE patients on long-term prophylaxis
40434599	2025	Network meta-analysis	Drugs R D	Indirect comparison of long-term prophylaxis options (garadacimab, lanadelumab, SC C1-INH, berotralstat)
39836016	2025	Indirect treatment comparison	J Comp Eff Res	Lanadelumab versus a C1-esterase inhibitor in children under 12 with HAE
33556593	2021	Case series	J Allergy Clin Immunol Pract	Efficacy of lanadelumab in acquired angioedema with C1-inhibitor deficiency
36379410	2023	Case series	J Allergy Clin Immunol Pract	Efficacy of lanadelumab in angioedema due to acquired C1 inhibitor deficiency
32187470	2020	Review	N Engl J Med	Overview of hereditary angioedema
30539362	2019	Review	BioDrugs	Preclinical and Phase I studies of lanadelumab for HAE with C1-INH deficiency

US Market Information

Authorization Number	Product Name	Dosage Form	Approved Indication
BLA761090	TAKHZYRO (Takeda Pharmaceuticals America, Inc.)	Solution	—
BLA761090	TAKHZYRO (Takeda Pharmaceuticals America, Inc.)	Solution	—
BLA761090	TAKHZYRO (Takeda Pharmaceuticals America, Inc.)	Injection, solution	—

The three rows are separate listings under a single BLA. The record contains no indication text.

Safety Considerations

Please refer to the package insert for safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: The mechanism is clear, and a completed randomized Phase 3 trial (HELP) plus several Phase 3 open-label studies and real-world cohorts support use in C1-INH-deficient HAE, which is already marketed. The other nine predictions (serpinopathy, pancreatitis, platelet and myopathy disorders and others) have no trials, no literature and no plausible mechanism. They stay at Hold.

To proceed, the following is needed:

The current US package insert, to confirm the labeled indication and to fill in warnings and contraindications
DrugBank mechanism-of-action data to complete the record
A prospective study before any use in acquired C1-INH deficiency, which is off-label and supported only by small case series
Disclaimer

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