lanadelumab

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Ligands
lanadelumab

GtoPdb Ligand ID: 9094

Synonyms: DX-2930 | lanadelumab-flyo | Takhzyro® | X124-G01

lanadelumab is an approved drug (EMA & FDA (2018))

Comment: Lanadelumab is a fully human monoclonal antibody targeting the serine peptidase kallikrein B1 (KLKB1, a.k.a. plasma kallikrein). It is generated in recombinant Chinese hamster ovary cells.
Annotated peptide sequences for this antibody are available from its IMGT/mAb-DB record. Protein BLAST analysis reveals 100% matches with peptides claimed in patent US8816055 [5].

View interactive charts of activity data across species

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Summary of Clinical Use
Lanadelumab was evaluated in Phase 3 clinical trial in patients with hereditary angioedema (HAE)- see NCT02586805. The EMA granted orphan drug designation in 2015, and the FDA (2017) has designated lanadelumab as a breakthrough therapy for prevention of HAE attacks. In 2018, the EMA and FDA granted lanadelumab (Takhzyro®) full approval as a prophylactic for the prevention of swelling attacks caused by types I and II HAE. It can be prescribed for patients 12 years and older. COVID-19: Elevated levels of bradykinin have been detected in COVID-19 patients, and it is proposed that this might underlie many of the highly debilitating symptoms of the infection [1-2,4]. By inhibiting the plasma kallikrein-bradykinin axis lanadelumab provides an existing therapeutic option with potential to reduce the multi-system effects of bradykinin. SARS-CoV-2 destruction of ACE2 could participate in the loss of regulation of bradykinin levels [3]. Icatibant also acts on this pathway (it antagonises bradykinin signalling via its receptor), and is being tested in COVID-19 patients.

Summary of Clinical Use

Lanadelumab was evaluated in Phase 3 clinical trial in patients with hereditary angioedema (HAE)- see NCT02586805. The EMA granted orphan drug designation in 2015, and the FDA (2017) has designated lanadelumab as a breakthrough therapy for prevention of HAE attacks. In 2018, the EMA and FDA granted lanadelumab (Takhzyro®) full approval as a prophylactic for the prevention of swelling attacks caused by types I and II HAE. It can be prescribed for patients 12 years and older.

COVID-19: Elevated levels of bradykinin have been detected in COVID-19 patients, and it is proposed that this might underlie many of the highly debilitating symptoms of the infection [1-2,4]. By inhibiting the plasma kallikrein-bradykinin axis lanadelumab provides an existing therapeutic option with potential to reduce the multi-system effects of bradykinin. SARS-CoV-2 destruction of ACE2 could participate in the loss of regulation of bradykinin levels [3]. Icatibant also acts on this pathway (it antagonises bradykinin signalling via its receptor), and is being tested in COVID-19 patients.

Mechanism Of Action and Pharmacodynamic Effects
Uncontrolled plasma kallikrein activity leads to excessive generation of bradykinin. Bradykinin is a vasodilator that is believed to be responsible for the localized swelling, inflammation and pain characteristic of HAE. Lanadelumab-induced inhibition of plasma kallikrein is proposed to reduce formation of bradykinin, to bring about an improvement in disease symptoms.

Mechanism Of Action and Pharmacodynamic Effects

Uncontrolled plasma kallikrein activity leads to excessive generation of bradykinin. Bradykinin is a vasodilator that is believed to be responsible for the localized swelling, inflammation and pain characteristic of HAE. Lanadelumab-induced inhibition of plasma kallikrein is proposed to reduce formation of bradykinin, to bring about an improvement in disease symptoms.

Clinical Trials
Clinical Trial ID	Title	Type	Source	Comment	References
NCT02586805	Efficacy and Safety Study of DX-2930 to Prevent Acute Angioedema Attacks in Patients With Type I and Type II HAE	Phase 3 Interventional	Shire
NCT04460105	Lanadelumab in Participants Hospitalized With COVID-19 Pneumonia	Phase 1 Interventional	Takeda
NCT04422509	Lanadelumab for Treatment of COVID-19 Disease	Phase 1/Phase 2 Interventional	Radboud University