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Identification
- Summary
Lanadelumab is a monoclonal antibody targeted against kallikrein which is used to treat attacks of hereditary angioedema.
- Brand Names
- Takhzyro
- Generic Name
- Lanadelumab
- DrugBank Accession Number
- DB14597
- Background
Lanadelumab, also known as DX-2930, is a human IgG1 monoclonal antibody designed for subcutaneous self-injection.6 It is a fully human immunoglobulin, k-light-chain made in recombinant Chinese Hamster Ovary cells.5 It has been granted priority review, breakthrough therapy, and orphan drug designations for rare diseases based on the results of clinical trials.1 Lanadelumab was approved for use in patients with hereditary angioedema by the FDA in August 2018,5 followed by Health Canada in October 201812 and the EMA in November 2018.11
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Structure
- Protein Chemical Formula
- C6468H10016N1728O2012S47
- Protein Average Weight
- 146000.0 Da
- Sequences
>Heavy chain EVQLLESGGGLVQPGGSLRLSCAASGFTFSHYIMMWVRQAPGKGLEWVSGIYSSGGITVY ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAYRRIGVPRRDEFDIWGQGTMVTV SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELL GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
>Light chain DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYKASTLESGVPS RFSGSGSGTEFTLTISSLQPDDFATYYCQQYNTYWTFGQGTKVEIKRTVAAPSVFIFPPS DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA FormatReferences:
- Health Canada Approved Drug Products: Takhzyro (lanadelumab) solution for subcutaneous injection [Link]
- Synonyms
- Lanadelumab
- Lanadelumab-flyo
- External IDs
- DX-2930
Pharmacology
- Indication
Lanadelumab is indicated for prophylaxis to prevent attacks in adult and pediatric patients aged 2 years and older with hereditary angioedema.9,11 In Canada, it is indicated for use only in adults and adolescents.12
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Prophylaxis of Hereditary angioedema attack •••••••••••• ••••••••• Prophylaxis of Hereditary angioedema attack •••••••••••• ••••••••• Prophylaxis of Hereditary angioedema attack •••••••••••• ••••••••• ••••••••• Prophylaxis of Hereditary angioedema attack •••••••••••• •••••• ••••••••• ••••••••• Prevention of Recurrent angiodema •••••••••••• ••••••••• - Contraindications & Blackbox Warnings
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In phase 1 studies, the level of kininogen, the substrate of kallikrein, was studied as a marker of kallikrein activity. In patients with C1 deficiency, the level of cleaved kininogen is 4-fold higher when compared with C1-normal individuals. When lanadelumab was administered, the levels of cleaved kininogen were significantly reduced with a dose of 300 and 400 mg of lanadelumab with a maximum reduction at day 22 corresponding with time for maximum concentration. This maximum reduction corresponded with the normal levels of cleaved kininogen. Similarly, the decreases of cleaved kininogen corresponded with reductions in the levels of the activated factor XII.2
Clinically, the attacks of angioedema completely vanished in the patients receiving a dose of 300 mg of lanadelumab. In other doses such as 400 mg and combo 300/400 mg the attack reduction reached 90%.2 In phase 3 clinical trials, lanadelumab showed an attack rate reduction of over 70% for all studied regimens.1
- Mechanism of action
Hereditary angioedema (HEA) is an autosomal dominant disorder resulting from the presence of C1 deficiency. This condition manifests as attacks of subcutaneous or submucosal edema in the face, larynx, GI tract, limbs or genitalia, with laryngeal edema being the most serious due to the potential to compromise the airways. Attacks may be accompanied by pain and considerable dysfunction.4
Lanadelumab is a plasma kallikrein inhibitor. This enzyme works by cleaving high molecular weight kininogen to generate the pro-inflammatory peptide bradykinin, a potent vasodilator. Because the activity of plasma kallikrein is regulated by C1 esterase inhibitor, patients deficient in C1 esterase inhibitor may be at risk of excessive production of bradykinin leading to serious angioedema.3 Lanadelumab occludes the proteolytic active site of plasma kallikrein, preventing the cleavage of kininogen to bradykinin. It is a selective inhibitor and does not bind to prekallikrein or inhibit other serine proteases.4
Target Actions Organism APlasma kallikrein inhibitorregulatorHumans - Absorption
Drug levels of lanadelumab are dose-dependent and the maximum plasma concentration increases correspondingly with increasing dosage. The Cmax and AUC ranged from 3800 - 45000 ng/ml and 64000 - 762000 ng.day/ml, respectively, across a dosing range of 30 to 400 mg. A sustained quantifiable drug concentration was observed through day 120.2 The bioavailability of lanadelumab is approximately 66% with a time to reach peak drug concentration of approximately 7 days.9,4
- Volume of distribution
The apparent volume of distribution of lanadelumab is approximately 14 - 16 L depending on the dose administered.9
- Protein binding
Not Available
- Metabolism
As with other therapeutic proteins, the degradation of lanadelumab likely occurs via catabolism to smaller peptides and amino acids.
- Route of elimination
Not Available
- Half-life
Lanadelumab has a half-life of approximately 2 weeks after subcutaneous administration.9
- Clearance
The apparent clearance of lanadelumab ranges from 0.667 to 0.809 L/day depending on the administered dose.9
- Adverse Effects
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No significant toxicities related to the administration of lanadelumab have been reported.4
Studies regarding the carcinogenic potential or overdosage effect have not been performed. Published literature supports bradykinin, which is elevated in HAE, as a pro-tumorigenic molecule. However, the malignancy risk in humans from an antibody that inhibits plasma kallikrein activity, such as lanadelumab-flyo, which lowers bradykinin levels, is currently unknown.9 There are no available data on lanadelumab use in pregnant women to inform of any drug-associated risks. Monoclonal antibodies such as lanadelumab-flyo are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. An enhanced pre-and postnatal development (ePPND) study conducted in pregnant monkeys at doses resulting in exposures of up to 33 times the exposure achieved (on an AUC basis) at the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus.9
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Lanadelumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Lanadelumab. Aducanumab The risk or severity of adverse effects can be increased when Aducanumab is combined with Lanadelumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Lanadelumab. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Lanadelumab. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Takhzyro Injection, solution 300 mg Subcutaneous Takeda Pharmaceuticals International Ag Ireland Branch 2021-01-28 Not applicable EU 
Takhzyro Solution 150 mg/1mL Subcutaneous Takeda Pharma A/S 2023-02-03 Not applicable US 
Takhzyro Solution 300 mg / 2 mL Subcutaneous Takeda Italia S.P.A. 2018-10-31 Not applicable Canada 
Takhzyro Injection, solution 150 mg Subcutaneous Takeda Pharmaceuticals International Ag Ireland Branch 2023-11-28 Not applicable EU Takhzyro Injection, solution 300 mg Subcutaneous Takeda Pharmaceuticals International Ag Ireland Branch 2021-01-28 Not applicable EU
Categories
- ATC Codes
- B06AC05 — Lanadelumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Blood and Blood Forming Organs
- Blood Proteins
- Drugs Used in Hereditary Angioedema
- Globulins
- Immunoglobulins
- Immunoproteins
- Kallikrein Inhibitors
- Plasma Kallikrein Inhibitor
- Proteins
- Serum Globulins
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans
Chemical Identifiers
- UNII
- 2372V1TKXK
- CAS number
- 1426055-14-2
References
- General References
- Kaplon H, Reichert JM: Antibodies to watch in 2018. MAbs. 2018 Feb/Mar;10(2):183-203. doi: 10.1080/19420862.2018.1415671. Epub 2018 Jan 16. [Article]
- Banerji A, Busse P, Shennak M, Lumry W, Davis-Lorton M, Wedner HJ, Jacobs J, Baker J, Bernstein JA, Lockey R, Li HH, Craig T, Cicardi M, Riedl M, Al-Ghazawi A, Soo C, Iarrobino R, Sexton DJ, TenHoor C, Kenniston JA, Faucette R, Still JG, Kushner H, Mensah R, Stevens C, Biedenkapp JC, Chyung Y, Adelman B: Inhibiting Plasma Kallikrein for Hereditary Angioedema Prophylaxis. N Engl J Med. 2017 Feb 23;376(8):717-728. doi: 10.1056/NEJMoa1605767. [Article]
- Reichert JM: Antibodies to watch in 2017. MAbs. 2017 Feb/Mar;9(2):167-181. doi: 10.1080/19420862.2016.1269580. Epub 2016 Dec 14. [Article]
- Chyung Y, Vince B, Iarrobino R, Sexton D, Kenniston J, Faucette R, TenHoor C, Stolz LE, Stevens C, Biedenkapp J, Adelman B: A phase 1 study investigating DX-2930 in healthy subjects. Ann Allergy Asthma Immunol. 2014 Oct;113(4):460-6.e2. doi: 10.1016/j.anai.2014.05.028. Epub 2014 Jun 26. [Article]
- FDA news [Link]
- Globalnews [Link]
- NIH [Link]
- FDA Approved Drug Products: TAKHZYRO (lanadelumab-flyo) injection [Link]
- FDA Approved Drug Products: TAKHZYRO® (lanadelumab-flyo) injection, for subcutaneous use (February 2023) [Link]
- EMA Summary of Product Characteristics: Takhzyro (lanadelumab) solution for subcutaneous administration [Link]
- EMA EPAR: Takhzyro (lanadelumab) [Link]
- Health Canada Approved Drug Products: Takhzyro (lanadelumab) solution for subcutaneous injection [Link]
- WHO sequence of lanadelumab [File]
- External Links
- 2055640
- Wikipedia
- Lanadelumab
- FDA label
- Download (73.1 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available No Longer Available Not Available Angioedema / Hereditary Angioedema (HAE) 1 somestatus stop reason just information to hide Not Available Recruiting Not Available Hereditary Angioedema (HAE) 1 somestatus stop reason just information to hide 3 Completed Prevention Coronavirus Disease 2019 (COVID‑19) / Hereditary Angioedema (HAE) 1 somestatus stop reason just information to hide 3 Completed Prevention Hereditary Angioedema (HAE) 2 somestatus stop reason just information to hide 3 Completed Treatment Angioedema 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Parenteral; Subcutaneous 300 MG Injection, solution Subcutaneous 150 mg Injection, solution Subcutaneous 300 mg Injection, solution Subcutaneous 300 mg/2mL Solution Subcutaneous 150 mg/1mL Solution Subcutaneous 300 mg/2mL Solution Subcutaneous 300 mg / 2 mL Injection, solution 300 mg/2ml - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 80-90 ºC (based on IgG properties) McConnell A., et al. (2014). MAbs. Sep-Oct; 6 (5); 1274-1282 boiling point (°C) Fab and Fc domains denaturates at 60 and 70 ºC respectively Arnoldus W. et al. (2000). Biophysical Journal. Vol 78. 394-404 water solubility 50 mg/ml Human IgG purified. Product Information isoelectric point 6.1-8.5 Agrisera Information about IgG antibodies.
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- InhibitorRegulator
- General Function
- Participates in the surface-dependent activation of blood coagulation. Activates, in a reciprocal reaction, coagulation factor XII/F12 after binding to negatively charged surfaces. Releases bradykinin from HMW kininogen and may also play a role in the renin-angiotensin system by converting prorenin into renin
- Specific Function
- serine-type endopeptidase activity
- Gene Name
- KLKB1
- Uniprot ID
- P03952
- Uniprot Name
- Plasma kallikrein
- Molecular Weight
- 71342.175 Da
References
- Reichert JM: Antibodies to watch in 2017. MAbs. 2017 Feb/Mar;9(2):167-181. doi: 10.1080/19420862.2016.1269580. Epub 2016 Dec 14. [Article]
- Riedl MA, Bernstein JA, Craig T, Banerji A, Magerl M, Cicardi M, Longhurst HJ, Shennak MM, Yang WH, Schranz J, Baptista J, Busse PJ: An open-label study to evaluate the long-term safety and efficacy of lanadelumab for prevention of attacks in hereditary angioedema: design of the HELP study extension. Clin Transl Allergy. 2017 Oct 6;7:36. doi: 10.1186/s13601-017-0172-9. eCollection 2017. [Article]
- Banerji A, Busse P, Shennak M, Lumry W, Davis-Lorton M, Wedner HJ, Jacobs J, Baker J, Bernstein JA, Lockey R, Li HH, Craig T, Cicardi M, Riedl M, Al-Ghazawi A, Soo C, Iarrobino R, Sexton DJ, TenHoor C, Kenniston JA, Faucette R, Still JG, Kushner H, Mensah R, Stevens C, Biedenkapp JC, Chyung Y, Adelman B: Inhibiting Plasma Kallikrein for Hereditary Angioedema Prophylaxis. N Engl J Med. 2017 Feb 23;376(8):717-728. doi: 10.1056/NEJMoa1605767. [Article]
- Wu MA: Lanadelumab for the treatment of hereditary angioedema. Expert Opin Biol Ther. 2019 Dec;19(12):1233-1245. doi: 10.1080/14712598.2019.1685490. Epub 2019 Nov 4. [Article]
Drug created at August 24, 2018 16:28 / Updated at December 13, 2023 13:52