Teclistamab
Identification
- Summary
Teclistamab is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T cell engager used to treat relapsed and refractory multiple myeloma in adults as monotherapy.
- Brand Names
- Tecvayli
- Generic Name
- Teclistamab
- DrugBank Accession Number
- DB16655
- Background
Teclistamab is an IgG4-PAA bispecific antibody that targets the CD3 receptor expressed on the surface of T cells and B cell maturation antigen (BCMA) expressed on malignant multiple myeloma cells.1 Teclistamab consists of an anti-BCMA arm and an anti-CD3 arm connected via two interchain disulfide bonds,1,7 allowing the drug to recruit CD3-expressing T cells to BCMA-expressing cells to promote T cell–mediated cytotoxicity.1
On August 24, 2022, the European Commission (EC) granted conditional marketing authorization of teclistamab as first-in-class bispecific antibody for the treatment of multiple myeloma, marking its first global approval.5 Teclistamab was later granted accelerated approval by the FDA on October 25, 2022.6
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- C6383H9847N1695O2003S40
- Protein Average Weight
- 146000.0 Da (approximate)
- Sequences
>anti-BCMA heavy chain QLQLQESGPGLVKPSETLSLTCTVSGGSISSGSYFWGWIRQPPGKGLEWIGSIYYSGITY YNPSLKSRVTISVDTSKNQFSLKLSSVTAADTAVYYCARHDGAVAGLFDYWGQGTLVTVS SASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS SGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPS VFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNST YRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVMHEALHNHYTQKSLSLSLGK
>anti-BCMA light chain SYVLTQPPSVSVAPGQTARITCGGNNIGSKSVHWYQQPPGQAPVVVVYDDSDRPSGIPER FSGSNSGNTATLTISRVEAGDEAVYYCQVWDSSSDHVVFGGGTKLTVLGQPKAAPSVTLF PPSSEELQANKATLVCLISDFYPGAVTVAWKGDSSPVKAGVETTTPSKQSNNKYAASSYL SLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
>anti-CD3 heavy chain EVQLVESGGGLVQPGGSLRLSCAASGFTFNTYAMNWVRQAPGKGLEWVARIRSKYNNYAT YYAASVKGRFTISRDDSKNSLYLQMNSLKTEDTAVYYCARHGNFGNSYVSWFAYWGQGTL VTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPA VLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAA GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQ FNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFLLYSKLTVDKS RWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
>anti-CD3 light chain QTVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQQKPGQAPRGLIGGTNKRAPGT PARFSGSLLGGKAALTLSGVQPEDEAEYYCALWYSNLWVFGGGTKLTVLGQPKAAPSVTL FPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSY LSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
Download FASTA FormatReferences:
- KEGG DRUG: Teclistamab [Link]
- Synonyms
- Teclistamab
- Teclistamab-cqyv
- External IDs
- JNJ 64007957
- JNJ-64007957
Pharmacology
- Indication
Teclistamab is indicated as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.4,7
Teclistamab is approved by the EC and FDA under conditional marketing authorization and accelerated approval, respectively. New evidence for this drug will be continuously monitored and reviewed, which will affect continued approval for the drug's indication.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Refractory multiple myeloma •••••••••••• ••••• ••••••• ••••••••••• ••••• •••••••• •••••••••• •••••••• ••••••••• •••••••••• •••••••• •••••••••• •••••••• •• ••••• ••••• ••••• ••••• •• •••••••• •••••••• •••••••• •••••••••• ••••••••• •••••••••• •••••••• •••••••••••••••• ••••• ••••••••• ••••••••• Treatment of Relapsed multiple myeloma •••••••••••• ••••• •••••••• •••••••••• ••••••••• •••••••••• •••••••• ••••••••• •••••••••• •••••••• •••••••••• •••••••• •••••••••••••••• ••••• •••••••••• ••••••• ••••••••••• ••••• •••••••• •••••••••• •••••••• •• ••••• ••••• ••••• ••••• •• •••••••• ••••••• ••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Teclistamab promotes T cell-mediated cytotoxicity against BCMA-expressing myeloma cells.1 It works to activate and redistribute T cells. Teclistamab treatment was associated with reduced B-cells and increased concentrations of serum cytokines, including IL-6, IL-10, and IL-2R.4,7
The soluble form of BCMA, which is produced through cleavage at the transmembrane domain by γ-secretase, in patients with multiple myeloma often correlates with disease progression and shorter overall survival rate.1 The majority of patients who received teclistamab had a reduction in soluble BCMA within one month of drug treatment.7
- Mechanism of action
B-cell maturation antigen (BCMA) is a member of the tumour necrosis factor family of receptors 1 expressed on the surface of B-lineage cells, as well as late-stage B cells and plasma cells.4,7 BCMA interacts with its ligands to activate survival signalling pathways such as NF-kappa B, STAT3, ERK1/2, and AKT/PI3K,2 and upregulates anti-apoptotic proteins to regulate B-cell maturation, proliferation, and survival.1 Besides B cells, BCMA is also widely expressed on multiple myeloma (MM) cells and supports the survival of MM cells, making it a promising therapeutic target for therapeutic agents for MM.1,2,3
Teclistamab is a bispecific T cell engaging antibody that targets the CD3 receptor, which is expressed on the surface of T cells, and BCMA, which is expressed on malignant cells. Due to its dual binding sites, teclistamab is able to draw CD3+ T cells in close proximity to BCMA+ cells, resulting in T cell activation and T cell-mediated cytotoxicity, which is mediated by secreted perforin and various granzymes stored in the secretory vesicles of cytotoxic T cells.4 This effect occurs without regard to T cell receptor specificity or reliance on major histocompatibility complex (MHC) Class 1 molecules on the surface of antigen presenting cells.4 Ultimately, teclistamab promotes the lysis and death of BCMA+ cells.4,7
Target Actions Organism AT-cell surface glycoprotein CD3 antibodyHumans ATumor necrosis factor receptor superfamily member 17 antibodyHumans - Absorption
The mean bioavailability following subcutaneous administration ranges from 69% to 72%.4,7
A study involved patients with multiple myeloma who received step-up doses of 0.06 mg/kg and 0.3 mg/kg followed by a subcutaneous dose of 1.5 mg/kg teclistamab once weekly. The mean accumulation ratio between the first and thirteenth weekly treatment dose of 1.5 mg/kg teclistamab was 4.2-fold for Cmax, 4.1-fold for Ctrough, and 5.3-fold for AUCtau. The mean (CV%) Cmax after administration of 1.5 mg/kg teclistamab was 23.8 mcg/mL (55%). The median (range) Tmax of teclistamab after the first and thirteenth treatment doses were 139 (19 to 168) hours and 72 (24 to 168) hours, respectively. Most subjects who received a dosage range of 0.08 mg/kg to 3 mg/kg teclistamab reached steady-state exposure after 12 weekly treatment doses.7
- Volume of distribution
The mean (CV%) volume of distribution of teclistamab was 5.63 L (29%). The volume of distribution of teclistamab increases with increasing body weight.7
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Based on non-compartmental analysis, the mean half-life (SD) was 3.8 (1.7) days (individual values ranging up to 8.8 days) following the first treatment intravenous dose of teclistamab.4
- Clearance
Teclistamab exhibits both time-independent and time-dependent clearance.4 The clearance of teclistamab increases with increasing body weight.7
In a study involving patients receiving step-up doses of 0.06 mg/kg and 0.3 mg/kg followed by a subcutaneous dose of 1.5 mg/kg teclistamab once weekly, the geometric mean (CV%) clearance is 0.472 L/day (64%) at the thirteenth dose. The mean (CV%) maximal reduction from baseline to the thirteenth treatment dose was 40.8% (56%). Patients who discontinue teclistamab-cqyv after the 13th treatment dose are expected to have a 50% reduction from Cmax in teclistamab-cqyv concentration at a median (5th to 95th percentile) time of 15 (7 to 33) days after Tmax and a 97% reduction from Cmax in teclistamab-cqyv concentration at a median time of 69 (32 to 163) days after Tmax.7
- Adverse Effects
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- Toxicity
There is no information regarding acute toxicity of teclistamab. The maximum tolerated dose of teclistamab has not been determined. In clinical studies, doses of up to 6 mg/kg have been administered. In the event of an overdose, the patient should be monitored for any signs or symptoms of adverse reactions, and appropriate symptomatic treatment should be instituted immediately.4
- 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 softwareImlifidase The therapeutic efficacy of Teclistamab can be decreased when used in combination with Imlifidase. - 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 Tecvayli Injection, solution 10 mg/ml Subcutaneous Janssen Cilag International Nv 2023-02-08 Not applicable EU Tecvayli Injection 90 mg/1mL Subcutaneous Janssen Biotech, Inc. 2022-10-25 Not applicable US Tecvayli Solution 153 mg / 1.7 mL Subcutaneous Janssen Pharmaceuticals 2023-10-20 Not applicable Canada Tecvayli Injection 10 mg/1mL Subcutaneous Janssen Biotech, Inc. 2022-10-25 Not applicable US Tecvayli Injection, solution 90 mg/ml Subcutaneous Janssen Cilag International Nv 2023-02-08 Not applicable EU
Categories
- Drug Categories
- 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 and other mammals
Chemical Identifiers
- UNII
- 54534MX6Z9
- CAS number
- 2119595-80-9
References
- General References
- Pillarisetti K, Powers G, Luistro L, Babich A, Baldwin E, Li Y, Zhang X, Mendonca M, Majewski N, Nanjunda R, Chin D, Packman K, Elsayed Y, Attar R, Gaudet F: Teclistamab is an active T cell-redirecting bispecific antibody against B-cell maturation antigen for multiple myeloma. Blood Adv. 2020 Sep 22;4(18):4538-4549. doi: 10.1182/bloodadvances.2020002393. [Article]
- Wu L, Huang Y, Sienkiewicz J, Sun J, Guiang L, Li F, Yang L, Golubovskaya V: Bispecific BCMA-CD3 Antibodies Block Multiple Myeloma Tumor Growth. Cancers (Basel). 2022 May 20;14(10). pii: cancers14102518. doi: 10.3390/cancers14102518. [Article]
- Cho SF, Anderson KC, Tai YT: Targeting B Cell Maturation Antigen (BCMA) in Multiple Myeloma: Potential Uses of BCMA-Based Immunotherapy. Front Immunol. 2018 Aug 10;9:1821. doi: 10.3389/fimmu.2018.01821. eCollection 2018. [Article]
- EMA Approved Drug Products: TECVAYLI (teclistamab) Subcutaneous Injection [Link]
- Johnson & Johnson: Janssen Marks First Approval Worldwide for TECVAYLI® (teclistamab) with EC Authorisation of First-in-Class Bispecific Antibody for the Treatment of Patients with Multiple Myeloma [Link]
- FDA: FDA approves teclistamab-cqyv for relapsed or refractory multiple myeloma [Link]
- FDA Approved Drug Products: TECVAYLI (teclistamab-cqyv) injection, for subcutaneous use [Link]
- External Links
- 2619426
- Wikipedia
- Teclistamab
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Not Yet Recruiting Treatment Multiple Myeloma (MM) / Refractory Cancer / Relapsed Cancer 1 3 Active Not Recruiting Treatment Multiple Myeloma (MM) 1 3 Recruiting Treatment Multiple Myeloma (MM) 2 3 Recruiting Treatment Relapsed/Refractory Multiple Myeloma (RRMM) 2 2 Active Not Recruiting Treatment Hematological Malignancy 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Subcutaneous 10 mg/1mL Injection Subcutaneous 90 mg/1mL Injection, solution Subcutaneous 10 mg/ml Injection, solution Subcutaneous 90 mg/ml Solution Subcutaneous 153 mg / 1.7 mL Solution Subcutaneous 30 mg / 3 mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antibody
- General Function
- Transmembrane signaling receptor activity
- Specific Function
- The CD3 complex mediates signal transduction.
Components:
References
- Pillarisetti K, Powers G, Luistro L, Babich A, Baldwin E, Li Y, Zhang X, Mendonca M, Majewski N, Nanjunda R, Chin D, Packman K, Elsayed Y, Attar R, Gaudet F: Teclistamab is an active T cell-redirecting bispecific antibody against B-cell maturation antigen for multiple myeloma. Blood Adv. 2020 Sep 22;4(18):4538-4549. doi: 10.1182/bloodadvances.2020002393. [Article]
- FDA Approved Drug Products: TECVAYLI (teclistamab-cqyv) injection, for subcutaneous use [Link]
- EMA Approved Drug Products: TECVAYLI (teclistamab) Subcutaneous Injection [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antibody
- General Function
- Receptor for TNFSF13B/BLyS/BAFF and TNFSF13/APRIL. Promotes B-cell survival and plays a role in the regulation of humoral immunity. Activates NF-kappa-B and JNK.
- Specific Function
- Signaling receptor activity
- Gene Name
- TNFRSF17
- Uniprot ID
- Q02223
- Uniprot Name
- Tumor necrosis factor receptor superfamily member 17
- Molecular Weight
- 20165.065 Da
References
- Pillarisetti K, Powers G, Luistro L, Babich A, Baldwin E, Li Y, Zhang X, Mendonca M, Majewski N, Nanjunda R, Chin D, Packman K, Elsayed Y, Attar R, Gaudet F: Teclistamab is an active T cell-redirecting bispecific antibody against B-cell maturation antigen for multiple myeloma. Blood Adv. 2020 Sep 22;4(18):4538-4549. doi: 10.1182/bloodadvances.2020002393. [Article]
- FDA Approved Drug Products: TECVAYLI (teclistamab-cqyv) injection, for subcutaneous use [Link]
- EMA Approved Drug Products: TECVAYLI (teclistamab) Subcutaneous Injection [Link]
Drug created at March 24, 2021 23:14 / Updated at September 12, 2023 18:32