Inbakicept
Identification
- Summary
Inbakicept is an IL-15 receptor agonist used to treat BCG-unresponsive nonmuscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumours.
- Generic Name
- Inbakicept
- DrugBank Accession Number
- DB16479
- Background
Inbakicept is a dimeric human IL-15 receptor α (IL-15Rα) sushi domain/human IgG1 Fc fusion protein. It is one of the active ingredients in Anktiva, a combination product also containing nogapendekin alfa, where a single inbakicept is complexed with two nogapendekin alfa components.5 This combination product was approved by the FDA on April 22, 2024, for the treatment of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumours.6 Non-muscle invasive bladder cancer (NMIBC), which accounts for 75% of all bladder tumours, is commonly treated with transurethral resection of the bladder tumour and Bacillus Calmette-Guérin (BCG) immunotherapy; however, NMIBC is associated with a risk of disease recurrence or progression into advanced disease despite initial treatment with BCG.2,3 Inbakicept, in combination with nogapendekin alfa, mimics the actions of IL-15, stimulating the activation and proliferation of natural killer cells and CD8+ memory T cells, which also synergistically enhance BCG efficacy.2,3
- Type
- Biotech
- Groups
- Investigational
- Biologic Classification
- Protein Based Therapies
Fusion proteins - Protein Chemical Formula
- C2980H4624N800O894S28
- Protein Average Weight
- 66565.6 Da
- Sequences
>Inbakicept protein sequence ITCPPPMSVEHADIWVKSYSLYSRERYICNSGFKRKAGTSSLTECVLNKATNVAHWTTPS LKCIREPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHED PEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPA PIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Download FASTA FormatReferences:
- KEGG DRUG: Inbakicept [Link]
- Synonyms
- ALT-803 COMPONENT IL-15R.ALPHA.SU/FC FUSION PROTEIN
- Inbakicept
- INTERLEUKIN 15 RECEPTOR .ALPHA. CHAIN (HUMAN SUSHI DOMAIN-CONTAINING FRAGMENT) FUSION PROTEIN WITH IMMUNOGLOBULIN G1 (HUMAN FC FRAGMENT), DIMER
- INTERLEUKIN 15 RECEPTOR SUBUNIT ALPHA (HUMAN IL15R.ALPHA.) (1-65)-PEPTIDE (SUSHI DOMAIN-CONTAINING) FUSION PROTEIN WITH HUMAN IMMUNOGLOBULIN G1 FC FRAGMENT (232 C-TERMINAL RESIDUES) (66-297) (HOMO SAPIENS IGHG1*01, HINGE (71-80), CH2 (81-190), CH3 (191-2
- N-803 COMPONENT IL-15R.ALPHA.SU/FC FUSION PROTEIN
Pharmacology
- Indication
Inbakicept, in combination with nogapendekin alfa and Bacillus Calmette-Guérin (BCG), is indicated for the treatment of adult patients with BCG-unresponsive nonmuscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumours.5
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 Used as adjunct in combination to treat Bcg-unresponsive non-muscle invasive bladder cancer Combination Product in combination with: Nogapendekin alfa (DB18740) •••••••••••• ••••• ••••••••• •• •••• ••••••• ••••••••• •••••• Used as adjunct in combination to treat Bcg-unresponsive non-muscle invasive bladder cancer Combination Product in combination with: Nogapendekin alfa (DB18740) •••••••••••• ••••• ••••••••• •• •••• •••• ••••••••• •••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Inbakicept is a human IL-15 superagonist with immunostimulatory properties. In a preclinical bladder cancer model, the administration of inbakicept-nogapendekin alfa protein complex in combination with BCG led to reduced tumour burden and increased infiltration of stimulated CD8 + T cells and NK cells in the bladder.1
- Mechanism of action
Interleukin-15 (IL-15) regulates natural killer (NK) and memory T cell homeostasis, making it a notable therapeutic target for cancers and immune disorders such as HIV.4 For example, it is a mediator of NK cell and T cell activation and proliferation.4 IL-15 signals through a heterotrimeric receptor that is composed of the common gamma chain (γc) subunit, the beta chain (βc) subunit, and the IL-15-specific alpha subunit (IL-15Rα).5 IL-15 and IL-15Rα are typically presented by antigen-presenting cells, like monocytes and dendritic cells. These cells present IL-15 in a complex with IL-15Rα to neighbouring immune cells — specifically, natural killer (NK) cells and CD8+ T cells which have the CD122/CD132 receptor complex (shared IL-2/IL-15 receptor; βc and γc).1,5 In other words, IL-15 is trans-presented by the IL-15Rα.5
Inbakicept is administered as a stable heterodimeric complex with nogapendekin alfa, which mimics the biological actions of IL-15.4 Due to the mutation of nogapendekin alfa, the protein complex exhibits increased biological activity and a longer serum half-life compared to free IL-15.4,1 The binding of the nogapendekin alfa-inbakicept protein complex to IL-15 receptor promotes the proliferation and activation of NK, CD8+, and memory T cells without the proliferation of immuno-suppressive Treg cells.5 In a carcinogen-induced model of bladder cancer in immunocompetent rats, intravesicular administration of nogapendekin alfa-inbakicept alone or in combination with BCG showed anti-tumour activity.5
Target Actions Organism AInterleukin-2 receptor subunit beta agonistHumans ACytokine receptor common subunit gamma agonistHumans - Absorption
Systemic exposure of nogapendekin alfa-inbakicept complex was less than 100 pg/mL following the approved recommended dosage in all patients. This was below the lower limit of quantitation in all patients.5
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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- Toxicity
Not Available
- 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 softwareAmbroxol The risk or severity of methemoglobinemia can be increased when Inbakicept is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Inbakicept is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Inbakicept is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Inbakicept is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when Inbakicept is combined with Bupivacaine. - Food Interactions
- No interactions found.
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
- QN4LI58PJ5
- CAS number
- 2135939-52-3
References
- General References
- Rosser CJ, Tikhonenkov S, Nix JW, Chan OTM, Ianculescu I, Reddy S, Soon-Shiong P: Safety, Tolerability, and Long-Term Clinical Outcomes of an IL-15 analogue (N-803) Admixed with Bacillus Calmette-Guerin (BCG) for the Treatment of Bladder Cancer. Oncoimmunology. 2021 May 3;10(1):1912885. doi: 10.1080/2162402X.2021.1912885. [Article]
- de Jong FC, Laajala TD, Hoedemaeker RF, Jordan KR, van der Made ACJ, Boeve ER, van der Schoot DKE, Nieuwkamer B, Janssen EAM, Mahmoudi T, Boormans JL, Theodorescu D, Costello JC, Zuiverloon TCM: Non-muscle-invasive bladder cancer molecular subtypes predict differential response to intravesical Bacillus Calmette-Guerin. Sci Transl Med. 2023 May 24;15(697):eabn4118. doi: 10.1126/scitranslmed.abn4118. Epub 2023 May 24. [Article]
- Chamie K, Chang SS, Kramolowsky E, Gonzalgo ML, Agarwal PK, Bassett JC, Bjurlin M, Cher ML, Clark W, Cowan BE, David R, Goldfischer E, Guru K, Jalkut MW, Kaffenberger SD, Kaminetsky J, Katz AE, Koo AS, Sexton WJ, Tikhonenkov SN, Trabulsi EJ, Trainer AF, Spilman P, Huang M, Bhar P, Taha SA, Sender L, Reddy S, Soon-Shiong P: IL-15 Superagonist NAI in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer. NEJM Evid. 2023 Jan;2(1):EVIDoa2200167. doi: 10.1056/EVIDoa2200167. Epub 2022 Nov 10. [Article]
- Webb GM, Molden J, Busman-Sahay K, Abdulhaqq S, Wu HL, Weber WC, Bateman KB, Reed JS, Northrup M, Maier N, Tanaka S, Gao L, Davey B, Carpenter BL, Axthelm MK, Stanton JJ, Smedley J, Greene JM, Safrit JT, Estes JD, Skinner PJ, Sacha JB: The human IL-15 superagonist N-803 promotes migration of virus-specific CD8+ T and NK cells to B cell follicles but does not reverse latency in ART-suppressed, SHIV-infected macaques. PLoS Pathog. 2020 Mar 12;16(3):e1008339. doi: 10.1371/journal.ppat.1008339. eCollection 2020 Mar. [Article]
- FDA Approved Drug Products: ANKTIVA (nogapendekin alfa inbakicept-pmln) solution, for intravesical use [Link]
- FDA: FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer [Link]
- External Links
- Not Available
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 0 Not Yet Recruiting Treatment Renal Carcinoma / Renal Cell Carcinoma (RCC) / Urothelial Carcinoma 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Interleukin-2 receptor activity
- Specific Function
- Receptor for interleukin-2. This beta subunit is involved in receptor mediated endocytosis and transduces the mitogenic signals of IL2.
- Gene Name
- IL2RB
- Uniprot ID
- P14784
- Uniprot Name
- Interleukin-2 receptor subunit beta
- Molecular Weight
- 61116.59 Da
References
- Rosser CJ, Tikhonenkov S, Nix JW, Chan OTM, Ianculescu I, Reddy S, Soon-Shiong P: Safety, Tolerability, and Long-Term Clinical Outcomes of an IL-15 analogue (N-803) Admixed with Bacillus Calmette-Guerin (BCG) for the Treatment of Bladder Cancer. Oncoimmunology. 2021 May 3;10(1):1912885. doi: 10.1080/2162402X.2021.1912885. [Article]
- FDA Approved Drug Products: ANKTIVA (nogapendekin alfa inbakicept-pmln) solution, for intravesical use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Interleukin-2 binding
- Specific Function
- Common subunit for the receptors for a variety of interleukins.
- Gene Name
- IL2RG
- Uniprot ID
- P31785
- Uniprot Name
- Cytokine receptor common subunit gamma
- Molecular Weight
- 42286.68 Da
References
- Rosser CJ, Tikhonenkov S, Nix JW, Chan OTM, Ianculescu I, Reddy S, Soon-Shiong P: Safety, Tolerability, and Long-Term Clinical Outcomes of an IL-15 analogue (N-803) Admixed with Bacillus Calmette-Guerin (BCG) for the Treatment of Bladder Cancer. Oncoimmunology. 2021 May 3;10(1):1912885. doi: 10.1080/2162402X.2021.1912885. [Article]
- FDA Approved Drug Products: ANKTIVA (nogapendekin alfa inbakicept-pmln) solution, for intravesical use [Link]
Drug created at January 21, 2021 01:47 / Updated at May 07, 2024 12:49