NAV

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
References:
  1. KEGG DRUG: Inbakicept [Link]
Download FASTA Format
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
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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

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used as adjunct in combination to treatBcg-unresponsive non-muscle invasive bladder cancerCombination Product in combination with: Nogapendekin alfa (DB18740)•••••••••••••••••••••••••• •• •••• ••••••• ••••••••• ••••••
Used as adjunct in combination to treatBcg-unresponsive non-muscle invasive bladder cancerCombination 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

TargetActionsOrganism
AInterleukin-2 receptor subunit beta
agonist
Humans
ACytokine receptor common subunit gamma
agonist
Humans
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.
DrugInteraction
Integrate drug-drug
interactions in your software
AmbroxolThe risk or severity of methemoglobinemia can be increased when Inbakicept is combined with Ambroxol.
ArticaineThe risk or severity of methemoglobinemia can be increased when Inbakicept is combined with Articaine.
BenzocaineThe risk or severity of methemoglobinemia can be increased when Inbakicept is combined with Benzocaine.
Benzyl alcoholThe risk or severity of methemoglobinemia can be increased when Inbakicept is combined with Benzyl alcohol.
BupivacaineThe 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
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. FDA Approved Drug Products: ANKTIVA (nogapendekin alfa inbakicept-pmln) solution, for intravesical use [Link]
  6. FDA: FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer [Link]
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingTreatmentRenal Carcinoma / Renal Cell Carcinoma (RCC) / Urothelial Carcinoma1

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

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Details1. Interleukin-2 receptor subunit beta
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
  1. 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]
  2. FDA Approved Drug Products: ANKTIVA (nogapendekin alfa inbakicept-pmln) solution, for intravesical use [Link]
Details2. Cytokine receptor common subunit gamma
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
  1. 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]
  2. 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