Nogapendekin alfa
Explore a selection of our essential drug information below, or:
Identification
- Summary
Nogapendekin alfa 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.
- Brand Names
- Anktiva
- Generic Name
- Nogapendekin alfa
- DrugBank Accession Number
- DB18740
- Background
Nogapendekin alfa is a human IL-15N72D variant. It is one of the active ingredients in Anktiva, a combination product also containing inbakicept, where a single inbakicept is complexed with two nogapendekin alfa components.6 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.7 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.4,5 Nogapendekin alfa, in combination with inbakicept, 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.4,5
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Interleukin-based products - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 12770.45 Da
- Sequences
- Not Available
- Synonyms
- Fusion protein consisting of il-15n72d and il-15rasu/fc
- Human interleukin 15 (72-aspartic acid) (human il-15 n72>d isoform)
- IL-15N72D
- Il-15n72d:il-15rec-su/fc soluble complex i
- Inbakicept nogapendekin alfa fusion complex
- Superagonist interleukin-15:interleukin-15 receptor alphasu/fc fusion complex alt-803
- External IDs
- ALT 803
- ALT-803
- ALT803
- IL-15N72D
- N-803
Pharmacology
- Indication
Nogapendekin alfa, in combination with inbakicept 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.6
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.- 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
Nogapendekin alfa 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.3
- 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.1 For example, it is a mediator of NK cell and T cell activation and proliferation.1 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).6 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).3,6 In other words, IL-15 is trans-presented by the IL-15Rα.6
Nogapendekin alfa is administered as a stable heterodimeric complex with inbakicept, which mimics the biological actions of IL-15.1 Nogapendekin alfa is a human IL-15N72D variant that has an asparagine (Asn) to aspartate (Asp) mutation at amino acid 72 (N72D), which grants the drug increased biological activity and a longer serum half-life compared to free IL-15.1,2,3 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.6 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.6
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.6
- 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
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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.Not Available
- 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 Anktiva Solution 400 ug/0.4mL Intravesical Altor BioScience, LLC, an indirect wholly-owned subsidiary of ImmunityBio, Inc. 2024-05-06 Not applicable US
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
- 7TK323DLA0
- CAS number
- 1622189-43-8
References
- General References
- 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]
- McBrien JB, Mavigner M, Franchitti L, Smith SA, White E, Tharp GK, Walum H, Busman-Sahay K, Aguilera-Sandoval CR, Thayer WO, Spagnuolo RA, Kovarova M, Wahl A, Cervasi B, Margolis DM, Vanderford TH, Carnathan DG, Paiardini M, Lifson JD, Lee JH, Safrit JT, Bosinger SE, Estes JD, Derdeyn CA, Garcia JV, Kulpa DA, Chahroudi A, Silvestri G: Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8(+) cells. Nature. 2020 Feb;578(7793):154-159. doi: 10.1038/s41586-020-1946-0. Epub 2020 Jan 22. [Article]
- 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]
- 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
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 Active Not Recruiting Not Available Non-Muscle-invasive Bladder Cancer (NMIBC) 1 somestatus stop reason just information to hide Not Available Terminated Not Available Pharmacokinetics 1 somestatus stop reason just information to hide 3 Active Not Recruiting Treatment Non-Small Cell Lung Cancer (NSCLC) 1 somestatus stop reason just information to hide 2 Active Not Recruiting Treatment Cervical Cancer / Colorectal Cancer / Gastric Cancer / Hepatocellular Carcinoma / Melanoma / Merkel Cell Carcinoma / Microsatellite Instability / Mismatch Repair Deficient (dMMR) / Non-Small Cell Lung Cancer (NSCLC) / Renal Cell Carcinoma (RCC) / Small Cell Lung Cancer (SCLC) / Squamous Cell Carcinoma of the Head and Neck (SCCHN) / Urothelial Carcinoma 1 somestatus stop reason just information to hide 2 Active Not Recruiting Treatment Colorectal Cancer / Small Intestine Cancer 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Solution Intravesical 400 ug/0.4mL - 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
- Receptor for interleukin-2. This beta subunit is involved in receptor mediated endocytosis and transduces the mitogenic signals of IL2. Probably in association with IL15RA, involved in the stimulation of neutrophil phagocytosis by IL15 (PubMed:15123770, PubMed:31040185)
- Specific Function
- coreceptor activity
- 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
- Common subunit for the receptors for a variety of interleukins. Probably in association with IL15RA, involved in the stimulation of neutrophil phagocytosis by IL15 (PubMed:15123770)
- Specific Function
- coreceptor activity
- 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 May 02, 2024 16:18 / Updated at May 15, 2024 05:42