Overview

Efavaleukin alfa is a fusion protein consisting of interleukin mutein fused to the C-terminus of an immunoglobulin G Fc domain by way of a G4S linker. It is under investigation in clinical trial NCT03422627 (Safety and Efficacy of AMG 592 in Subjects With Steroid Refractory Chronic Graft Versus Host Disease).

Indication

No indication information available.

Associated Conditions

No associated conditions information available.

Research Report

Published: Jun 17, 2025

Efavaleukin Alfa (AMG 592): A Comprehensive Analysis of a Treg-Selective IL-2 Mutein from Bench to Clinical Discontinuation

Section I: Executive Summary

Efavaleukin alfa (also known as AMG 592) represents a sophisticated example of rational drug design in modern biotechnology, developed by Amgen as a potential therapy for a range of autoimmune and inflammatory diseases. The molecule is a recombinant fusion protein, precisely engineered to address a fundamental challenge in immunology: how to leverage the therapeutic, immunosuppressive properties of Interleukin-2 (IL-2) without invoking its potent, pro-inflammatory effects. This was achieved by creating an IL-2 "mutein" with specific amino acid mutations to decrease its affinity for the intermediate-affinity IL-2 receptor subunit (IL-2Rβ) and increase its dependence on the high-affinity subunit (IL-2Rα, or CD25). This design preferentially targets regulatory T cells (Tregs), which constitutively express high levels of CD25 and are critical for maintaining immune tolerance. By fusing this IL-2 mutein to an immunoglobulin G1 (IgG1) Fc fragment, Amgen also engineered a significantly extended pharmacokinetic half-life, allowing for more convenient dosing regimens.

Continue reading the full research report

Clinical Trials

Title	Posted	Study ID	Phase	Status	Sponsor
A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of AMG 592 in Healthy Japanese Participants	2023/06/02	NCT05885451	Phase 1	Completed	Amgen
A Study to Evaluate the Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of AMG 592 in Healthy Participants	2023/05/24	NCT05873907	Phase 1	Completed	Amgen
Long-term Safety and Efficacy of Efavaleukin Alfa in Participants With Moderately to Severely Active Ulcerative Colitis	2023/01/05	NCT05672199	Phase 2	Terminated	Amgen
Safety and Efficacy of Efavaleukin Alfa in Participants With Moderately to Severely Active Ulcerative Colitis	2021/08/03	NCT04987307	Phase 2	Terminated	Amgen
Study of Efavaleukin Alfa in Healthy Chinese, Japanese, and Caucasian Participants	2021/08/03	NCT04987333	Phase 1	Completed	Amgen
Efficacy and Safety of Efavaleukin Alfa in Subjects With Active Systemic Lupus Erythematosus	2020/12/23	NCT04680637	Phase 2	Terminated	Amgen
Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Efavaleukin Alfa in Participants With Systemic Lupus Erythematosus	2018/03/01	NCT03451422	Phase 1	Completed	Amgen
Safety and Efficacy of Efavaleukin Alfa in Subjects With Steroid Refractory Chronic Graft Versus Host Disease	2018/02/06	NCT03422627	Phase 1	Terminated	Amgen
Safety and Efficacy of Efavaleukin Alfa in Subjects With Active Rheumatoid Arthritis	2018/01/25	NCT03410056	Phase 1	Terminated	Amgen

FDA Drug Approvals

Approved Product	Manufacturer	NDC Code	Route	Strength	Effective Date
No FDA approvals found for this drug.

EMA Drug Approvals

Approved Product	Authorization Holder	Status	Issued Date
No EMA approvals found for this drug.

HSA Drug Approvals

Approved Product	Manufacturer	Approval Number	Dosage Form	Strength	Approval Date
No HSA approvals found for this drug.

NMPA Drug Approvals

Approved Product	Company	Approval Number	Drug Type	Dosage Form	Approval Date
No NMPA approvals found for this drug.

PPB Drug Approvals

Approved Product	Registration No.	Company	Licence No.	Strength	Registration Date
No PPB approvals found for this drug.

TGA Drug Approvals

Approved Product	ARTG ID	Sponsor	Registration Type	Status	Registration Date
No TGA approvals found for this drug.

Health Canada Drug Approvals

Approved Product	Company	DIN	Dosage Form	Strength	Market Date
No Health Canada approvals found for this drug.

CIMA AEMPS Drug Approvals

Approved Product	Company	Registration Number	Pharmaceutical Form	Prescription Type	Status
No CIMA AEMPS (Spain) approvals found for this drug.

Philippines FDA Drug Approvals

Approved Product	Company	License Number	Dosage Form	Strength	Approval Date
No Philippines FDA approvals found for this drug.

Saudi SFDA Drug Approvals

Approved Product	Company	License Number	Dosage Form	Strength	Approval Date
No Saudi SFDA approvals found for this drug.

Malaysia NPRA Drug Approvals

Approved Product	Company	Registration Number	Dosage Form	Strength	Approval Date
No Malaysia NPRA approvals found for this drug.

UK EMC Drug Information

Medicine Name	MA Holder	MA Number	Pharmaceutical Form	Active Ingredient	Authorization Date
No UK EMC drug information found for this drug.

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Efavaleukin alfa