sirukumab

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Ligands
sirukumab

GtoPdb Ligand ID: 7989

Synonyms: CNTO 136 | CNTO-136 | Plivensia (proposed trade name)

Comment: Sirukumab is a monoclonal antibody directed against interleukin 6 (IL-6), in development as an immunomodulator for the treatment of rheumatoid arthritis (RA). It is also being tested as an immunopsychiatry therapy to treat depression.
Annotated peptide sequences for this antibody are available from its IMGT/mAb-DB record. Peptide sequence BLAST search using the heavy chain variable region of sirukumab provides100% match to a sequence claimed in patent US7560112 [1], and to the antibody with designation AME-19a.

No information available.

No information available.

Summary of Clinical Use
Phase 3 clinical trials assessing sirukumab for RA have been completed or are still ongoing (Oct 2017). Click here to link to ClinicalTrials.gov's listing of Phase 3 sirukumab trials. Other trials are collecting data in additional inflammatory conditions including lupus nephritis [6], cutaneous lupus erythematosus, systemic lupus erythematosus and giant cell arteritis. Research is beginning to indicate that the disease pathophysiology of depression may have an immune component [2-4], and reviewed in [9]. In particular, IL-6 has been identified as a susceptibility gene for major depressive disorder (MDD), with the promoter polymorphism rs1800797 showing a marginally significant correlation with cortical IL-6 expression [10]. This and other work (including [4]) has led to clinical trial of sirukumab as an adjunct to conventional antidepressant therapy in patients with MDD (see Phase 3 trial NCT02473289).

Summary of Clinical Use

Phase 3 clinical trials assessing sirukumab for RA have been completed or are still ongoing (Oct 2017). Click here to link to ClinicalTrials.gov's listing of Phase 3 sirukumab trials. Other trials are collecting data in additional inflammatory conditions including lupus nephritis [6], cutaneous lupus erythematosus, systemic lupus erythematosus and giant cell arteritis.
Research is beginning to indicate that the disease pathophysiology of depression may have an immune component [2-4], and reviewed in [9]. In particular, IL-6 has been identified as a susceptibility gene for major depressive disorder (MDD), with the promoter polymorphism rs1800797 showing a marginally significant correlation with cortical IL-6 expression [10]. This and other work (including [4]) has led to clinical trial of sirukumab as an adjunct to conventional antidepressant therapy in patients with MDD (see Phase 3 trial NCT02473289).

Mechanism Of Action and Pharmacodynamic Effects
IL-6 plays a role in the pathology of RA [5]. Sirukumab effectively acts to neutralise circulating IL-6, thereby inhibiting IL-6-induced activation of signalling pathways. By this mechanism sirukumab is expected to reduce the symoptoms of active RA. First-in-human PK, PD and safety of sirukumab was reported in 2011 [8].

Mechanism Of Action and Pharmacodynamic Effects

IL-6 plays a role in the pathology of RA [5]. Sirukumab effectively acts to neutralise circulating IL-6, thereby inhibiting IL-6-induced activation of signalling pathways. By this mechanism sirukumab is expected to reduce the symoptoms of active RA. First-in-human PK, PD and safety of sirukumab was reported in 2011 [8].

Clinical Trials
Clinical Trial ID	Title	Type	Source	Comment	References
NCT02473289	An Efficacy and Safety Study of Sirukumab in Participants With Major Depressive Disorder	Phase 2 Interventional	Janssen Research & Development, LLC