risankizumab

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Ligands
risankizumab

GtoPdb Ligand ID: 8922

Synonyms: ABBV-066 | BI 655066 | BI-655066 | risankizumab-rzaa | Skyrizi®

risankizumab is an approved drug (Japan, FDA & EMA (2019))

Comment: Risankizumab (research code BI 655066) is a humanised monoclonal antibody targeting interleukin 23A (IL-23A) [11]. It was developed through collaboration between Boehringer Ingelheim and AbbVie for the treatment of autoinflammatory diseases.
Peptide sequence and structural information for this antibody are available from its IMGT/mAb-db record.

No information available.

No information available.

Summary of Clinical Use
Results from the first-in-human proof-of-concept trial in patients with psoriasis were reported by Krueger et al. in 2015 [9]. Phase 3 trial results in psoriasis patients were published in 2018 [8]. FDA and EMA approvals were granted in 2019 and it is also approved in Japan and Canada. Risankizumab therapy is indicated for patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy (Japan's authorisation additionally includes treatment of generalized pustular psoriasis, erythrodermic psoriasis and psoriatic arthritis). Investigations are ongoing in other autoinflammatory conditions. Click here to link to ClinicalTrials.gov's full list of risankizumab trials. In May 2022, two studies reported results from phase 3 RCTs of risankizumab for Crohn's disease [4,6]. The NCT04524611 (SEQUENCE) study is directly comparing risankizumab and ustekinumab in participants with moderate to severe Crohn's disease and for whom anti-TNF therapy has failed.

Summary of Clinical Use

Results from the first-in-human proof-of-concept trial in patients with psoriasis were reported by Krueger et al. in 2015 [9]. Phase 3 trial results in psoriasis patients were published in 2018 [8]. FDA and EMA approvals were granted in 2019 and it is also approved in Japan and Canada. Risankizumab therapy is indicated for patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy (Japan's authorisation additionally includes treatment of generalized pustular psoriasis, erythrodermic psoriasis and psoriatic arthritis). Investigations are ongoing in other autoinflammatory conditions. Click here to link to ClinicalTrials.gov's full list of risankizumab trials.

In May 2022, two studies reported results from phase 3 RCTs of risankizumab for Crohn's disease [4,6]. The NCT04524611 (SEQUENCE) study is directly comparing risankizumab and ustekinumab in participants with moderate to severe Crohn's disease and for whom anti-TNF therapy has failed.

Mechanism Of Action and Pharmacodynamic Effects
The IL-23/IL-17 axis plays an important role in the development of chronic inflammation [7], with potential genetic links between the IL-23 receptor (IL-23R) or its ligand identified in inflammatory diseases such as psoriasis, inflammatory bowel disease [10], and graft-versus-host disease [2-3,5,12]. Signaling through the IL-23R induces Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) phosphorylation and leads to increased levels of the inflammatory cytokines IL-17 and IL-23. Risankizumab binds to the p19 subunit of IL-23, IL-23A, preventing receptor activation and thereby disrupting the IL-23/IL-17 axis.

Mechanism Of Action and Pharmacodynamic Effects

The IL-23/IL-17 axis plays an important role in the development of chronic inflammation [7], with potential genetic links between the IL-23 receptor (IL-23R) or its ligand identified in inflammatory diseases such as psoriasis, inflammatory bowel disease [10], and graft-versus-host disease [2-3,5,12]. Signaling through the IL-23R induces Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) phosphorylation and leads to increased levels of the inflammatory cytokines IL-17 and IL-23. Risankizumab binds to the p19 subunit of IL-23, IL-23A, preventing receptor activation and thereby disrupting the IL-23/IL-17 axis.

Clinical Trials
Clinical Trial ID	Title	Type	Source	Comment	References
NCT03104413	A Study to Assess the Efficacy and Safety of Risankizumab in Participants With Moderately to Severely Active Crohn's Disease Who Failed Prior Biologic Treatment	Phase 3 Interventional	AbbVie	The MOTIVATE study	4
NCT03105128	A Study of the Efficacy and Safety of Risankizumab in Participants With Moderately to Severely Active Crohn's Disease	Phase 3 Interventional	AbbVie	The ADVANCE study	4
NCT00001693	Phase I-II Multiple-Dose Safety and Efficacy Study of a Selective Inhibitor of Cyclooxygenase - 2 (SC-58635) in Hereditary Non-Polyposis Colorectal Cancer (HNPCC) Patients and Carriers	Phase 1 Interventional	National Institutes of Health Clinical Center (CC)	The FORTIFY maintenance trial.	6