Spesolimab: A Review of the First IL-36 Blocker Approved for Generalized Pustular Psoriasis

Gaurav N Pathak; Emily Wang; Jimmy Dhillon; Prachi N Parikh; Reem Esseghir; Babar K Rao; Steven R Feldman

doi:10.1177/10600280241252688

Spesolimab: A Review of the First IL-36 Blocker Approved for Generalized Pustular Psoriasis

Ann Pharmacother. 2024 May 16:10600280241252688. doi: 10.1177/10600280241252688. Online ahead of print.

Authors

Gaurav N Pathak^{1

2}, Emily Wang¹, Jimmy Dhillon¹, Prachi N Parikh¹, Reem Esseghir¹, Babar K Rao^{1

3}, Steven R Feldman^{2

4

5

6}

Affiliations

¹ Department of Dermatology, Rutgers Robert Wood Johnson Medical School, Somerset, NJ, USA.
² Center for Dermatology Research, Department of Dermatology, School of Medicine, Wake Forest University, Winston-Salem, NC, USA.
³ Department of Dermatology, Rao Dermatology, Atlantic Highlands, NJ, USA.
⁴ Department of Pathology, School of Medicine, Wake Forest University, Winston-Salem, NC, USA.
⁵ Department of Social Sciences and Health Policy, School of Medicine, Wake Forest University, Winston-Salem, NC, USA.
⁶ Department of Dermatology, University of Southern Denmark, Odense, Denmark.

PMID: 38755971
DOI: 10.1177/10600280241252688

Abstract

Objective: This article reviews clinical trial data that assesses the safety, efficacy, and clinical application of spesolimab, an interleukin-36 (IL-36) blocker, for the treatment of generalized pustular psoriasis (GPP).

Data sources: A review of the literature was conducted using the search terms: "spesolimab," "BI 655130," and "spevigo" in MEDLINE (PubMed) and Clinicaltrials.gov from January 1, 1950 to October 31, 2023.

Study selection and data extraction: Relevant articles in English relating to the pharmacodynamics, pharmacokinetics, efficacy, and safety of spesolimab were included.

Data synthesis: In one phase 2 clinical trial evaluating single dose IV spesolimab for GPP flares at day 8, 54% of patients receiving spesolimab had a GPP physician global assessment (GPPGA) pustulation subscore of 0, and 43% had a GPPGA total score of 0 compared with 6% and 11% for the placebo group, respectively. Another phase 2 clinical trial assessing subcutaneous spesolimab found 23% of patients in low-dose, 29% in medium-dose, and 10% of high-dose spesolimab had flares by week 48 compared with 52% of the placebo group. Hazard ratios for time to GPP flare compared with placebo were 0.16 (P = 0.0005), 0.35 (P = 0.0057), and 0.47 (P = 0.027) for the spesolimab groups, respectively. Infection rates were similar across treatment and placebo groups, and severe adverse events such as drug reactions with eosinophilia and systemic symptom (DRESS), cholelithiasis, and breast cancer occurred with spesolimab.

Relevance to patient care and clinical practice in comparison to existing drugs: Spesolimab is a first-in-class IL-36 monoclonal antibody receptor antagonist approved for the treatment of acute GPP flares. It is a safe and effective therapeutic agent in preventing future GPP flares, with no current comparator trials with other GPP agents.

Conclusion: Spesolimab is a safe and effective treatment for acute GPP flares in adults. Future clinical trials can establish safety and efficacy compared with other agents.

Keywords: GPP; generalized pustular psoriasis; spesolimab; spevigo.

Publication types

Review