Generalized Pustular Psoriasis (GPP)

Generalized pustular psoriasis (GPP) is a rare skin disease characterized by the eruption of pustules that are often accompanied by systemic inflammation. Patients with GPP experience flares that can be triggered by infections, stress, medications, or even pregnancy.¹ 

There is a lack of approved treatments for GPP, as clinical trials focused on disease management are rare, especially randomized controlled studies. Available data supporting the safety and efficacy of current treatments derive mainly from case reports, case series, and nonrandomized studies.^2,3

The interleukin-36 (IL-36) signaling pathway has been identified as a central player in the pathogenesis of GPP, paving the way for the development of IL-36 pathway inhibitors that are currently under investigation in various clinical trials.²

Spevigo

Currently, the only approved treatment for GPP is Spevigo^® (spesolimab-sbzo); this medication was approved by the US Food and Drug Administration (FDA) in September 2022 for the treatment of GPP flares in adults.¹ Spevigo is a humanized, anti-IL-36 receptor (IL-36R) monoclonal antibody developed by Boehringer Ingelheim. The approval of this drug was based on the results of a phase 2 clinical trial, Effisayil-1.² 

Following the completion of the Effisayil-1 clinical trial at week 12, participants were eligible to enroll in a 5-year open-label extension clinical trial (Effisayil ON, NCT03886246).⁴ This long-term extension study sponsored by Boehringer Ingelheim is an open-label phase 2 clinical trial that will allow the evaluation of both the safety and efficacy of Spevigo in patients with GPP. This trial has already enrolled 131 participants and is expected to be completed by January 2028.⁴

A noninterventional study (NCT05670821) is expected to start in June 2023 in Japan, also sponsored by Boehringer Ingelheim, to evaluate the incidence of adverse drug reactions in patients on newly initiated Spevigo treatment.⁵

Read more about Spevigo

Imsidolimab

Imsidolimab, also known as ANB019, is a humanized monoclonal IL-36R antagonist developed by AnaptysBio Inc.² This experimental therapy is currently being evaluated in 2 phase 3 clinical trials, GEMINI-1 (NCT05352893) and GEMINI-2 (NCT05366855), both sponsored by AnapstysBio.^6,7 

GEMINI-1 is a randomized, double-blind, placebo-controlled trial that will evaluate the efficacy and safety of imsidolimab in adult patients with GPP. The trial will enroll about 45 participants with moderate to severe disease. Randomized participants will receive one dose of 750 mg of intravenous (IV) imsidolimab, one dose of 300 mg of IV imsidolimab, or a dose of placebo. The primary endpoint of this trial is the proportion of patients achieving clear or almost clear skin, determined by a Generalized Pustular Psoriasis Physician’s Global Assessment (GPPGA) score of 0 or 1 at week 4 of the trial.⁸ The completion of this clinical trial is expected by December 2023.⁶

Participants from the GEMINI-1 trial can be enrolled in GEMINI-2. In this trial, they will receive 200 mg of subcutaneous imsidolimab or a placebo every month, according to their profile as responders, partial responders, or nonresponders to treatment as determined in GEMINI-1. The GEMINI-2 phase 3 trial is a long-term extension study to evaluate the safety and efficacy of imsidolimab after 6 months of treatment.⁸ This clinical trial is expected to be completed by December 2026.⁷

Read more about GPP therapies

HB0034

A phase 1 clinical trial sponsored by Shanghai Huaota Biopharmaceutical Co, Ltd on the experimental therapy, HB0034, is currently recruiting. HB0034 is a recombinant humanized anti-IL-36R immunoglobulin G1 (IgG1) monoclonal antibody, and its safety, tolerability, pharmacokinetics, and efficacy will be evaluated in the multi-center, open-label, single-arm, phase 1b study (NCT05512598). The trial aims to recruit 10 participants with moderate to severe GPP and is expected to be completed by December 2023.⁹

Read more about GPP experimental therapies

References

1. Blair HA. Spesolimab: first approval. Drugs. 2022;82(17):1681-1686. doi:10.1007/s40265-022-01801-4
2. Rivera-Díaz R, Daudén E, Carrascosa JM, de la Cueva P, Puig L. Generalized pustular psoriasis: a review on clinical characteristics, diagnosis, and treatment. Dermatol Ther (Heidelb). 2023;13(3):673-688. doi:10.1007/s13555-022-00881-0
3. Bellinato F, Gisondi P, Marzano AV, et al. Characteristics of patients experiencing a flare of generalized pustular psoriasis: a multicenter observational study. Vaccines (Basel). 2023;11(4):740. doi:10.3390/vaccines11040740
4. Effisayil™ ON: a study to test long-term treatment with spesolimab in people with generalized pustular psoriasis who took part in a previous study. ClinicalTrials.gov. March 22, 2019. Updated May 31, 2023. Accessed May 31, 2023.
5. PMS of spesolimab I.V. in GPP patients with acute symptoms. ClinicalTrials.gov. January 4, 2023. Updated May 10, 2023. Accessed May 31, 2023.
6. Study to evaluate the efficacy and safety of imsidolimab (ANB019) in the treatment of subjects with GPP (GEMINI1). ClinicalTrials.gov. April 29, 2022. Updated May 5, 2022. Accessed May 31, 2023.
7. Long-term safety and efficacy of imsidolimab (ANB019) in subjects with generalized pustular psoriasis (GEMINI2). ClinicalTrials.gov. May 9, 2022. Updated September 14, 2022. Accessed May 31, 2023.
8. Imsidolimab. AnaptysBio. Accessed May 31, 2023.
9. HB0034 in patients with generalized pustular psoriasis (GPP). ClinicalTrials.gov. August 23, 2022. Updated November 14, 2022. Accessed May 31, 2023.

Reviewed by Hasan Avcu, MD, on 6/2/2023.

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Diana Diez Gaspar, PharmD, PhD

Diana earned her PhD and PharmD with distinction in the field of Medicinal and Pharmaceutical Chemistry at the Universidade do Porto. She is an accomplished oncology scientist with 10+ years of experience in developing and managing R&D projects and research staff directed to the development of small proteins fit for medical use.