Spesolimab significantly improves signs and symptoms of generalized pustular psoriasis

Generalized pustular psoriasis (GPP) is a rare, life-threatening skin condition for which there are no approved treatments. It is characterized by episodes of widespread eruptions of painful, sterile pustules (blisters of non-infectious pus).

There is a high unmet need for treatments that can rapidly and completely resolve the signs and symptoms of GPP flares.

Flares greatly affect a person’s quality of life and can lead to hospitalization with serious complications, including heart failure, renal failure, sepsis, and death.

A clinical trial has shown that spesolimab is a novel, humanized, selective antibody that blocks the activation of the interleukin-36 receptor (IL-36R), a signaling pathway within the immune system shown to be involved in the pathogeneses of several autoimmune diseases, including generalized pustular psoriasis.

The novel drug demonstrated rapid clearance of pustules in adult patients with generalized pustular psoriasis (GPP) experiencing a flare.

The study met the primary endpoint; 54% of patients had no visible pustules after a single dose of spesolimab, compared to 6% receiving a placebo at week one.

The bottom line appears to be that spesolimab is rapidly effective in the majority of patients within one week of its first intravenous infusion for patients suffering from generalized pustular psoriasis. This is significant because generalized pustular psoriasis is a life-threatening condition that compromises the integrity of the skin. Patients are frequently hospitalized and often die from sepsis or other complications.

The study’s senior author, Mark Lebwohl, MD, said, “Generalized pustular psoriasis is a rare life-threatening condition in which the protective functions of the skin are lost, leaving patients vulnerable to loss of electrolytes, nutrients, and fluids for the skin, causing high output cardiac failure, sepsis, and even death.

Until now, other treatments used for this condition have not been reliably effective and are often too slow for a condition that is so dangerous.

Spesolimab will hopefully be the first approved treatment in the United States for generalized pustular psoriasis, and we will finally have a reliable, rapidly effective treatment for this devastating disease.”

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Spesolimab (BI 655130) is a humanised monoclonal antibody that inhibits the action of the receptor IL-36R.2,3 IL-36 is a member of the pro-inflammatory cytokines family and is expressed in various types of cells including keratinocytes. The IL-36R potentiates the production of type-1 interferon through stimulation of leucocyte recruitment and innate immune inflammation.4 This signalling pathway may play a role in many inflammatory diseases.5

Spesolimab is currently in phase II clinical development for the treatment of GPP flares. In the phase II clinical trial (NCT03886246), there are two parts to the clinical development. Firstly, participants will receive an intravenous injection of spesolimab with the option for additional open-label administration at day 8, investigated for the treatment of flares in patients with GPP.

The second part of this clinical development includes a subcutaneous injections participant will receive for the prevention of GPP flares.1

CURRENT TREATMENT OPTIONS

There are two main types of systemic treatment for psoriasis. Biological treatments (mainly injections) which are usually used for severe psoriasis that has not responded well to other treatments and non-biological treatments (mainly orally by tablets or capsules). There is no specific NICE guidance or guideline for GPP. Current treatment options for psoriasis, as noted in NICE guideline include: 17,18

NICE recommends the following first line therapies:6

• Topical therapies e.g. corticosteroids, vitamin D, vitamin D analogues, dithranol and tar preparations

NICE recommends the following second line therapies:6

• Systemic non-biological agents such as ciclosporin, methotrexate and acitretin

NICE recommends the following third line therapies:6

• Tumour necrosis factor (TNF) antagonists e.g. adalimumab, etanercept and infliximab
• Interleukin-12 and IL-23 monoclonal antibody, ustekinumab

REFERENCES                   

1. Clinical Trials.gov. A 5-year Study to Test BI 655130 in Patients With Generalized Pustular Psoriasis Who Took Part in Previous Studies With BI 655130. https://ClinicalTrials.gov/show/NCT03886246 2019.
2. Clinical Trials.gov. A Study to Test BI 655130 in Patients With a Flare-up of a Skin Disease Called Generalized Pustular Psoriasis. 2018. Available from: https://clinicaltrials.gov/ct2/show/NCT03782792 [Accessed
3. Specialist Pharmacy Service NHS. Spesolimab. 2019. Available from: https://www.sps.nhs.uk/medicines/spesolimab/ [Accessed
4. Ratnarajah, K., Jfri A., Litvinov I. V., Netchiporouk E. Spesolimab: A Novel Treatment for Pustular Psoriasis. Journal of cutaneous medicine and surgery. 2020;24(2):199-200. Available from: https://pubmed.ncbi.nlm.nih.gov/32208020/ 27April2021
5. Boehringer Ingelheim. Novel antibody shows potential to transform treatment of rare form of psoriasis. 2019. Available from: https://www.boehringer-ingelheim.com/press-release/nejm-il- 36-phase-1-gpp-data [Accessed
6. NICE. Psoriasis: assessment and management. 2012. Available from: https://www.nice.org.uk/guidance/cg153 [Accessed
7. Clinical Trials.gov. Spesolimab. Available from: https://clinicaltrials.gov/ct2/results?term=spesolimab&age_v=&gndr=&type=&rslt=&phase=1 &phase=2&Search=Apply [Accessed
8. National Psoriasis Foundation. Guidelines for Treating Psoriatic Disease Patients. Available from: https://www.psoriasis.org/psoriatic-disease-patient-guidance/ [Accessed
9. Insitute for Quality and Efficiency in Health Care (IQWiG). Psoriasis: Overview. 2013. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279447/ [Accessed
10. Gooderham, M. J., Van Voorhees A. S., Lebwohl M. G. An update on generalized pustular psoriasis. Expert review of clinical immunology. 2019;15(9):907-19. Available from: https://www.tandfonline.com/doi/full/10.1080/1744666X.2019.1648209 24May2021
11. NIH Genetic and Rare diseases. Generalized pustular psoriasis. Available from: https://rarediseases.info.nih.gov/diseases/12819/generalized-pustular-psoriasis [Accessed
12. Mirza, H. A., Badri T. Generalized pustular psoriasis. StatPearls [Internet]. 2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK493189/ 27 April 2021
13. NIH MedlinePlus. Generalized pustular psoriasis. 2017. Available from: https://medlineplus.gov/genetics/condition/generalized-pustular-psoriasis/#causes [Accessed
14. Crowley, J. J., Pariser D. M., Yamauchi P. S. A brief guide to pustular psoriasis for primary care providers. Postgraduate Medicine. 2020:1-15. Available from: https://pubmed.ncbi.nlm.nih.gov/33118424/ 27 April 2021
15. NICE. Ixekizumab for treating moderate to severe plaque psoriasis. 2017. Available from: https://www.nice.org.uk/guidance/ta442/documents/final-scope [Accessed
16. NHS Digital. Hospital Admitted Patient Care Activity 2019-20. 2020. Available from: https://digital.nhs.uk/data-and-information/publications/statistical/hospital-admitted-patient- care-activity/2019-20 [Accessed
17. NHS. Psoriasis. 2018. Available from: https://www.nhs.uk/conditions/psoriasis/treatment/ [Accessed
18. British Skin Foundation. Psoriasis. Available from: https://knowyourskin.britishskinfoundation.org.uk/condition/psoriasis/ [Accessed
19. Lancashire Medicines Management Group. Guidelines for the Management of Psoriasis in Primary Care. 2017. Available from: https://www.fyldecoastccgs.nhs.uk/?wpfb_dl=1413&no_preview=1 [Accessed
20. Smith, C., Jabbar‐Lopez Z., Yiu Z., Bale T., Burden A., Coates L., et al. British Association of Dermatologists guidelines for biologic therapy for psoriasis 2017. British Journal of Dermatology. 2017;177(3):628-36. Available from: https://doi.org/10.1111/bjd.15665 28April 2021

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More information: Hervé Bachelez et al, Trial of Spesolimab for Generalized Pustular Psoriasis, New England Journal of Medicine (2021). DOI: 10.1056/NEJMoa2111563