CHMP recommends conditional marketing authorization for Spesolimab as first in class treatment option for generalized pustular psoriasis flares

The European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended the granting of a conditional market authorization* for Boehringer Ingelheim’s spesolimab as first in class treatment option for generalized pustular psoriasis (GPP) flares in adults. Spesolimab, marketed in the U.S. and in Japan as SPEVIGO^®, is a novel, 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 pathogenesis of GPP.^{1, 3, 5} 

“GPP flares are unpredictable, often require emergency care and can lead to serious, life-threatening complications such as shock and multisystem organ failure,” said Hervé Bachelez, M.D., Ph.D., study investigator and professor at the Department of Dermatology of the Saint-Louis University Hospital in Paris. “The positive opinion for spesolimab brings us one step closer to a new and first treatment option specifically designed to target the IL-36 pathway that is central to the pathogenesis of GPP.” 

“This positive recommendation recognizes spesolimab’s potential as a new targeted monoclonal antibody that could treat the underlying cause of GPP.  The accelerated development of spesolimab underscores our continued commitment to develop faster and more novel treatments for people with high unmet medical needs,” commented Carinne Brouillon, Member of the Board of Managing Directors, responsible for Human Pharma, Boehringer Ingelheim. 

The CHMP’s positive opinion on spesolimab is based on results from the pivotal EFFISAYIL^® 1 Phase II clinical trial.¹ In the 12-week trial, patients experiencing a GPP flare were treated with spesolimab or placebo. Most patients at the outset of the trial had a high, or very high, density of pustules, and impaired quality of life. After one week, 54% of patients treated with spesolimab showed no visible pustules compared to placebo (6%).¹ Adverse events were reported in 66% of patients treated with spesolimab and 56% of those receiving placebo after one week. Infections were reported by 17% and 6% of patients in the spesolimab and placebo groups respectively (at week one). Serious adverse events were reported in 6% of patients treated with spesolimab (at week one).¹ 

In common with other rare diseases, people living with GPP often do not receive a correct diagnosis and their symptoms identified as other forms of psoriasis. Recently, a Global Consensus Delphi Panel of experts concluded a systematic literature review that classified GPP as phenotypically, genetically, immunologically and histopathologically distinct from psoriasis vulgaris / plaque psoriasis. Gaining consensus on definitions, diagnosis and treatment goals is a positive advance to improve patient care.² 

About spesolimab 

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 pathogenesis of several autoinflammatory diseases, including GPP.^{1, 3, 5} 

It is the first treatment to specifically target the IL-36 pathway for the treatment of GPP flares that has been evaluated in a statistically powered, randomized, placebo-controlled trial. Spesolimab is also under investigation for the prevention of GPP flares and for the treatment of other neutrophilic skin diseases.^8,9 Spesolimab is marketed in the U.S. and Japan as SPEVIGO^®. In addition to the recent approvals in the U.S.A. and Japan and the CHMP positive opinion, spesolimab is currently under review by several other regulatory authorities. To date, spesolimab has received ‘Breakthrough Therapy Designation’ in the U.S., China and Taiwan, ‘Priority Review’ in the U.S., Canada and China, ‘Orphan Drug Designation’ in the U.S., Korea, Switzerland and Australia, ‘Rare Disease Designation’ and fast track in Taiwan, for the treatment of GPP flares. The European Medicines Agency initially validated the marketing authorization application for spesolimab in GPP in October 2021 and today’s positive opinion will bring hope to people with GPP living in Europe. 

About the EFFISAYIL^® 1 clinical trial¹ 

EFFISAYIL^® 1 (NCT03782792) was a 12-week, Phase II trial investigating patients with a GPP flare (N=53), randomly assigned 2:1 to a single 900 mg intravenous dose of spesolimab or placebo.¹ 

After one week, 54% of patients treated with spesolimab showed no visible pustules, compared to 6% of patients treated with placebo.¹ 

After 12 weeks more than 4 out of 5 patients (84.4%) had no visible pustules and clear/almost clear skin (81.3%).¹⁰ 

Adverse events were reported in 66% of patients treated with spesolimab and 56% of those receiving placebo after one week. Infections were reported by 17% and 6% of patients in the spesolimab and placebo groups respectively (at week one). Serious adverse events were reported in 6% of patients treated with spesolimab (at week one).¹ 

About generalized pustular psoriasis (GPP) 

GPP is a rare, heterogenous and potentially life-threatening neutrophilic skin disease, which is clinically distinct from plaque psoriasis.^{3, 11} GPP is caused by neutrophils (a type of white blood cell) accumulating in the skin, resulting in painful, sterile pustules all over the body.^{3, 11} The clinical course varies, with some patients having a relapsing disease with recurrent flares, and others having a persistent disease with intermittent flares.¹¹ While the severity of GPP flares can vary, if left untreated they can be life-threatening due to complications such as sepsis and multisystem organ failure.³ This chronic, systemic disease has a substantial quality of life impact for patients and places an increased burden on healthcare systems.¹² GPP has a varied prevalence across different geographical regions and more women are affected than men.^{3, 12-15} There is a high unmet need for treatments with an acceptable safety profile that can rapidly resolve the symptoms of GPP flares and prevent their reoccurrence. 

GPP flares can lead to hospitalization with serious complications, including heart failure, renal failure and sepsis, with the unpredictability and severity of these flares greatly affecting a person’s quality of life.^{2, 3} 

About Boehringer Ingelheim  

Boehringer Ingelheim is working on breakthrough therapies that transform lives, today and for generations to come. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term perspective. More than 52,000 employees serve over 130 markets in the three business areas, Human Pharma, Animal Health, and Biopharmaceutical Contract Manufacturing. Learn more at www.boehringer-ingelheim.com. 

Intended audiences 

This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business. 

References 

1. Bachelez H et al. Trial of Spesolimab for Generalized Pustular Psoriasis. NEJM. 2021;385:2431-40. 

2. Puig L, et al. Global consensus on the clinical course, treatment and management of generalized pustular psoriasis (GPP). Presented at the European Academy of Dermatology and Venereology (EADV) Congress, Milan, Italy, 7–10 September 2022: P1203.B. 

3. Crowley JJ, et al. A brief guide to pustular psoriasis for primary care providers, Postgrad Med. 2021;133(3):330-344. 

4. Augustin et al. A framework for improving the quality of care for people with psoriasis. JEADV 2012, 26 (Suppl. 4), 1-16. 

5. Furue K, et al. Highlighting Interleukin-36 Signalling in Plaque Psoriasis and Pustular Psoriasis. Acta Derm Venereol. 2018;98:5–13. 

6. Federal Drug Administration. New Drug Approvals for 2022. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761244s000lbl.pdf. Accessed September 2022. 

7. CHMP positive opinion. CHMP meeting highlights. https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-10-13-october-2022. 

8. ClinicalTrials.gov. A Study to Test Whether Spesolimab Helps People With a Skin Disease Called Hidradenitis Suppurativa. Available at: https://clinicaltrials.gov/ct2/show/NCT04762277. Accessed October 2022.  

9. ClinicalTrials.gov. A Study to Test Long-term Treatment With Spesolimab in People With Palmoplantar Pustulosis (PPP) Who Took Part in Previous Studies With Spesolimab. Available at: https://www.clinicaltrials.gov/ct2/show/NCT04493424. Accessed October 2022. 

10. Elewski B, et al. Sustained treatment effect of spesolimab over 12 weeks for generalized pustular psoriasis flares; results from the Effisayil 1 study. AAD Congress 2022, Poster 32924. 

11. Navarini AA, et al. European consensus statement on phenotypes of pustular psoriasis. JEADV. 2017;31:1792-1799. 

12. Hanna M, et al. Economic burden of generalized pustular psoriasis and palmoplantar pustulosis in the United States. Curr Med Res Opin. 2021. 37(5):735-742. 

13. Ohkawara A et al. Generalized pustular psoriasis in Japan: two distinct groups formed by differences in symptoms and genetic background. Acta Derm Venereol. 1996 Jan;76(1):68–71. 

14. Augey F, et al. Generalized pustular psoriasis (Zumbusch): a French epidemiological survey. Eur J Derm. 2006; 16(6):669-673. 

15. Jin H, et al. Clinical features and course of generalized pustular psoriasis in Korea. J Dermatol. 2015; 42(7):674-678.