New spesolimab data show clinically significant improvement in patients with generalized pustular psoriasis (GPP) flares 

Ingelheim, Germany, March 28, 2022 – Boehringer Ingelheim announced today new data from the pivotal Effisayil™ 1 trial presented at the 2022 American Academy of Dermatology (AAD) Annual Meeting in Boston.

The Effisayil™ 1 trial, recently published in The New England Journal of Medicine, showed significant clearance of skin pustules in patients with GPP flares within the first week after treatment with a single intravenous dose of spesolimab versus placebo.⁴ This effect was sustained over 12 weeks, according to data presented at AAD, which found that 84.4% of patients had no visible pustules after the 12-week trial duration and 81.3% had clear/almost clear skin.¹

“GPP is an unpredictable, painful, and potentially life-threatening rare skin disease with no available approved or efficacious treatment options in most countries,” said Boni Elewski, M.D., trial investigator and Chair, Department of Dermatology at The University of Alabama School of Medicine. “The findings presented at this year’s AAD Annual Meeting show that the efficacy of spesolimab is sustained over 12 weeks, providing further evidence of the rapid benefit that spesolimab could bring to patients living with the burden of GPP flares.”

Generalized pustular psoriasis is a rare, potentially life-threatening neutrophilic skin disease, which is distinct from plaque psoriasis. GPP flares greatly affect a person’s quality of life and can lead to serious and life-threatening complications, including heart failure, renal failure, and sepsis.⁵

According to further data presented at the AAD Annual Meeting, rapid skin clearance observed following treatment with spesolimab was generally consistent across subgroups, including age, gender, ethnicity, and IL-36 gene mutation status.² Clinically significant improvements were shown within one week in patient-reported outcomes related to pain, fatigue, quality of life, and skin symptoms after treatment with spesolimab.³ 

“With these additional data, we are gaining a more complete picture of spesolimab as a potential first-in-class treatment for people living with GPP,” said Kay Tetzlaff, Head of Medicine, Therapeutic Area Inflammation, Boehringer Ingelheim. “GPP flares have a significant physical and emotional impact on a patient’s life. Our goal is to bring Spesolimab to patients as quickly as possible.”

Spesolimab is currently under review by regulatory authorities. To date, spesolimab has received Breakthrough Therapy Designation in the US, China mainland and Taiwan, Priority Review in the US and China mainland, Orphan Drug Designation in the US, Korea, Switzerland and Australia, Rare Disease Designation and fast track in Taiwan, for the treatment of GPP flares. The European Medicines Agency validated the marketing authorization application for spesolimab in GPP in October 2021 and the submission is currently under evaluation.

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.^5,6,7 It is the first investigational 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, such as palmoplantar pustulosis (PPP) and hidradenitis suppurativa (HS).^8,9

About the EffisayilTM 1 clinical trial

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. The primary endpoint was a GPP Physician Global Assessment (GPPGA) pustulation subscore of 0 (no visible pustules) at week one. The key secondary endpoint was a GPPGA score of 0/1 (clear/almost clear skin) at week one.⁴ 

After one week, 54% of patients treated with spesolimab showed no visible pustules (GPPGA pustulation subscore of 0), compared to 6% of patients treated with placebo. In addition, 43% of patients treated with spesolimab showed clear/almost clear skin (GPPGA total score of 0/1) after one week, compared to 11% of patients in the placebo group.⁴

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).⁴

About generalized pustular psoriasis

GPP is a rare, heterogenous and potentially life-threatening neutrophilic skin disease, which is clinically distinct from plaque psoriasis.^10,5 GPP is caused by neutrophils (a type of white blood cell) accumulating in the skin, resulting in painful, sterile pustules all over the body.¹⁰  The clinical course varies, with some patients having a relapsing disease with recurrent flares, and others having a persistent disease with intermittent flares.¹⁰  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.⁵ This chronic, systemic disease has a substantial quality of life impact for patients and increased healthcare burden.  GPP has a varied prevalence across geographical regions and more women are affected than men.^5,12,13,14
Currently no approved treatments are available for patients with GPP outside of Japan.

About Boehringer Ingelheim 

Boehringer Ingelheim is working on breakthrough therapies that improve the lives of humans and animals. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Around 52,000 employees serve more than 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 Elewski B, et al. Sustained treatment effect of spesolimab over 12 weeks for generalized pustular psoriasis flares; results from the Effisayil 1 study. Poster presented at AAD 2022 or Annual Meeting; March 2022; Boston.

² Burden D, et al. Efficacy of spesolimab for the treatment of GPP flares across prespecified patient subgroups in the Effisayil 1 study. Poster presented at AAD2022 or Annual Meeting; March 2022; Boston.

³ Navarini A, et al. Clinically significant improvements in patient-reported outcomes (PROs) in patients with a generalized pustular psoriasis (GPP) flare treated with spesolimab. Poster presented at AAD 2022 or Annual Meeting; March 2022; Boston.

⁴ Bachelez H et al. Trial of Spesolimab for Generalized Pustular Psoriasis. NEJM. 2021;385:2431-40.

⁵ Crowley JJ, et al. A brief guide to pustular psoriasis for primary care providers, Postgraduate Medicine. 2021;133(3):330-344.

⁶ Furue K, et al. Highlighting Interleukin-36 Signalling in Plaque Psoriasis and Pustular Psoriasis. Acta Derm Venereol. 2018;98:5–13.

⁷ Bachelez H, et al. Inhibition of the Interleukin-36 Pathway for the Treatment of Generalized Pustular Psoriasis. N Engl J Med. 2019; 380:981-983.

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 March 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://clinicaltrials.gov/ct2/show/NCT04493424. Accessed: March 2022. 

¹⁰ Navarini AA, et al. European consensus statement on phenotypes of pustular psoriasis. JEADV. 2017;31:1792-1799.

¹¹ 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.

¹² 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.

¹³ Augey F, et al. Generalized pustular psoriasis (Zumbusch): a French epidemiological survey. European Journal of Dermatology. 2006; 16(6):669-673.

¹⁴ Jin H, et al. Clinical features and course of generalized pustular psoriasis in Korea. The Journal of Dermatology. 2015; 42(7):674-678.