Newly published trial results showed spesolimab significantly improved signs and symptoms of flare in rare, life-threatening skin disease, generalized pustular psoriasis 

Burlington, ON – [December 23] – Boehringer Ingelheim (Canada) Ltd. announced today the publication in the New England Journal of Medicine of new data from the pivotal Phase II Effisayil^TM 1 trial, which showed spesolimab, a first-in-class investigational treatment, significantly improved signs and symptoms of generalized pustular psoriasis (GPP) in patients experiencing a flare.¹  

GPP is a rare dermatological condition, characterized by the sudden appearance of multiple small blisters filled with pus on large areas of the body referred to as a flare.  A flare can be triggered by sunlight, upper respiratory infections, certain medications, the sudden withdrawal of steroids, stress, infections and pregnancy.^3,4 With GPP, previous flares do not indicate the severity or duration of the next GPP flare⁵.  This unpredictability makes it difficult to determine the course of the disease.⁵  

There is a high unmet need for treatments that can rapidly and completely resolve the symptoms of GPP flares. Flares greatly affect a person’s quality of life and can cause symptoms such as fever, chills, malaise, nausea and pain, or even life-threatening complications that may require emergency medical treatment.^2,6  

In the 12-week trial, 53 patients experiencing a GPP flare were treated with a single intravenous dose of 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. Results after one week demonstrated that:

• 54% of patients treated with spesolimab showed no visible pustules compared to 6% of those treated with placebo; and
• 43% of patients treated with spesolimab showed clear/almost clear skin compared to 11% of those in the placebo group.¹

Pustular and skin clearance continued for the duration of the study. This clearance was accompanied by clinically significant improvements in quality of life and symptoms, such as pain and fatigue, compared to placebo.¹

Over the 12-week duration of the study, non-serious infections rates were higher in the spesolimab group compared with placebo, with no pattern regarding pathogen and affected organs. Two patients reported to have drug reactions with eosinophilia and systemic symptoms.  

“GPP is a painful skin condition that is distressing to patients and their caregivers. GPP understandably affects many different aspects of a person’s lifestyle and has a big impact on quality of life,” said Dr. Kim Papp, MD, PhD, FRCPC, FAAD, Dermatologist and Founder and President of Probity Medical Research in Waterloo, Ontario. “These clinical trial results show that, in some patients, spesolimab has the potential to clear the skin of a GPP flare in one week.  Importantly, spesolimab continues to support the patient with sustained effect for up to 12 weeks.”

“At Boehringer Ingelheim, we are committed to finding transformative therapies to help advance treatment for people who urgently need them,” said Dr Emmanuelle Clerisme-Beaty, Head of Clinical Development and Medical Affairs, Dermatology, Boehringer Ingelheim. “The findings indicate that spesolimab may have a significant and positive impact on patients experiencing a GPP flare.”

The clinical program for spesolimab includes two other trials that are currently underway. First, the Effisayil-2 trial is designed to investigate spesolimab as a maintenance treatment to prevent the occurrence of GPP flares. The Effisayil-ON trial is an open label five-year extension study to investigate the longer-term efficacy and safety of spesolimab in patents with GPP.^7,8  

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 several autoimmune diseases pathogeneses, including GPP. ^9,10,11  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).^12,13

About the Effisayil^TM 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.¹  

After one week, 54% of patients (19 out of 35) treated with spesolimab showed no visible pustules (GPPGA score of 0), compared to 6% of patients (1 out of 18) treated with placebo (P<0.001). In addition, 43% of patients (15 out of 35) treated with spesolimab showed clear/almost clear skin (GPPGA score of 0/1), compared to 11% of patients (2 out of 18) in the placebo group (P=0.024).¹  

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

About generalized pustular psoriasis

GPP is a rare, heterogenous and potentially life-threatening neutrophilic skin disease, which is clinically distinct from plaque psoriasis.^9,14  GPP is caused by neutrophils (a type of white blood cell) accumulating in the skin, resulting in painful, sterile pustules all over the body.¹⁴ The clinical course varies, with some patients having a relapsing disease with recurrent flares, and others having a persistent disease with intermittent flares.¹⁴While 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.¹⁵  This chronic, systemic disease has a substantial quality of life impact for patients and healthcare burden.¹⁶  GPP has a varied prevalence across geographical regions and more women are affected than men.^9,17,18,19  

Boehringer Ingelheim (Canada) Ltd.  

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. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term perspective. Approximately 52,000 employees serve more than 130 markets in the three business areas, Human Pharma, Animal Health and Biopharmaceutical Contract Manufacturing. The Canadian headquarters of Boehringer Ingelheim was established in 1972 in Montreal, Quebec and is now located in Burlington, Ontario. Boehringer Ingelheim employs approximately 600 people across Canada. Learn more at www.boehringer-ingelheim.ca.

References

1- Bachelez H, et al. Trial of Spesolimab for Generalized Pustular Psoriasis. NEJM. 2021; N Engl J Med 2021;385:2431-40. 
2- Gooderham MJ, Van Voorhees AS, Lebwohl MG. An update on generalized pustular psoriasis. Expert Review of Clinical Immunology. 2019; 15(9): 907-919. doi: 10.1080/1744666X.2019.1648209 
3- Strober B, Kotowsky N, Medeiros R, et al. Unmet medical needs in the treatment and management of generalized pustular psoriasis flares: evidence from a survey of Corrona registry dermatologists. Dermatol Ther (Heidelb). 2021;11(2):529-541. doi:10.1007/s13555-021- 00493-0 
4- Kharawala S, Golembesky AK, Bohn RL, Esser D. The clinical, humanistic, and economic burden of generalized pustular psoriasis: a structured review. Expert Rev Clin Immunol. 2020;16(3):239-252. doi:10.1080/1744666X.2019.1708193

5- Bachelez H. Pustular psoriasis: the dawn of a new era. Acta Derm Venereol. 2020;100(3):adv00034. doi:10.2340/00015555-3388 
6- Sampogna F, et al. Measuring quality of life of patients with different clinical types of psoriasis using the SF-36. Br J Dermatol. 2006;154(5):844–849. 
7- ClinicalTrials.gov. A 5-year Study to Test BI 655130 in Patients With Generalized Pustular Psoriasis Who Took Part in Previous Studies With BI 655130. Available at https://clinicaltrials.gov/ct2/show/NCT03886246. Accessed: September 2021. 
8- ClinicalTrials.gov. A Study to Test Whether BI 655130 (Spesolimab) Prevents Flare-ups in Patients With Generalized Pustular Psoriasis. Available at: https://clinicaltrials.gov/ct2/show/NCT04399837. Accessed: September 2021. 
9- Crowley JJ, et al. A brief guide to pustular psoriasis for primary care providers, Postgraduate Medicine. 2021;133(3):330-344. 
10- Furue K, et al. Highlighting Interleukin-36 Signalling in Plaque Psoriasis and Pustular Psoriasis. Acta Derm Venereol. 2018;98:5–13. 
11- 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. 
12- 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 September 2021. 
13- 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: September 2021. 
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16- 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. 
17- 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. 
18- Augey F, et al. Generalized pustular psoriasis (Zumbusch): a French epidemiological survey. European Journal of Dermatology. 2006; 16(6):669-673. 
19- Jin H, et al. Clinical features and course of generalized pustular psoriasis in Korea. The Journal of Dermatology. 2015; 42(7):674-678.