Spesolimab prevents generalized pustular psoriasis flares in EFFISAYIL™ 2 trial

Today, at the 25^th World Congress of Dermatology (WCD), Boehringer Ingelheim presented new late-breaking data from the EFFISAYIL™ 2 trial showing that spesolimab significantly reduced the risk of GPP flares by 84% over 48 weeks compared to placebo. Furthermore, the trial with 123 patients demonstrated no flares after Week 4 of spesolimab treatment in the high dose group.¹

“EFFISAYIL™ 2 is the first and largest multinational randomized clinical trial to evaluate a treatment for the prevention of GPP flares,” said Bruce Strober, MD, PhD, Clinical Professor, Dermatology, Yale University and Central Connecticut Dermatology. “These results provide further compelling clinical evidence for the role IL-36 signaling plays in the pathogenesis of GPP. Moving forward, our hope is that dermatologists not only have a specific treatment for GPP flares, but that we can effectively prevent them in the future.”

GPP flares, characterized by painful pustules all over the body, often require emergency care and can lead to serious, life-threatening complications such as sepsis, shock and multisystem organ failure.³ In addition to the acute distress of a GPP flare, living with the uncertainty of the impact of the next flare can have a significant emotional burden on patients.⁴ 

“At IFPA we meet people living with GPP, who share their story of physical pain due to the symptoms of the disease, and the mental burden that comes with the flares,” said Frida Dunger Johnsson, Executive Director, IFPA. “Any progress made to ease the burden of the disease improves the quality of life of people living with GPP.”

"Through our comprehensive EFFISAYIL™ clinical program we have already delivered spesolimab as a major advancement for flaring GPP patients," said Carinne Brouillon, Head of Human Pharma, Boehringer Ingelheim. "The EFFISAYIL™ 2 trial results build on this success bringing us closer to achieving our ultimate goal of a flare-free future for everyone living with GPP."

Spesolimab (marketed as SPEVIGO®) has recently received Breakthrough Therapy Designation (BTD) from the U.S. Food and Drug Administration (FDA) and the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) as an investigational treatment for the prevention of GPP flares.

In the EFFISAYIL™ 2 trial, spesolimab was shown to have a favorable safety profile, with a similar incidence of patients with adverse events across spesolimab and placebo treatment arms.¹ 

About spesolimab

Spesolimab is a novel, humanized, selective antibody that specifically 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.^2,5,6 

It is the first approved treatment for GPP flares in adults that has been evaluated in a statistically-powered, randomized, placebo-controlled trial.² To date, SPEVIGO^® (spesolimab) has been approved by regulatory authorities in almost 40 countries including the US, Japan, Mainland China, and the European Union to treat GPP flares in adults.^7,8

Spesolimab is also under investigation for the treatment of other IL-36 mediated skin diseases.⁹

About the EFFISAYIL^TM clinical trial program

The EFFISAYIL™ clinical trial program evaluated the largest and broadest population of GPP patients in trials of a therapy specifically targeting the IL-36 pathway for GPP:^2,10,11 

• EFFISAYIL™ 1: A Phase II study that demonstrated treatment with a single intravenous dose of spesolimab achieved rapid pustular and skin clearance in patients with GPP flares. This effect was sustained over 12 weeks with up to two doses of spesolimab.² These results supported the approval of spesolimab (SPEVIGO^®) as the first specific treatment for GPP flares in adults in major markets.^2,7,8 
   
• EFFISAYIL™ 2: A Phase IIb study that showed spesolimab effectively prevented GPP flares, significantly reducing the risk of flare development up to 48 weeks with no flares after Week 4 of treatment in the high dose group.¹
   
• EFFISAYIL™ ON: An open-label extension study to evaluate the long-term safety and efficacy of spesolimab in patients with GPP, who have completed previous spesolimab trials.¹¹

About generalized pustular psoriasis (GPP)

GPP is a rare, chronic, often unpredictable and potentially life-threatening systemic neutrophilic skin disease, which is genetically and clinically distinct from plaque psoriasis.^5,12 GPP is caused by neutrophils (a type of white blood cell) accumulating in the skin, resulting in painful, sterile pustules all over the body.^5,12  The clinical course varies, with some patients having a relapsing disease with recurrent flares, and others having a persistent disease with intermittent flares.¹² While the severity of GPP flares can vary, if left untreated they can lead to hospitalization and become life-threatening due to complications such as sepsis and multisystem organ failure.⁵ This systemic disease has a substantial quality of life impact for patients and places an increased burden on healthcare systems.¹³ While epidemiological data vary between geographical regions, prevalence estimates vary from 0.18 to 12.4 per 100,000 with more women affected than men.¹⁴ There is a high unmet need for treatments with a favorable safety profile that can prevent the occurrence of GPP flares.^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, sustainable perspective. More than 53,000 employees serve over 130 markets in the two business units Human Pharma and Animal Health. 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.    Lebwohl M et al. Spesolimab for the prevention of generalized pustular psoriasis (GPP) flares: Results from the randomized, placebo-controlled trial Effisayil 2. Abstract presented at the 25th World Congress of Dermatology July 2023, Singapore.
2.    Bachelez H et al. Trial of spesolimab for generalized pustular psoriasis. NEJM. 2021;385:2431–2440.
3.    Puig L et al. Generalized pustular psoriasis: a global Delphi consensus on clinical course, diagnosis, treatment goals, and disease management. J Eur Acad Dermatol Venereol. 2023;37:737–752.
4.    Reisner DV, et al. Impact of Generalized Pustular Psoriasis from the Perspective of People Living with the Condition: Results of an Online Survey. Am J Clin Dermatol. 2022 Jan;23(Suppl 1):65-71. 
5.    Crowley JJ, et al. A brief guide to pustular psoriasis for primary care providers, Postgraduate Medicine. 2021;133:330–344.
6.    Furue K, et al. Highlighting interleukin-36 signaling in plaque psoriasis and pustular psoriasis. Acta Derm Venereol. 2018;98:5–13.
7.    Federal Drug Administration. New drug approvals for 2022. Available at: https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2022. Accessed June 2023.
8.    EC approval statement (data on file).  
9.    A study to test whether spesolimab helps people with a skin disease called hidradenitis suppurativa. Available at: https://clinicaltrials.gov/ct2/show/NCT04762277. Accessed June 2023.
10.    A study to test whether BI 655130 (spesolimab) prevents flare-ups in patients with generalized pustular psoriasis. Available at: www.clinicaltrials.gov/ct2/show/study/NCT04399837?term=Boehringer. Accessed June 2023.
11.    Effisayil ON: An open-label, long term extension study to assess the safety and efficacy of spesolimab treatment in patients with generalized pustular psoriasis (GPP). Available at: https://clinicaltrials.gov/ct2/show/NCT03886246?term=Effisayil&draw=2&rank=1. Accessed June 2023.
12.    Navarini AA, et al. European consensus statement on phenotypes of pustular psoriasis. JEADV. 2017;31:1792–1799. 
13.    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.
14.    Prinz JC, et al. Prevalence, comorbidities and mortality of generalized pustular psoriasis: A literature review. J Eur Acad Dermatol Venereol. 2023 Feb;37(2):256-273.