CDSCO approves SPEVIGO® (spesolimab) - the first treatment option for generalized pustular psoriasis flares in adults

The Central Drugs Standard Control Organisation (CSDCO) in India has approved Boehringer Ingelheim’s SPEVIGO® (spesolimab) injection, a first-in-class treatment for generalised pustular psoriasis (GPP) flares in adults. Spesolimab 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, 4-6}  

In the EFFISAYIL® 1 Phase II global clinical trial1, 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%).²

In India, GPP presents a significant healthcare challenge, affecting individuals of all ages and demographics. While precise prevalence data for GPP in India is limited, GPP is widely recognized as a rare disease.

GPP is a rare and unpredictable systemic disease, with predominant skin symptoms, that is distinct from plaque psoriasis in both its disease mechanism and severity.^6,7 Given that it is so rare, recognizing the symptoms can be challenging, which lead to delays in diagnosis. It manifests with painful pus-filled blisters, redness, inflammation, and scaling on the skin, often accompanied by systemic symptoms like fever and fatigue. Timely diagnosis and treatment are crucial, yet challenges in misdiagnosis and delayed intervention persist, due to the rarity of GPP and its similarities to other skin conditions like psoriasis, leading to inadequate management and prolonged suffering for patients. Moreover, triggers for GPP flares, including stress, infections, certain medications, hormonal changes, and environmental factors, vary widely among individuals, making it challenging to predict and manage the condition effectively. 

“The approval of SPEVIGO® by the CDSCO represents a significant milestone in GPP management in India and underscores our commitment to bring novel therapies into the country. We often take our skin for granted. However, for a small percentage of people with a rare, lifelong skin disorder, living in constant anticipation of possible flares that could require emergency medical care is a harsh reality. Some patients often describe the feeling akin to ‘being on fire’. SPEVIGO®'s impact goes beyond treatment; it's about giving patients the chance to reclaim their lives. It presents a promising opportunity for enhancing effective management, quality of life, and patient outcomes in India, instilling hope for individuals grappling with GPP,” said Gagandeep Singh Bedi, Managing Director, Boehringer Ingelheim India.

Dr. Shraddha Bhure, Medical Director, Boehringer Ingelheim India highlighted the significance of this development. “GPP is a debilitating condition, with serious symptoms like flares and pustules that can significantly impact patients' ability to perform daily activities, often leading to significant morbidity and impaired quality of life. SPEVIGO®, a targeted therapy, has been shown to effectively reduce the severity of GPP flares, providing patients with an innovative treatment that specifically targets the underlying inflammation associated with GPP, thus providing relief from the distressing symptoms of the disease.”

People living with GPP often do not receive a correct or timely diagnosis and may have their symptoms identified as other forms of psoriasis. 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.³ The growing list of regulatory approvals for SPEVIGO® underlines that the Delphi panel’s vision of improved diagnosis and treatment for people with GPP is increasingly achievable.

Learn more at: 
https://www.boehringer-ingelheim.com/human-health/skin-diseases/gpp 
https://patient.boehringer-ingelheim.com/gpp/ 

About the Effisayil™ global clinical trial program
The Effisayil™ global 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:

• Effisayil™ 1: A Phase II study that demonstrated treatment with a single intravenous dose of spesolimab significantly improved signs and symptoms of generalized pustular psoriasis (GPP) in patients experiencing a flare. These results supported the approval of spesolimab (SPEVIGO®) as the first specific treatment for GPP flares in adults in major markets.^{8 - 18}
• Effisayil™ 2: The trial assesses the role of spesolimab in prevention of flares of GPP.^9,10,11,12
• 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.¹⁹

About generalized pustular psoriasis (GPP)
GPP is a rare, heterogenous and potentially life-threatening neutrophilic skin disease, which is global clinically distinct from plaque psoriasis.^{5, 20} GPP is caused by neutrophils (a type of white blood cell) accumulating in the skin, resulting in painful, sterile pustules all over the body.^5,7 The global clinical course varies, with some patients having a relapsing disease with recurrent flares, and others having a persistent disease with intermittent flares.⁷ 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.² This chronic, systemic disease has a substantial quality of life impact for patients and increased healthcare burden.⁶ GPP has a varied prevalence across different geographical regions and more women are affected than men.^5,21,22,23 There is a high unmet need for treatments that can rapidly resolve the symptoms of GPP flares and prevent their reoccurrence, with an acceptable safety profile.

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

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.in. 

¹Federal Drug Administration. New Drug Approvals for 2022. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761244s000lbl.pdf Accessed January 2023
³EC approval statement (data on file). 

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⁵Furue K, et al. Highlighting Interleukin-36 Signalling in Plaque Psoriasis and Pustular Psoriasis. Acta Derm Venereol. 2018;98:5–13.
⁶Crowley JJ, et al. A brief guide to pustular psoriasis for primary care providers, Postgraduate Medicine. 2021;133(3):330-344.
⁷Hanna 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.
⁸Ganesan R, Raymond EL, Mennerich D, et al. Generation and functional characterization of anti-human and anti-mouse IL-36R antagonist monoclonal antibodies. MAbs. 2017;9:1143–1154.
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¹¹Boehringer Ingelheim. Spesolimab prevented generalized pustular psoriasis flares in Effisayil™ 2 trial. 2023. https://www.boehringer-ingelheim.com/us/press-releases/effisayil-2-trial-results. (Accessed 14 March 2024).
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²¹Ohkawara 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.
²²Augey F, et al. Generalized pustular psoriasis (Zumbusch): a French epidemiological survey. Eur J Derm. 2006; 16(6):669-673.
²³Jin H, et al. Clinical features and course of generalized pustular psoriasis in Korea. J Dermatol. 2015; 42(7):674-678.