SPEVIGO® approved for expanded indications in China and the US

• Generalized pustular psoriasis (GPP) is a rare, chronic, heterogenous neutrophilic inflammatory disease associated with skin and systemic symptoms, such as fever, pain, and fatigue^1,2,3,4
• In China, SPEVIGO^®’s expanded approval adds the reduction of occurrences of GPP in pediatric patients aged 12 and above weighing ≥40 kg, and adults⁵
• The US FDA’s approval expands the use of SPEVIGO^® to include the treatment of GPP in adults and pediatric patients aged 12 and above weighing ≥40 kg, making it the first targeted therapy that addresses the need for acute and chronic treatment for GPP patients⁶
• SPEVIGO^® is currently approved in 48 countries⁷

Boehringer Ingelheim today announced that the US Food and Drug Administration (FDA) has approved SPEVIGO^® (spesolimab-sbzo) injection for the treatment of generalized pustular psoriasis (GPP) in adults and pediatric patients aged 12 and above weighing ≥40 kg.⁵ This approval follows the Chinese National Medical Products Administration’s (NMPA) recent approval of SPEVIGO^® for the reduction of occurrence of generalized pustular psoriasis (GPP) in adolescents from 12 years of age with a body weight ≥40 kg and adults. SPEVIGO^® is a novel, humanized selective IgG1 antibody that binds to interleukin-36 receptor (IL-36R), a key part of a signaling pathway within the immune system shown to be involved in the cause of GPP.^8,9,10,11,12

The regulatory authorities’ decisions are majorly based on the positive results of the EFFISAYIL^® 2 clinical trial, a 48-week clinical trial that showed that SPEVIGO^® significantly reduced the risk of GPP flares by 84%, compared with placebo. In the trial with 123 patients, no flares were observed after week 4 of SPEVIGO^® subcutaneous treatment in the high-dose group (n=30).^13,14,15,16 In the Effisayil^® 2 trial, SPEVIGO^® was associated with an increased incidence (≥9 cases per 100 patient-years) of injection site reaction, urinary tract infection, arthralgia, and pruritus compared to placebo.

“Until now, people living with GPP have not had any approved options to treat their disease,” said Bruce Strober, MD, PhD, Clinical Professor, Dermatology, Yale University and Central Connecticut Dermatology. “SPEVIGO^® has the potential to redefine the treatment options for the patients we serve.”

Distinct from plaque psoriasis, GPP is a rare, chronic, heterogenous, inflammatory neutrophilic disease associated with painful skin manifestations and systemic symptoms, such as fever, pain, and fatigue.^1-4 GPP varies widely between individuals living with the condition, with symptoms presenting on a continuum, which means that it can present in either a persistent or a relapsing course.^2-4 GPP often requires emergency care and can lead to life-threatening complications, such as multi-organ failure and sepsis.¹⁷ GPP’s unpredictable nature can potentially have significant long-term impacts on quality of life for people living with it, and may cause fear and anxiety over the disease course.^3,18

“SPEVIGO^®’s new approvals constitute a fundamental change for people living with GPP, addressing their huge need for acute and chronic treatment,” said Carinne Brouillon, Member of the Board of Managing Directors and Head of Human Pharma at Boehringer Ingelheim. “Experiencing GPP can be mentally and physically devastating, leaving those affected with uncertainty and fear of the next episode. Therefore, expanding the treatment of GPP is a critical step towards addressing patients’ needs.”

About SPEVIGO^®

SPEVIGO^® is a novel, humanized, selective antibody that specifically blocks the activation of the IL-36R, a signaling pathway within the immune system shown to be involved in the pathogenesis of several autoinflammatory diseases, including GPP.^7-11 It is the first targeted therapy for the treatment of GPP and has been evaluated in the largest clinical program specifically for the treatment of patients with GPP.^10,19

What is SPEVIGO^®?

SPEVIGO^® is a prescription medicine used to treat generalized pustular psoriasis (GPP) in adults and children 12 years of age and older who weigh at least 88 pounds (40 kg). It is not known if SPEVIGO^® is safe and effective in children under 12 years of age or who weigh less than 88 pounds.

Important Safety Information

Do not receive SPEVIGO^® if you or your child have had a severe or life-threatening allergic reaction to spesolimab-sbzo or any of the ingredients in SPEVIGO^®.

What is the most important information I should know about SPEVIGO^®? SPEVIGO^® may cause serious side effects, including:

• Infections. SPEVIGO^® may lower the ability of your or your child’s immune system to fight infections and may increase your or your child’s risk of infections. Your healthcare provider should check you or your child for infections and tuberculosis (TB) before starting treatment with SPEVIGO^® and may treat you or your child for TB before you begin treatment with SPEVIGO^® if you have a history of TB or have active TB. Your healthcare provider should watch you or your child closely for signs and symptoms of TB during or after treatment with SPEVIGO^®. Tell your healthcare provider right away if you or your child have an infection or have symptoms of an infection during or after treatment with SPEVIGO^®, including:
  • fevers, chills, or sweats
  • muscle aches
  • cough
  • shortness of breath
  • blood in your phlegm (mucus)
  • burning when you urinate
  • urinating more often than normal
     
• Allergic reactions and infusion-related reactions. Serious allergic reactions may happen during or after your or your child’s SPEVIGO^® injection. If you or your child have a serious allergic reaction, your healthcare provider will stop treatment with SPEVIGO^®. If you or your child are given SPEVIGO^® in a vein (intravenously) and have an infusion- related reaction, your healthcare provider will stop your or your child’s SPEVIGO^® infusion and treat your or your child’s symptoms and may restart SPEVIGO^® at a slower infusion rate. Tell your healthcare provider or get emergency medical help right away if you or your child get any of the following symptoms during or after your or your child’s SPEVIGO^® injection:
  • feeling faint, dizzy, or lightheaded
  • swelling of your face, eyelids, lips, mouth, tongue, or throat
  • trouble breathing or throat tightness
  • fever
  • mouth sores
  • chest tightness
  • hives or skin rash that is different than the rash from generalized pustular psoriasis (GPP)
  • itching
  • swollen lymph nodes

Before you or your child receive SPEVIGO^®, tell your healthcare provider about all of your medical conditions, including if you or your child:

• have an infection that does not go away or that keeps coming back.
• have TB or have been in close contact with someone with TB.
• have recently received or are scheduled to receive an immunization (vaccine). You or your child should not receive live vaccines during and for at least 16 weeks after treatment with SPEVIGO^®. You or your child should be brought up to date with all vaccines before starting SPEVIGO^®.

• are pregnant or plan to become pregnant. It is not known if SPEVIGO^® can harm your or your child’s unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if SPEVIGO^® passes into your breast milk. Talk to your healthcare provider about the best way to feed your or your child’s baby during treatment with SPEVIGO^®.

Tell your healthcare provider about all the medicines you or your child take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What are the possible side effects of SPEVIGO^®?

The most common side effects of SPEVIGO^® given in a vein (intravenously) for GPP flare treatment include:

• feeling tired or weak
• nausea and vomiting
• headache
• itching or itchy bumps
• a collection of blood under the skin at the infusion site or bruising
• urinary tract infection

The most common side effects of SPEVIGO^® when given under the skin (subcutaneously) for treatment of GPP when not experiencing a flare include:

• redness, pain, swelling, hardening, hives, or warmth at the injection site
• joint pain
• urinary tract infection
• itching

These are not all of the possible side effects of SPEVIGO^®. Call your doctor for medical advice about side effects.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1‐800‐FDA‐1088.

Please see full Prescribing Information, Medication Guide, and Instructions for Use.

CL-SPG-100004 03.18.2024

About the EFFISAYIL^® 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:^10,18

• EFFISAYIL^® 1: A Phase II study that demonstrated treatment with a single intravenous dose of spesolimab significantly improved signs and symptoms of GPP in patients experiencing a flare, including rapid pustular and skin clearance. These results supported the approval of spesolimab as the first specific treatment for GPP flares in adults in major markets^10,20
• EFFISAYIL^® 2: A Phase IIb study that showed spesolimab significantly reduced the risk of GPP flares by 84% over 48 weeks compared to placebo. In the trial with 123 patients, no flares were observed after week 4 of spesolimab SC treatment  in the high-dose group (n=30)^12–15
• 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 trials²¹

About generalized pustular psoriasis (GPP)

GPP is a chronic, heterogenous, neutrophilic inflammatory disease associated with skin and systemic symptoms that is distinct from plaque psoriasis. GPP is recognized as a separate clinical entity from other forms of psoriasis, with the IL-36 pathway being a key driver of GPP and triggering response to treatment.¹ Prevalence of GPP is low and varies considerably across geographical regions, ranging from 1.76 to 124 patients per million persons in reports from key countries, including France, Japan, Sweden, and South Korea.² GPP can become life-threatening (mortality rates ranging from 2% to 16%) due to severe complications, such as multisystem organ failure and sepsis requiring urgent hospital care; many GPP patients also suffer from various comorbidities, which contribute to the ongoing burden for the patient and healthcare systems.^2,16,17 GPP symptoms appear unpredictable and present on a continuum, which greatly impacts a patient’s quality of life, and may cause fear and anxiety over the disease course, as well as long-term impacts on quality of life related to work/school, emotional health, social activities, and finances.^2,3,4

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 https://www.boehringer-ingelheim.com/.

March 2024
MPR-CRP-100327, MPR-US-102903

References:

¹Marrakchi S, Puig L. Pathophysiology of generalized pustular psoriasis. Am J Clin Dermatol. 2022;23:13–19.

²Prinz JC, Choon SE, Griffiths CEM, et al. Prevalence, comorbidities and mortality of generalized pustular psoriasis: A literature review. J Eur Acad Dermatol Venereol. 2023;37:256–273.

³Reisner DV, Johnsson FD, Kotowsky N, 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;23:65–71.

⁴Gooderham MJ, Van Voorhees AS, Lebwohl MG. An update on generalized pustular psoriasis. Expert Rev Clin Immunol. 2019;15:907–919.

⁵National Medical Products Administration. Drug approval document release, March 11 2024. 2024年03月11日药品批准证明文件送达信息发布 (nmpa.gov.cn) (Accessed 14 March 2024)

⁶Record on file.

⁷Record on file.

⁸Bassoy EY, Towne JE, Gabay C. Regulation and function of interleukin-36 cytokines. Immunol Rev. 2018;281:169–178.

⁹Marrakchi S, Guigue P, Renshaw BR, et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med. 2011;365:620–628.

¹⁰Ganesan 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.

¹¹Bachelez H, Choon SE, Marrakchi S, et al. Trial of spesolimab for generalized pustular psoriasis. N Engl J Med. 2021;385:2431–2440.

¹²Bachelez H, Choon SE, Marrakchi S, et al. Inhibition of the interleukin-36 pathway for the treatment of generalized pustular psoriasis. N Engl J Med. 2019;380:981–983.

¹³Boehringer 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).

¹⁴Morita A, Strober B, Burden AD, et al. Efficacy and safety of subcutaneous spesolimab for the prevention of generalised pustular psoriasis flares (Effisayil 2): an international, multicentre, randomised, placebo-controlled trial. Lancet. 2023;402:1541–1551.

¹⁵Gordon KB, Lebwohl M, Barker J, et al. Effect of spesolimab on achieving sustained disease remission in patients with generalized pustular psoriasis: Results from the Effisayil 2 study. European Academy of Dermatology & Venereology Congress; 2023; Berlin, Germany. Abstract P0731.

¹⁶Strober B, Augustin M, Tada Y, et al. Effect of high-dose subcutaneous spesolimab on skin manifestations: Results from the pivotal Effisayil 2 trial of flare prevention in generalized pustular psoriasis. European Academy of Dermatology & Venereology Congress; 2023; Berlin, Germany. Abstract 1732.

¹⁷Choon SE, Navarini AA, Pinter A. Clinical course and characteristics of generalized pustular psoriasis. Am J Clin Dermatol. 2022;23:21–29.

¹⁸Burden D, Mrowietz U, Skalicky AM, et al. Symptom experience and content validity of the Psoriasis Symptom Scale (PSS) in patients with generalized pustular psoriasis (GPP). Dermatol Ther (Heidelb). 2022;12:1367–1381.

¹⁹Choon SE, Lebwohl MG, Marrakchi S, et al. Study protocol of the global Effisayil 1 Phase II, multicentre, randomised, double-blind, placebo-controlled trial of spesolimab in patients with generalized pustular psoriasis presenting with an acute flare. BMJ Open. 2021;11:e043666.

²⁰Navarini A, Prinz JC, Morita A, et al. Spesolimab improves patient- reported outcomes in patients with generalized pustular psoriasis: Results from the Effisayil 1 study. J Eur Acad Dermatol Venereol. 2022; 37:730–736.

²¹Effisayil™ ON: A study to test long-term treatment with spesolimab in people with generalized pustular psoriasis who took part in a previous study. https://clinicaltrials.gov/study/NCT03886246. (Accessed 14 March 2024).