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SPEVIGO SC 
(subcutaneous) was 
evaluated in the 
Effisayil® 2 trial1,2

EFFISAYIL 2 was the first trial to study subcutaneous spesolimab in GPP patients when not experiencing a flare1,2

Effisayil® 2 Clinical Trail of Spevigo® SC Study Design

Primary endpoint

Time to first GPP flare, up to Week 483 

GPP flare was defined as an increase of ≥2 in GPPPGA total score from baseline and a GPPPGA pustulation subscore ≥2.3 Any use of flare treatment with open-label intravenous spesolimab or other investigator-prescribed medication to treat GPP worsening was considered a GPP flare event.1

  • *
    An optional second dose of SPEVIGO 900 mg IV could be administered to patients with persistent flare symptoms at Day 8.1
  • †
    Patients who received 300 mg SC OL SPEVIGO q12w had the option to escalate to 300 mg SC q4w.1
  • ‡
    Patients were given the opportunity to enter the OLE trial (EFFISAYIL ON, 1368-0025) once they completed the treatment period in the study up to Week 48 (ie, no premature discontinuation of trial treatment), agreed to participate in the OLE trial, and met the trial eligibility criteria.1

There were 3 doses of SPEVIGO SC (n=92) or placebo (n=30) in subjects with generalized pustular psoriasis.1

While a 600 mg LD dose of SPEVIGO followed by 300 mg every 12 weeks dosage and a 300 mg LD of SPEVIGO followed by 150 mg every 12 weeks dosage were studied in Study EFFISAYIL 2, these dosages are not approved.3

GPP=generalized pustular psoriasis; GPPPGA=Generalized Pustular Psoriasis Physician Global Assessment; IV=intravenous; LD=loading dose; OL=open label; OLE=open-label extension; q4w=every 4 weeks; q12w=every 12 weeks; R=randomization; SC=subcutaneous.

Endpoint summary1,3

Spevigo® SC Effisayil® 2 Study Design Endpoint Summary

Adolescents and adults 12 to 75 years of age (weighing 40 kg) with a documented diagnosis of
generalized pustular psoriasis (GPP), as defined by the European Rare and Severe Psoriasis Expert
Network (ERASPEN)4:

  • History of GPP* with ≥2 past GPP flares with fresh pustulation (new appearance or worsening)2†
  • Generalized Pustular Psoriasis Physician Global Assessment total score of 0 or 1 at screening and randomization4
  • Patients not on concurrent GPP treatment at randomization1:
    – Must have had ≥2 moderate-to-severe flares in the previous year,* ≥1 of which must have been associated with systemic symptoms (fever, elevated C-reactive protein [CRP] or white blood cell count, asthenia, and/or myalgia)
  • Patients on concurrent GPP treatment within 12 weeks prior to randomization4: 
    – Must have a history of flaring during or after dose reduction or discontinuation of concurrent treatment 
    – Patients on concurrent treatment with retinoids, methotrexate, and/or cyclosporin must stop this treatment on the day of randomization

Patients were excluded if they presented with:

  • Synovitis, acne, pustulosis, hyperostosis, osteitis syndrome
  • Primary erythrodermic psoriasis vulgaris
  • Severe, progressive, or uncontrolled hepatic disease
  • Treatment with any defined restricted medication, any drug considered by the investigator to interfere with the safe conduct of the study, or prior exposure to SPEVIGO or another interleukin-36 receptor inhibitor biologic
  • Biologic treatments must not be taken for 12 weeks or 5 half-lives (whichever is shorter) prior to randomization. Systemic immunomodulatory treatments (eg, corticosteroids) are not permitted 4 weeks prior to randomization
  • *
    Patients included had a documented history of moderate-to-severe GPP flares.1
  • †
    At screening, diagnosis of GPP was confirmed using ERASPEN criteria, and the patients must have had previous evidence of systemic signs and 
    symptoms for past GPP flares.4

The Generalized Pustular Psoriasis Physician Global 
Assessment (GPPPGA) is used to evaluate flare symptoms 
and treatment efficacy5

The GPPPGA score is adapted from the Physician Global Assessment, a tool physicians use 
to assess psoriatic lesions. The GPPPGA is used to assess the severity of pustules, erythema, and 
scaling, using a 5-point scale ranging from 0 to 4, with higher score indicating greater disease severity.

To determine a patient’s GPPPGA total score:

Body With GPP Icon

Step 1

Examine and assess the severity 
of pustules, erythema, and 
scaling

GPPPGA Checklist Icon

Step 2

Apply a score to each individual 
component

GPPPGA Check Mark Icon

Step 3

Calculate the average to 
determine the total score

The GPPPGA total score is determined by average subscores of pustules, erythema, and scaling. The components are graded separately. The average is calculated and the GPPPGA total score is determined from the average composite score of pustules, erythema, and scaling: 0 (0 for all 3 components), 1 (average is >0 to <1.5), 2 (average is 1.5 to <2.5), 3 (average is 2.5 to <3.5), or 4 (average is: ≥3.5). To receive a score of 0 or 1, the patient must also be afebrile.

The GPPPGA is used to assess flare symptoms and treatment efficacy5

Spevigo® SC Effisayil® 2 Study Design Endpoint Summary

Choon SE, et al. BMJ Open. 2021;11(3):e043666. doi:10.1136/bmjopen-2020-043666. All images ©2021 Boehringer Ingelheim International, GmbH. All rights reserved.

The GPPPGA total score is the calculated average of the composite scores for pustules, erythema, 
and scaling skin5

  • *
    Flare control defined as GPPPGA total score ≤1 and was reported for the 12-week study period.6
  • †
    To receive a score of 0 or 1, the patient should be afebrile, in addition to skin presentation requirements.5

References

  1. Morita 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(10412):1541-1551. doi:10.1016/S0140-6736(23)01378-8

  2. Strober B, Mostaghimi A, Anadkat MJ, et al. Measuring GPPGA, pain, symptom, and quality of life index scores in untreated generalized pustular psoriasis: results from the placebo group of the Effisayil 2 trial. Poster presented at:
    Winter Clinical Dermatology Conference; January 12-17, 2024; Honolulu, HI.

  3. SPEVIGO® [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; March 2024.

  4. Morita A, Choon SE, Bachelez H, et al. Design of Effisayil 2: a randomized, double-blind, placebo-controlled study of spesolimab in preventing flares in patients with generalized pustular psoriasis. Dermatol Ther (Heidelb).
    2023;13(1):347-359. doi:10.1007/s13555-022-00835-6

  5. Choon 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(3):e043666. doi:10.1136/bmjopen-2020-043666

  6. Bachelez H, Choon SE, Marrakchi S, et al; for the Effisayil 1 Trial Investigators. Trial of spesolimab for generalized pustular psoriasis. N Engl J Med. 2021;385(26):2431-2440. doi:10.1056/NEJMoa2111563-043666

INDICATION

SPEVIGO is indicated for the treatment of generalized pustular psoriasis (GPP) in adults and pediatric patients 12 years of age and older and weighing at least 40 kg. 

 

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

SPEVIGO is contraindicated in patients with severe or life-threatening hypersensitivity to spesolimab-sbzo or to any of the excipients in SPEVIGO. Reported hypersensitivity reactions have included drug reaction with eosinophilia and systemic symptoms (DRESS). 

WARNINGS AND PRECAUTIONS 

Infections: SPEVIGO may increase the risk of infections. In patients with a chronic infection or a history of recurrent infection, consider the potential risks and expected clinical benefits of treatment prior to prescribing SPEVIGO. Treatment with SPEVIGO is not recommended in patients with any clinically important active infection until the infection resolves or is adequately treated. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur during or after treatment with SPEVIGO. If a patient develops a clinically important active infection, discontinue SPEVIGO therapy until the infection resolves or is adequately treated.

Risk of Tuberculosis: Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with SPEVIGO. Avoid use of SPEVIGO in patients with active TB infection. Consider initiating anti-TB therapy prior to initiating SPEVIGO in patients with latent TB or a history of TB in whom an adequate course of treatment cannot be confirmed. Monitor patients for signs and symptoms of active TB during and after SPEVIGO treatment. 

Hypersensitivity and Infusion-Related Reactions:

  • SPEVIGO-associated hypersensitivity reactions may include immediate reactions, such as anaphylaxis, and delayed reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS).
  • Drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported in clinical trials with spesolimab-sbzo in subjects with GPP.
  • If a patient develops signs of anaphylaxis or other serious hypersensitivity, discontinue SPEVIGO immediately and initiate appropriate treatment.
  • If a patient develops mild or moderate hypersensitivity during an intravenous infusion or other infusion-related reactions, stop SPEVIGO infusion and consider appropriate medical therapy (eg, systemic antihistamines and/or corticosteroids). Upon resolution of the reaction, the infusion may be restarted at a slower infusion rate with gradual increase to complete the infusion.

Vaccinations: Prior to initiating SPEVIGO for treatment of GPP, complete all age-appropriate vaccinations according to current immunization guidelines. Avoid use of live vaccines in patients during and for at least 16 weeks after treatment with SPEVIGO. No specific studies have been conducted in SPEVIGO-treated patients who have recently received live viral or live bacterial vaccines.

ADVERSE REACTIONS

Intravenous SPEVIGO for Treatment of GPP Flare (Study Effisayil-1): Most common adverse reactions reported in ≥5% of patients treated with SPEVIGO in the clinical trial were asthenia and fatigue, nausea and vomiting, headache, pruritus and prurigo, infusion site hematoma and bruising, and urinary tract infection (UTI).

Specific Adverse Reactions 

  • Infections: The most frequent adverse reactions that occurred in subjects treated with intravenous SPEVIGO were infections. During the 1-week placebo-controlled period in Study Effisayil-1, infections were reported in 14% of subjects treated with SPEVIGO compared with 6% of subjects treated with placebo. Serious infection (UTI) was reported in 1 subject (3%) in the SPEVIGO group and no subjects in the placebo group. Infections observed through Week 1 in Study Effisayil-1 in subjects treated with SPEVIGO were mild (29%) to moderate (71%). 

  • Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS): Two cases of DRESS were reported in Study Effisayil-1 in subjects with GPP who were treated with intravenous SPEVIGO. RegiSCAR DRESS validation scoring (with the following categories: “no,” “possible,” “probable,” or “definite” DRESS) was applied to the reported cases. Reported cases were assessed as “no DRESS” and “possible DRESS.”

Subcutaneous SPEVIGO for Treatment of GPP When Not Experiencing a Flare (Study Effisayil-2): Regarding the exposure-adjusted incidence rates for subjects on randomized treatment prior to receiving rescue treatment for flare or completing trial without a flare, the rate per 100-patient years for injection site reaction (including erythema, pain, swelling, induration, urticaria, and warmth at the injection site) was 31.6 for the subcutaneous SPEVIGO cohort (600 mg loading dose followed by 300 mg every 4 weeks) vs 12.7 for the placebo cohort. The rate per 100-patient years for UTI was 18 for SPEVIGO vs 0 for placebo. The rate per 100-patient years for pruritus was 8.8 for SPEVIGO vs 0 for placebo. The rate per 100-patient years for arthralgia was 13.3 for SPEVIGO vs 6 for the placebo cohort. There were 3 subjects who discontinued subcutaneous SPEVIGO due to treatment-emergent adverse events of psoriasis compared to no subjects in the placebo cohort who discontinued placebo for any treatment-emergent adverse event.

Safety in Study Effisayil-2 After Flare: In Effisayil-2, subjects who experienced a GPP flare and received at least one dose of an open-label single intravenous 900 mg dose of SPEVIGO were treated with open-label subcutaneous SPEVIGO 300 mg. These subjects (n=19) received subcutaneous dosing at every 12 weeks, which could have been increased to every 4 weeks based on GPPPGA total score or pustulation subscore increased by ≥1 from any previous open-label maintenance visit. The reported safety profile of open-label subcutaneous SPEVIGO use after treatment of GPP flare with open-label intravenous SPEVIGO use was consistent with the safety profiles of use of SPEVIGO from Trial Effisayil-1 and randomized controlled data from Trial Effisayil-2. 

Clinical Development of Spesolimab-sbzo 

  • Guillain-Barre Syndrome (GBS): Among approximately 835 subjects exposed to spesolimab-sbzo during clinical development, GBS was reported in 3 subjects who received various doses of spesolimab-sbzo via various methods of administration in clinical trials for unapproved indications. 

SPECIFIC POPULATIONS

Pediatric Use: The safety and effectiveness of SPEVIGO for the treatment of GPP have been established in pediatric patients 12 years of age and older and weighing at least 40 kg. Use of SPEVIGO for this indication is supported by data from a randomized, placebo-controlled study, which included 6 pediatric subjects 14 to 17 years of age with a history of GPP treated with subcutaneous SPEVIGO (Study Effisayil-2), and evidence from an adequate and well-controlled study of intravenous SPEVIGO in adults with GPP (Study Effisayil-1), with additional pharmacokinetic analyses showing similar drug exposure levels in adults and pediatric subjects 12 years of age and older and weighing 40 kg or more. The safety and effectiveness of SPEVIGO in pediatric patients younger than 12 years of age or in pediatric patients weighing less than 40 kg have not been established. 

CL-SPG-100005 03.19.2024

Please see SPEVIGO Prescribing Information, including Medication Guide.