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Dragon Breathing Out Flowers

SPEVIGO IV 
(intravenous) was 
evaluated in the 
Effisayil® 1 trial1,2

The EFFISAYIL 1 trial was a multicenter, randomized, double-blind, placebo-controlled trial of SPEVIGO IV in patients with GPP experiencing a flare1,2

Spevigo® Effisayil 1 Study Design
  • *
    Patients must have discontinued biologics, retinoids, methotrexate, and/or cyclosporine before receiving their first dose of SPEVIGO IV or placebo.2
  • †
    Persistent flare defined as ≥2 GPPPGA total score and ≥2 GPPPGA pustulation subscore.2
  • ‡
    Patients who received other medications for GPP during Week 1 were not eligible for SPEVIGO IV at Day 8.3
  • §
    Defined as a ≥2-point increase in GPPPGA total score and GPPPGA pustulation subscore after achieving clinical response (GPPPGA total score of 0 or 1).2
  • ||
    After Day 8, patients with a new flare (defined as ≥2-point increase in GPPPGA total score and pustulation subscore) could receive OL SPEVIGO IV if a GPPPGA total score of 0 or 1 had been reached with SPEVIGO IV or placebo before.2
  • At the end of Week 1, 2 patients on SPEVIGO IV and 1 patient on placebo had received ≥1 other treatment for GPP therapy. From Day 8 to the end of the trial, 4 patients in each arm received ≥1 other treatment for GPP therapy.2

Patients who did not require rescue treatment with OL SPEVIGO IV were followed until Week 12 (EoT) before entering the open-label extension. Patients who received rescue 
treatment with OL SPEVIGO IV between Weeks 2 and 6 were followed until Week 12 (EoT) before entering the open-label extension. Week 12 was considered EoT for patients who qualified for the open-label extension. Patients who did not qualify to enter the open-label extension were to be followed (EoT Weeks 16-28) after the last dose of medication given during the trial.3

After Day 8 to Week 12: Only 1 rescue dose with OL SPEVIGO IV was permitted if a patient who previously achieved GPPPGA 0/1 to initial treatment, either with SPEVIGO IV 
or placebo at Day 1, or escape medication or OL SPEVIGO IV at Day 8, experienced a recurrence of a GPP flare. Subsequent flares were treated with other therapies of 
physician’s choice.2

EoT=end of trial; GPP=generalized pustular psoriasis; GPPPGA=Generalized Pustular Psoriasis Physician Global Assessment; IV=intravenous; OL=open label.

Endpoint summary

Spevigo® Effisayil 1 Study Design Endpoint Summary

FACIT=Functional Assessment of Chronic Illness Therapy; GPPASI=Psoriasis Area and Severity Index for Generalized Pustular Psoriasis; PSS=Psoriasis Symptom Scale; VAS=Visual Analogue Scale.

Patients 18 to 75 years of age were included if they experienced a generalized pustular psoriasis
(GPP) flare of moderate to severe intensity prior to randomization, defined in the trial as:

  • A Generalized Pustular Psoriasis Physician Global Assessment (GPPPGA) total score of ≥3
  • New appearance or worsening of existing pustules
  • A GPPPGA pustulation subscore of ≥2
  • ≥5% body surface area covered with erythema and the presence of pustules

Patients were excluded if they presented with:

  • Synovitis, acne, pustulosis, hyperostosis, osteitis syndrome
  • Plaque psoriasis without pustules or with pustules restricted to psoriatic plaques
  • Drug-triggered acute generalized exanthematous pustulosis
  • Immediate, life-threatening flare of GPP flare requiring intensive care treatment
  • Dose escalation of their maintenance treatment with cyclosporine, retinoids, or methotrexate within 2 weeks prior to randomization
  • Treatment with any drug, including biologics and systemic drugs, considered likely to interfere with the safe conduct of the study or any prior exposure to an interleukin-36 receptor inhibitor

The Generalized Pustular Psoriasis Physician Global Assessment (GPPPGA) is used to evaluate flare symptoms and treatment efficacy3

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, scaling, and erythema, 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 efficacy3 

GPPPGA Score Card

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 skin3

  • *
    Flare control defined as GPPPGA total score ≤1 and was reported for the 12-week study period.2
  • †
    To receive a score of 0 or 1, the patient should be afebrile, in addition to skin presentation requirements.3

In EFFISAYIL 1, SPEVIGO IV was evaluated across various demographics and baseline characteristics2

Spevigo® Characteristics Evaluation

This study did not include a sufficient number of subjects to determine if there are differences in response according to the various baseline demographics and characteristics.1

  • *
    Race was reported by the patient.2
  • †
    A total of 52 patients were included: 34 in the SPEVIGO arm and 18 in the placebo arm. Five patients had missing values at baseline.2

CRP=C-reactive protein; SD=standard deviation.

References

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

  2. 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

  3. 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

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.