Spevigo

Subcutaneous Use for Treatment of GPP When Not Experiencing a Flare

• SPEVIGO prefilled syringes are for subcutaneous use for treatment of GPP when not experiencing a flare.
• When using SPEVIGO 300 mg/2 mL prefilled syringe:
  • If the healthcare professional determines that it is appropriate, a patient 12 years of age or older may self-inject or the caregiver may administer the loading dose and the subsequent doses of SPEVIGO after proper training in subcutaneous injection technique. In pediatric patients 12 years of age and older, administer SPEVIGO under the supervision of an adult.
• When using SPEVIGO 150 mg/mL prefilled syringe:
  • If required, the 600 mg subcutaneous loading dose of SPEVIGO is to be administered by a healthcare professional [see Dosage and Administration (2.3)].
  • For subsequent 300 mg doses, if the healthcare professional determines that it is appropriate, a patient 12 years of age or older may self-inject or the caregiver may administer SPEVIGO after proper training in subcutaneous injection technique. In pediatric patients 12 years of age and older, administer SPEVIGO under the supervision of an adult.
• If a patient experiences a GPP flare while receiving subcutaneous SPEVIGO, the GPP flare may be treated with intravenous SPEVIGO [see Dosage and Administration (2.4)].

Storage and Handling

Spesolimab-sbzo, an interleukin-36 receptor antagonist, is a humanized monoclonal IgG1 antibody (mAb) against human IL-36R produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology. Spesolimab-sbzo has a molecular weight of approximately 146 kDa.

SPEVIGO (spesolimab-sbzo) injection is a sterile, preservative-free, colorless to slightly brownish-yellow, clear to slightly opalescent solution supplied in a single-dose prefilled syringe for subcutaneous use. Each 2 mL prefilled syringe contains 300 mg spesolimab-sbzo, arginine hydrochloride (10.6 mg), glacial acetic acid (0.64 mg), polysorbate 20 (0.80 mg), sodium acetate (6.50 mg), sucrose (102.8 mg), and Water for Injection, USP with a pH of 5.2 to 5.8. Each 1 mL prefilled syringe contains 150 mg spesolimab-sbzo, arginine hydrochloride (5.3 mg), glacial acetic acid (0.32 mg), polysorbate 20 (0.40 mg), sodium acetate (3.25 mg), sucrose (51.4 mg), and Water for Injection, USP with a pH of 5.2 to 5.8.

SPEVIGO (spesolimab-sbzo) injection is a sterile, preservative-free, colorless to slightly brownish-yellow, clear to slightly opalescent solution supplied in a single-dose vial for intravenous use. Each 7.5 mL vial contains 450 mg spesolimab-sbzo, arginine hydrochloride (39.5 mg), glacial acetic acid (2.4 mg), polysorbate 20 (3.0 mg), sodium acetate (24.5 mg), sucrose (386 mg), and Water for Injection, USP with a pH of 5.2 to 5.8.

SPEVIGO may increase the risk of infections. During the one-week placebo-controlled period in the Effisayil-1 trial, infections were reported in 14% of subjects treated with SPEVIGO compared with 6% of subjects treated with placebo [see Adverse Reactions (6.1)].

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.

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.

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 [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14)].

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.

There were 2 (6%) intravenous SPEVIGO-treated subjects 65 to 74 years of age and no subjects 75 years of age or older in Study Effisayil-1. There were 6 (7%) subcutaneous SPEVIGO-treated subjects 65 to 74 years of age and 1 (1%) subject 75 years of age in Study Effisayil-2. Clinical studies of SPEVIGO did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of spesolimab-sbzo or of other spesolimab products.

In subjects with GPP treated with intravenous SPEVIGO in Study Effisayil-1, ADAs formed with a median onset of 2.3 weeks. Following administration of 900 mg intravenous SPEVIGO, (12/50) 24% of subjects had a maximum ADA titer greater than 4000 and were neutralizing antibody (Nab)-positive by the end of the study (Weeks 12 to 17). In Study Effisayil-2, ADAs formed with a median onset of 8 weeks. Following administration of a 600 mg subcutaneous LD of SPEVIGO followed by 300 mg every 4 weeks for a total duration of 48 weeks, 24% of subjects had a maximum ADA titer greater than 4000 and were Nab-positive.

In Study Effisayil-1 following intravenous SPEVIGO, females appeared to have higher immunogenicity response; the percentage of subjects with ADA titer greater than 4000 was 30% in females, and 12% in males, respectively. In Study Effisayil-2 following administration of subcutaneous SPEVIGO, the data on immunogenicity response in males versus females were inconclusive.

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) and anaphylaxis [see Warnings and Precautions (5.3) and Adverse Reactions (6)].

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Infections [see Warnings and Precautions (5.1)]
• Hypersensitivity and Infusion-Related Reactions [see Warnings and Precautions (5.3)]

This Instructions for Use contains information on how to inject SPEVIGO.

Read both sides of this Instructions for Use before you use SPEVIGO for the first time and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your or your child's medical condition or treatment. Your healthcare provider should show you or your child the right way to inject SPEVIGO before you try to inject yourself or your child for the first time. In children 12 years of age and older, SPEVIGO should be given under the supervision of an adult.

SPEVIGO is for one-time use only. Do not reuse the prefilled syringes.

Your healthcare provider has prescribed a dose of SPEVIGO for you or your child that requires 2 injections (2 prefilled syringes) to deliver a complete dose.

You must inject the contents of both SPEVIGO prefilled syringes that come in the carton to deliver the complete dose.

Getting to know SPEVIGO:

SPEVIGO comes in a prefilled syringe with a safety cover. The needle is pulled back into the safety cover after injection.

Guide to parts:

The figure below shows SPEVIGO before use, and after use with the activated safety cover.

Important information you need to know before injecting SPEVIGO:

• You must inject the contents of both SPEVIGO prefilled syringes to deliver a complete dose.
• Inspect the SPEVIGO carton to be sure that you have the correct medicine, 2 prefilled syringes for your or your child's prescribed dose, for any damage, and the expiration date (EXP).
• Do not use SPEVIGO if the liquid is cloudy or contains flakes or large or colored particles.
• Do not use SPEVIGO if the expiration date (EXP) has passed.
• Do not use SPEVIGO if the prefilled syringe has been dropped.
• Do not remove the cap until you are ready to inject.
• Inject SPEVIGO under the skin (subcutaneous injection) in either the upper thighs or stomach-area (abdomen). Do not inject SPEVIGO into any other area of the body.

Storing SPEVIGO:

Keep SPEVIGO and all medicines out of the reach of children.

Manufactured by:

Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877 USA

US License Number 2006

Licensed from: Boehringer Ingelheim International GmbH, Ingelheim, Germany

SPEVIGO is a registered trademark of and used under license from Boehringer Ingelheim International GmbH.

Copyright © 2025 Boehringer Ingelheim International GmbH ALL RIGHTS RESERVED

COL12534BE292025

For more information about SPEVIGO, including current prescribing information and Medication Guide, go to www.SPEVIGO.com, scan the code below, or call Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: 05/2025

The pharmacodynamics of SPEVIGO in the treatment of patients with GPP have not been fully characterized.

A population pharmacokinetic model was developed based on data collected from healthy subjects, patients with GPP, and patients with other diseases. After a single intravenous dose of 900 mg of SPEVIGO, the population PK model-estimated AUC_0-∞ (95% CI) and C_max (95% CI) in a typical anti-drug antibody (ADA)-negative patient with GPP were 4750 (4510, 4970) mcg∙day/mL and 238 (218, 256) mcg/mL, respectively. After subcutaneous SPEVIGO 600 mg LD followed by 300 mg every 4 weeks, the mean steady-state trough concentration ranged from 33.4 mcg/mL to 42.3 mcg/mL.

When administered intravenously, spesolimab-sbzo AUC increased dose-proportionally from 0.3 to 20 mg/kg, and CL and terminal half-life were independent of dose. Following subcutaneous single dose administration, spesolimab-sbzo exposure increased slightly more than dose-proportionally across the dose range of 150 mg to 600 mg due to increased bioavailability at higher doses.

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.

Spesolimab-sbzo is a humanized monoclonal immunoglobulin G1 antibody that inhibits interleukin-36 (IL-36) signaling by specifically binding to the IL36R. Binding of spesolimab-sbzo to IL36R prevents the subsequent activation of IL36R by its ligands (IL-36 α, β and γ) and downstream activation of pro-inflammatory and pro-fibrotic pathways. The precise mechanism linking reduced IL36R activity and the treatment of flares of GPP is unclear.

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.

• Infections: SPEVIGO may increase the risk of infections. Treatment with SPEVIGO is not recommended during any clinically important active infection. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur during or after treatment. If a clinically important active infection develops, discontinue SPEVIGO until the infection resolves or is adequately treated. (5.1)
• Risk of Tuberculosis (TB): Evaluate patients for TB prior to initiating treatment with SPEVIGO. (5.2)
• Hypersensitivity and Infusion-Related Reactions: Hypersensitivity reactions, including anaphylaxis and drug reaction with eosinophilia and systemic symptoms (DRESS), and infusion-related reactions may occur. Discontinue SPEVIGO immediately and initiate appropriate treatment if a serious hypersensitivity reaction occurs. (5.3)
• Vaccinations: Avoid use of live vaccines during and for at least 16 weeks after treatment with SPEVIGO. (5.4)

Subcutaneous Dosage for Treatment of GPP When Not Experiencing a Flare

Administer a subcutaneous loading dose of 600 mg, followed by 300 mg subcutaneously 4 weeks later and every 4 weeks thereafter. (2.3)

• Subcutaneous Use After Intravenous SPEVIGO for Treatment of GPP Flare: Four weeks after treatment with intravenous SPEVIGO, initiate or reinitiate subcutaneous SPEVIGO at a dose of 300 mg administered every 4 weeks. A loading dose is not required following treatment of a GPP flare with intravenous SPEVIGO. (2.3)
• See full prescribing information for preparation and administration instructions. (2.2, 2.5)

Intravenous Dosage for Treatment of GPP Flare

• Must be diluted before intravenous use. Administer as a single 900 mg dose by intravenous infusion over 90 minutes. If flare symptoms persist, may administer an additional intravenous 900 mg dose one week after the initial dose. (2.4)
• See full prescribing information for preparation and administration instructions and storage of the diluted solution. (2.2, 2.5)

SPEVIGO is a colorless to slightly brownish-yellow, clear to slightly opalescent solution available as:

The following adverse reactions have been identified during postapproval use of SPEVIGO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders: Immediate systemic hypersensitivity reactions, including anaphylaxis.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Parenteral drug products should be inspected visually for particulate matter and discoloration, whenever solution and container permits. SPEVIGO is a colorless to slightly brownish-yellow, clear to slightly opalescent solution. Do not use if the solution is cloudy, discolored, or contains large or colored particulates.

NDC 0597-0620-20

ATTENTION PHARMACIST:

This Entire Carton is to be

Dispensed as a Unit with

Enclosed Medication Guide.

Spevigo^®

(spesolimab-sbzo)

Injection

150 mg/mL per Syringe

For Subcutaneous Use Only

For a complete 300 mg dose, two

150 mg syringes are required.

Inject one syringe after the other.

TWO 150 mg Single-Dose Prefilled Syringes

Rx only

Boehringer

Ingelheim

Serious hypersensitivity reactions, including anaphylaxis and delayed reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported during and following administration of SPEVIGO. These reactions can occur with the first dose or subsequent doses [see Adverse Reactions (6.1)].

SPEVIGO is contraindicated in patients with severe or life-threatening hypersensitivity to spesolimab-sbzo or to any of the excipients in SPEVIGO. 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 (e.g., 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.

NDC 0597-0035-10

Rx only

DISPENSE WITH ENCLOSED MEDICATION GUIDE

Spevigo^®

(spesolimab-sbzo)

Injection

450 mg/7.5 mL per vial

(60 mg/mL)

For Intravenous Infusion after Dilution

Discard Unused Portion

Prepare both vials in carton for

a complete dose of 900 mg

Contents: contains TWO - 450 mg/7.5 mL single-dose vials

Boehringer

Ingelheim

NDC 0597-7705-41

ATTENTION PHARMACIST:

This Entire Carton is to be

Dispensed as a Unit with

Enclosed Medication Guide.

Spevigo^®

(spesolimab-sbzo) injection

300 mg/2 mL

(150 mg/mL)

For Subcutaneous Use Only

1 Single-Dose Prefilled Syringe

Rx only

Boehringer

Ingelheim

Evaluate patients for active or latent tuberculosis (TB) infection. SPEVIGO initiation is not recommended in patients with active TB infection. Consider initiating treatment of latent TB prior to initiation of SPEVIGO [see Warnings and Precautions (5.2)].

Complete all age-appropriate vaccinations according to current immunization guidelines prior to initiating SPEVIGO for treatment of GPP [see Warnings and Precautions (5.4)].

Carcinogenicity and mutagenicity studies have not been conducted with spesolimab-sbzo.

No adverse effects on fertility were observed in male or female mice that were intravenously administered a surrogate antibody to IL36R at doses up to 50 mg/kg twice weekly.

The recommended dosage of SPEVIGO for treatment of GPP flare in adults and pediatric patients 12 years of age and older and weighing at least 40 kg is a single 900 mg dose administered by intravenous infusion over 90 minutes.

If GPP flare symptoms persist, an additional intravenous 900 mg dose (over 90 minutes) may be administered one week after the initial dose.

The recommended dosage of SPEVIGO for treatment of GPP when not experiencing a flare in adults and pediatric patients 12 years of age and older and weighing at least 40 kg is a loading dose of 600 mg followed by 300 mg administered subcutaneously 4 weeks later and every 4 weeks thereafter.

Subcutaneous Use for Treatment of GPP When Not Experiencing a Flare

• SPEVIGO prefilled syringes are for subcutaneous use for treatment of GPP when not experiencing a flare.
• When using SPEVIGO 300 mg/2 mL prefilled syringe:
  • If the healthcare professional determines that it is appropriate, a patient 12 years of age or older may self-inject or the caregiver may administer the loading dose and the subsequent doses of SPEVIGO after proper training in subcutaneous injection technique. In pediatric patients 12 years of age and older, administer SPEVIGO under the supervision of an adult.
• When using SPEVIGO 150 mg/mL prefilled syringe:
  • If required, the 600 mg subcutaneous loading dose of SPEVIGO is to be administered by a healthcare professional [see Dosage and Administration (2.3)].
  • For subsequent 300 mg doses, if the healthcare professional determines that it is appropriate, a patient 12 years of age or older may self-inject or the caregiver may administer SPEVIGO after proper training in subcutaneous injection technique. In pediatric patients 12 years of age and older, administer SPEVIGO under the supervision of an adult.
• If a patient experiences a GPP flare while receiving subcutaneous SPEVIGO, the GPP flare may be treated with intravenous SPEVIGO [see Dosage and Administration (2.4)].

Storage and Handling

Spesolimab-sbzo, an interleukin-36 receptor antagonist, is a humanized monoclonal IgG1 antibody (mAb) against human IL-36R produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology. Spesolimab-sbzo has a molecular weight of approximately 146 kDa.

SPEVIGO (spesolimab-sbzo) injection is a sterile, preservative-free, colorless to slightly brownish-yellow, clear to slightly opalescent solution supplied in a single-dose prefilled syringe for subcutaneous use. Each 2 mL prefilled syringe contains 300 mg spesolimab-sbzo, arginine hydrochloride (10.6 mg), glacial acetic acid (0.64 mg), polysorbate 20 (0.80 mg), sodium acetate (6.50 mg), sucrose (102.8 mg), and Water for Injection, USP with a pH of 5.2 to 5.8. Each 1 mL prefilled syringe contains 150 mg spesolimab-sbzo, arginine hydrochloride (5.3 mg), glacial acetic acid (0.32 mg), polysorbate 20 (0.40 mg), sodium acetate (3.25 mg), sucrose (51.4 mg), and Water for Injection, USP with a pH of 5.2 to 5.8.

SPEVIGO (spesolimab-sbzo) injection is a sterile, preservative-free, colorless to slightly brownish-yellow, clear to slightly opalescent solution supplied in a single-dose vial for intravenous use. Each 7.5 mL vial contains 450 mg spesolimab-sbzo, arginine hydrochloride (39.5 mg), glacial acetic acid (2.4 mg), polysorbate 20 (3.0 mg), sodium acetate (24.5 mg), sucrose (386 mg), and Water for Injection, USP with a pH of 5.2 to 5.8.

SPEVIGO may increase the risk of infections. During the one-week placebo-controlled period in the Effisayil-1 trial, infections were reported in 14% of subjects treated with SPEVIGO compared with 6% of subjects treated with placebo [see Adverse Reactions (6.1)].

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.

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.

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 [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14)].

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.

There were 2 (6%) intravenous SPEVIGO-treated subjects 65 to 74 years of age and no subjects 75 years of age or older in Study Effisayil-1. There were 6 (7%) subcutaneous SPEVIGO-treated subjects 65 to 74 years of age and 1 (1%) subject 75 years of age in Study Effisayil-2. Clinical studies of SPEVIGO did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of spesolimab-sbzo or of other spesolimab products.

In subjects with GPP treated with intravenous SPEVIGO in Study Effisayil-1, ADAs formed with a median onset of 2.3 weeks. Following administration of 900 mg intravenous SPEVIGO, (12/50) 24% of subjects had a maximum ADA titer greater than 4000 and were neutralizing antibody (Nab)-positive by the end of the study (Weeks 12 to 17). In Study Effisayil-2, ADAs formed with a median onset of 8 weeks. Following administration of a 600 mg subcutaneous LD of SPEVIGO followed by 300 mg every 4 weeks for a total duration of 48 weeks, 24% of subjects had a maximum ADA titer greater than 4000 and were Nab-positive.

In Study Effisayil-1 following intravenous SPEVIGO, females appeared to have higher immunogenicity response; the percentage of subjects with ADA titer greater than 4000 was 30% in females, and 12% in males, respectively. In Study Effisayil-2 following administration of subcutaneous SPEVIGO, the data on immunogenicity response in males versus females were inconclusive.

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) and anaphylaxis [see Warnings and Precautions (5.3) and Adverse Reactions (6)].

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Infections [see Warnings and Precautions (5.1)]
• Hypersensitivity and Infusion-Related Reactions [see Warnings and Precautions (5.3)]

This Instructions for Use contains information on how to inject SPEVIGO.

Read both sides of this Instructions for Use before you use SPEVIGO for the first time and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your or your child's medical condition or treatment. Your healthcare provider should show you or your child the right way to inject SPEVIGO before you try to inject yourself or your child for the first time. In children 12 years of age and older, SPEVIGO should be given under the supervision of an adult.

SPEVIGO is for one-time use only. Do not reuse the prefilled syringes.

Your healthcare provider has prescribed a dose of SPEVIGO for you or your child that requires 2 injections (2 prefilled syringes) to deliver a complete dose.

You must inject the contents of both SPEVIGO prefilled syringes that come in the carton to deliver the complete dose.

Getting to know SPEVIGO:

SPEVIGO comes in a prefilled syringe with a safety cover. The needle is pulled back into the safety cover after injection.

Guide to parts:

The figure below shows SPEVIGO before use, and after use with the activated safety cover.

Important information you need to know before injecting SPEVIGO:

• You must inject the contents of both SPEVIGO prefilled syringes to deliver a complete dose.
• Inspect the SPEVIGO carton to be sure that you have the correct medicine, 2 prefilled syringes for your or your child's prescribed dose, for any damage, and the expiration date (EXP).
• Do not use SPEVIGO if the liquid is cloudy or contains flakes or large or colored particles.
• Do not use SPEVIGO if the expiration date (EXP) has passed.
• Do not use SPEVIGO if the prefilled syringe has been dropped.
• Do not remove the cap until you are ready to inject.
• Inject SPEVIGO under the skin (subcutaneous injection) in either the upper thighs or stomach-area (abdomen). Do not inject SPEVIGO into any other area of the body.

Storing SPEVIGO:

Keep SPEVIGO and all medicines out of the reach of children.

Manufactured by:

Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877 USA

US License Number 2006

Licensed from: Boehringer Ingelheim International GmbH, Ingelheim, Germany

SPEVIGO is a registered trademark of and used under license from Boehringer Ingelheim International GmbH.

Copyright © 2025 Boehringer Ingelheim International GmbH ALL RIGHTS RESERVED

COL12534BE292025

For more information about SPEVIGO, including current prescribing information and Medication Guide, go to www.SPEVIGO.com, scan the code below, or call Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Revised: 05/2025

The pharmacodynamics of SPEVIGO in the treatment of patients with GPP have not been fully characterized.

A population pharmacokinetic model was developed based on data collected from healthy subjects, patients with GPP, and patients with other diseases. After a single intravenous dose of 900 mg of SPEVIGO, the population PK model-estimated AUC_0-∞ (95% CI) and C_max (95% CI) in a typical anti-drug antibody (ADA)-negative patient with GPP were 4750 (4510, 4970) mcg∙day/mL and 238 (218, 256) mcg/mL, respectively. After subcutaneous SPEVIGO 600 mg LD followed by 300 mg every 4 weeks, the mean steady-state trough concentration ranged from 33.4 mcg/mL to 42.3 mcg/mL.

When administered intravenously, spesolimab-sbzo AUC increased dose-proportionally from 0.3 to 20 mg/kg, and CL and terminal half-life were independent of dose. Following subcutaneous single dose administration, spesolimab-sbzo exposure increased slightly more than dose-proportionally across the dose range of 150 mg to 600 mg due to increased bioavailability at higher doses.

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.

Spesolimab-sbzo is a humanized monoclonal immunoglobulin G1 antibody that inhibits interleukin-36 (IL-36) signaling by specifically binding to the IL36R. Binding of spesolimab-sbzo to IL36R prevents the subsequent activation of IL36R by its ligands (IL-36 α, β and γ) and downstream activation of pro-inflammatory and pro-fibrotic pathways. The precise mechanism linking reduced IL36R activity and the treatment of flares of GPP is unclear.

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.

• Infections: SPEVIGO may increase the risk of infections. Treatment with SPEVIGO is not recommended during any clinically important active infection. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur during or after treatment. If a clinically important active infection develops, discontinue SPEVIGO until the infection resolves or is adequately treated. (5.1)
• Risk of Tuberculosis (TB): Evaluate patients for TB prior to initiating treatment with SPEVIGO. (5.2)
• Hypersensitivity and Infusion-Related Reactions: Hypersensitivity reactions, including anaphylaxis and drug reaction with eosinophilia and systemic symptoms (DRESS), and infusion-related reactions may occur. Discontinue SPEVIGO immediately and initiate appropriate treatment if a serious hypersensitivity reaction occurs. (5.3)
• Vaccinations: Avoid use of live vaccines during and for at least 16 weeks after treatment with SPEVIGO. (5.4)

Subcutaneous Dosage for Treatment of GPP When Not Experiencing a Flare

Administer a subcutaneous loading dose of 600 mg, followed by 300 mg subcutaneously 4 weeks later and every 4 weeks thereafter. (2.3)

• Subcutaneous Use After Intravenous SPEVIGO for Treatment of GPP Flare: Four weeks after treatment with intravenous SPEVIGO, initiate or reinitiate subcutaneous SPEVIGO at a dose of 300 mg administered every 4 weeks. A loading dose is not required following treatment of a GPP flare with intravenous SPEVIGO. (2.3)
• See full prescribing information for preparation and administration instructions. (2.2, 2.5)

Intravenous Dosage for Treatment of GPP Flare

• Must be diluted before intravenous use. Administer as a single 900 mg dose by intravenous infusion over 90 minutes. If flare symptoms persist, may administer an additional intravenous 900 mg dose one week after the initial dose. (2.4)
• See full prescribing information for preparation and administration instructions and storage of the diluted solution. (2.2, 2.5)

SPEVIGO is a colorless to slightly brownish-yellow, clear to slightly opalescent solution available as:

The following adverse reactions have been identified during postapproval use of SPEVIGO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders: Immediate systemic hypersensitivity reactions, including anaphylaxis.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

Parenteral drug products should be inspected visually for particulate matter and discoloration, whenever solution and container permits. SPEVIGO is a colorless to slightly brownish-yellow, clear to slightly opalescent solution. Do not use if the solution is cloudy, discolored, or contains large or colored particulates.

NDC 0597-0620-20

ATTENTION PHARMACIST:

This Entire Carton is to be

Dispensed as a Unit with

Enclosed Medication Guide.

Spevigo^®

(spesolimab-sbzo)

Injection

150 mg/mL per Syringe

For Subcutaneous Use Only

For a complete 300 mg dose, two

150 mg syringes are required.

Inject one syringe after the other.

TWO 150 mg Single-Dose Prefilled Syringes

Rx only

Boehringer

Ingelheim

Serious hypersensitivity reactions, including anaphylaxis and delayed reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported during and following administration of SPEVIGO. These reactions can occur with the first dose or subsequent doses [see Adverse Reactions (6.1)].

SPEVIGO is contraindicated in patients with severe or life-threatening hypersensitivity to spesolimab-sbzo or to any of the excipients in SPEVIGO. 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 (e.g., 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.

NDC 0597-0035-10

Rx only

DISPENSE WITH ENCLOSED MEDICATION GUIDE

Spevigo^®

(spesolimab-sbzo)

Injection

450 mg/7.5 mL per vial

(60 mg/mL)

For Intravenous Infusion after Dilution

Discard Unused Portion

Prepare both vials in carton for

a complete dose of 900 mg

Contents: contains TWO - 450 mg/7.5 mL single-dose vials

Boehringer

Ingelheim

NDC 0597-7705-41

ATTENTION PHARMACIST:

This Entire Carton is to be

Dispensed as a Unit with

Enclosed Medication Guide.

Spevigo^®

(spesolimab-sbzo) injection

300 mg/2 mL

(150 mg/mL)

For Subcutaneous Use Only

1 Single-Dose Prefilled Syringe

Rx only

Boehringer

Ingelheim

Evaluate patients for active or latent tuberculosis (TB) infection. SPEVIGO initiation is not recommended in patients with active TB infection. Consider initiating treatment of latent TB prior to initiation of SPEVIGO [see Warnings and Precautions (5.2)].

Complete all age-appropriate vaccinations according to current immunization guidelines prior to initiating SPEVIGO for treatment of GPP [see Warnings and Precautions (5.4)].

Carcinogenicity and mutagenicity studies have not been conducted with spesolimab-sbzo.

No adverse effects on fertility were observed in male or female mice that were intravenously administered a surrogate antibody to IL36R at doses up to 50 mg/kg twice weekly.

The recommended dosage of SPEVIGO for treatment of GPP flare in adults and pediatric patients 12 years of age and older and weighing at least 40 kg is a single 900 mg dose administered by intravenous infusion over 90 minutes.

If GPP flare symptoms persist, an additional intravenous 900 mg dose (over 90 minutes) may be administered one week after the initial dose.

The recommended dosage of SPEVIGO for treatment of GPP when not experiencing a flare in adults and pediatric patients 12 years of age and older and weighing at least 40 kg is a loading dose of 600 mg followed by 300 mg administered subcutaneously 4 weeks later and every 4 weeks thereafter.