ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following adverse reactions are discussed in greater detail in other sections of the labeling:Infections [see Warnings and Precautions (5.1)] Infections [see Warnings and Precautions (5.1)] Most common adverse reactions (>=5%) are asthenia and fatigue, nausea and vomiting, headache, pruritus and prurigo, infusion site hematoma and bruising, and urinary tract infection. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at (800) 542-6257 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.SPEVIGO was studied in Study Effisayil-1, randomized, double-blind, placebo-controlled trial comparing single intravenous 900 mg dose of SPEVIGO (n=35) with placebo (n=18) in subjects with generalized pustular psoriasis flare. Subjects in either treatment group who continued to experience flare symptoms at Week were eligible to receive single open-label intravenous dose of 900 mg of SPEVIGO (second dose and first dose for subjects in the SPEVIGO and placebo groups, respectively). At Week 1, 12 (34%) subjects and 15 subjects (83%) in the SPEVIGO and placebo groups, respectively, received open-label SPEVIGO. After Week to Week 12, subjects in either treatment group whose GPP flare reoccurred after achieving clinical response were eligible to receive single open-label rescue intravenous dose of 900 mg of SPEVIGO, with maximum of total doses of SPEVIGO throughout the study. Six subjects received single open-label rescue dose of SPEVIGO. Thirty-six subjects received dose of SPEVIGO, 13 subjects received doses of SPEVIGO, and subjects received doses of SPEVIGO throughout the study [see Clinical Studies (14)].Subjects ranged in age from 21 to 69 years (mean age of 43 years); 45% were White and 55% were Asian; and 68% were female.Table summarizes selected adverse reactions that occurred at rate of at least 1% and at higher rate in the SPEVIGO group than in the placebo group through Week 1.Table 1Selected Adverse Reactions Occurring in >=1% of the SPEVIGO Group and More Frequently than in the Placebo Group through Week (Study Effisayil-1)Adverse ReactionSPEVIGO = 35 (%)Placebo = 18 (%)Asthenia and Fatigue3 (9)0Nausea and Vomiting3 (9)1 (6)Headache3 (9)1 (6)Pruritus and prurigo2 (6)0Infusion site hematoma and bruising2 (6)0Urinary tract infection2 (6)0Bacteremia1 (3)0Bacteriuria1 (3)0Cellulitis1 (3)0Herpes dermatitis and oral herpes1 (3)0Upper respiratory tract infection1 (3)0Dyspnea (3)0Eye edema1 (3)0Urticaria (3)0. Specific Adverse Reactions. InfectionsThe most frequent adverse reactions that occurred in subjects treated with 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 (urinary tract infection) was reported in subject (3%) treated with SPEVIGO and no subjects treated with placebo. Infections observed through Week 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 spesolimab-sbzo. 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.. Safety through Week 12 and 17In Study Effisayil-1, additional adverse reactions that occurred through Week 12 in subjects treated with single dose of randomized SPEVIGO were mild to moderate infections: device-related infection (3%), subcutaneous abscess (3%), furuncle (3%), and influenza (3%).Additional adverse reactions that occurred through Week 17 in subjects treated with single dose of open-label SPEVIGO at Week (second dose and first dose for subjects in the SPEVIGO and placebo groups, respectively) were mild to moderate infections: otitis externa (7%), vulvovaginal candidiasis (4%), vulvovaginal mycotic infection (4%), and latent tuberculosis (4%), diarrhea (11%), and gastritis (4%). No new adverse reactions were identified for up to 16 weeks in subjects treated with single dose of open-label rescue SPEVIGO from Week to Week 12 (range 1-3 total doses).. Clinical Development. Guillain-Barre syndromeAmong approximately 750 subjects exposed to spesolimab-sbzo during clinical development, Guillain-Barre syndrome (GBS) was reported in subjects who received various doses of spesolimab-sbzo via various methods of administration in clinical trials for unapproved indications.. Injection Site ReactionsDuring clinical development, injection site reactions (including injection site erythema, injection site swelling, injection site pain, injection site induration, and injection site warmth) occurred with spesolimab-sbzo.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Spesolimab-sbzo is 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 cognate ligands (IL-36 and 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.. 12.2 Pharmacodynamics. The pharmacodynamics of SPEVIGO in the treatment of patients with GPP have not been fully characterized.. 12.3 Pharmacokinetics. population pharmacokinetic model was developed based on data collected from healthy subjects, patients with GPP, and patients with other diseases. After single intravenous dose of 900 mg of SPEVIGO, the population PK model-estimated AUC0- (95% CI) and Cmax (95% CI) in typical anti-drug antibody (ADA)-negative patient with GPP were 4750 (4510, 4970) mcgday/mL and 238 (218, 256) mcg/mL, respectively.Spesolimab-sbzo AUC increased dose-proportionally from 0.3 to 20 mg/kg, and CL and terminal half-life were independent of dose.. DistributionBased on the population pharmacokinetic analysis, the typical total volume of distribution at steady state was 6.4 L.. Elimination. MetabolismThe metabolic pathway of spesolimab-sbzo has not been characterized. As humanized IgG1 monoclonal antibody, spesolimab-sbzo is expected to be degraded into small peptides and amino acids via catabolic pathways in manner similar to endogenous IgG.. ExcretionIn the linear dose range (0.3 to 20 mg/kg), based on the population PK model, spesolimab-sbzo clearance (95% CI) in typical GPP patient without ADA, weighing 70 kg was 0.184 (0.175, 0.194) L/day. The terminal half-life was 25.5 (24.4, 26.3) days.. Specific Populations. Age, Gender, and RaceBased on population pharmacokinetic analyses, age, gender, and race did not have an effect on the pharmacokinetics of spesolimab-sbzo.. Hepatic and Renal ImpairmentAs monoclonal antibody, spesolimab-sbzo is not expected to undergo hepatic or renal elimination. No formal study of the effect of hepatic or renal impairment on the pharmacokinetics of spesolimab-sbzo was conducted.. Body WeightSpesolimab-sbzo concentrations were lower in subjects with higher body weight. The clinical impact of body weight on spesolimab-sbzo plasma concentrations is unknown.. Drug Interaction StudiesNo formal drug interactions studies have been conducted with spesolimab-sbzo.. 12.6 Immunogenicity. 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 SPEVIGO in Effisayil-1, ADAs formed with median onset of 2.3 weeks. Following administration of 900 mg intravenous SPEVIGO, (12/50) 24% of subjects had maximum ADA titer greater than 4000 and were neutralizing antibody-positive by the end of the trial (Weeks 12 to 17). 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.. Anti-Drug Antibody Effects on PharmacokineticsIn subjects with ADA titers below 4000, there was no apparent impact on spesolimab-sbzo pharmacokinetics. In most subjects with ADA titer values greater than 4000, plasma spesolimab-sbzo concentrations were significantly reduced after reaching this ADA titer.There are limited data on the impact of ADAs on safety and efficacy upon retreatment as the majority of subjects did not experience subsequent, new flare in an open-label extension trial.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. randomized, double-blind, placebo-controlled study (Study Effisayil-1) [NCT03782792] was conducted to evaluate the clinical efficacy and safety of SPEVIGO in adult subjects with flares of generalized pustular psoriasis (GPP). Subjects were randomized if they had flare of GPP of moderate-to-severe intensity, as defined by:A Generalized Pustular Psoriasis Physician Global Assessment (GPPPGA) total score of at least (moderate) [the total GPPPGA score ranges from (clear) to (severe)],The presence of fresh pustules (new appearance or worsening of pustules),GPPPGA pustulation sub score of at least (mild), andAt least 5% of body surface area covered with erythema and the presence of pustules.Subjects were required to discontinue systemic and topical therapy for GPP prior to receiving study drug.A total of 53 subjects were randomized (2:1) to receive single intravenous dose of 900 mg SPEVIGO (N=35) or placebo (N=18) (administered over 90 minutes) during the double-blind portion of the study.The study population consisted of 32% men and 68% women. The mean age was 43 years (range: 21 to 69 years); 55% of subjects were Asian and 45% were White. Most subjects included in the study had GPPPGA pustulation sub score of (43%) or (36%), and subjects had GPPPGA total score of (81%) or (19%). In this study, 25% of subjects had been previously treated with biologic therapy for GPP. At baseline acute flare, of the subjects with white blood cell count (WBC) assessments, 45% and 31% of subjects in the SPEVIGO and placebo groups, respectively, had (WBC) >12 109/L. Seventeen percent and 11% of subjects in the SPEVIGO and placebo groups, respectively, had temperature >38 Celsius. Of the subjects with WBC assessments, 12% and 6% of subjects in the SPEVIGO and placebo groups, respectively, had both WBC >12 109/L and temperature >38 Celsius [see Adverse Reactions (6.1)]. The primary endpoint of the study was the proportion of subjects with GPPPGA pustulation sub score of (indicating no visible pustules) at Week after treatment. The results of the primary endpoint are presented in Table 2.Table 2GPPPGA Pustulation Sub Score at Week in Study Effisayil-1SPEVIGO (N=35)Placebo (N=18)GPPPGA Generalized Pustular Psoriasis Physician Global AssessmentSubjects achieving GPPPGA pustulation sub score of 0, (%)19 (54)1 (6)Risk difference versus placebo, (95% CI)49 (21, 67)In Study Effisayil-1, subjects in either treatment group who continued to experience flare symptoms at Week were eligible to receive single open-label intravenous dose of 900 mg of SPEVIGO (second dose and first dose for subjects in the SPEVIGO and placebo groups, respectively). At Week 1, 12 (34%) subjects and 15 subjects (83%) in the SPEVIGO and placebo groups, respectively, received open-label SPEVIGO. In subjects who were randomized to SPEVIGO and received an open-label dose of SPEVIGO at Week 1, (42%) subjects had GPPPGA pustulation sub score of at Week (one week after their second dose of SPEVIGO).This study did not include sufficient numbers of subjects to determine if there are differences in response according to biological sex, age, race, baseline GPPPGA pustulation sub score, and baseline GPPPGA total score.. Generalized Pustular Psoriasis Physician Global Assessment (GPPPGA) total score of at least (moderate) [the total GPPPGA score ranges from (clear) to (severe)],. The presence of fresh pustules (new appearance or worsening of pustules),. GPPPGA pustulation sub score of at least (mild), and. At least 5% of body surface area covered with erythema and the presence of pustules.

CLINICAL TRIALS EXPERIENCE SECTION.

6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.SPEVIGO was studied in Study Effisayil-1, randomized, double-blind, placebo-controlled trial comparing single intravenous 900 mg dose of SPEVIGO (n=35) with placebo (n=18) in subjects with generalized pustular psoriasis flare. Subjects in either treatment group who continued to experience flare symptoms at Week were eligible to receive single open-label intravenous dose of 900 mg of SPEVIGO (second dose and first dose for subjects in the SPEVIGO and placebo groups, respectively). At Week 1, 12 (34%) subjects and 15 subjects (83%) in the SPEVIGO and placebo groups, respectively, received open-label SPEVIGO. After Week to Week 12, subjects in either treatment group whose GPP flare reoccurred after achieving clinical response were eligible to receive single open-label rescue intravenous dose of 900 mg of SPEVIGO, with maximum of total doses of SPEVIGO throughout the study. Six subjects received single open-label rescue dose of SPEVIGO. Thirty-six subjects received dose of SPEVIGO, 13 subjects received doses of SPEVIGO, and subjects received doses of SPEVIGO throughout the study [see Clinical Studies (14)].Subjects ranged in age from 21 to 69 years (mean age of 43 years); 45% were White and 55% were Asian; and 68% were female.Table summarizes selected adverse reactions that occurred at rate of at least 1% and at higher rate in the SPEVIGO group than in the placebo group through Week 1.Table 1Selected Adverse Reactions Occurring in >=1% of the SPEVIGO Group and More Frequently than in the Placebo Group through Week (Study Effisayil-1)Adverse ReactionSPEVIGO = 35 (%)Placebo = 18 (%)Asthenia and Fatigue3 (9)0Nausea and Vomiting3 (9)1 (6)Headache3 (9)1 (6)Pruritus and prurigo2 (6)0Infusion site hematoma and bruising2 (6)0Urinary tract infection2 (6)0Bacteremia1 (3)0Bacteriuria1 (3)0Cellulitis1 (3)0Herpes dermatitis and oral herpes1 (3)0Upper respiratory tract infection1 (3)0Dyspnea (3)0Eye edema1 (3)0Urticaria (3)0. Specific Adverse Reactions. InfectionsThe most frequent adverse reactions that occurred in subjects treated with 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 (urinary tract infection) was reported in subject (3%) treated with SPEVIGO and no subjects treated with placebo. Infections observed through Week 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 spesolimab-sbzo. 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.. Safety through Week 12 and 17In Study Effisayil-1, additional adverse reactions that occurred through Week 12 in subjects treated with single dose of randomized SPEVIGO were mild to moderate infections: device-related infection (3%), subcutaneous abscess (3%), furuncle (3%), and influenza (3%).Additional adverse reactions that occurred through Week 17 in subjects treated with single dose of open-label SPEVIGO at Week (second dose and first dose for subjects in the SPEVIGO and placebo groups, respectively) were mild to moderate infections: otitis externa (7%), vulvovaginal candidiasis (4%), vulvovaginal mycotic infection (4%), and latent tuberculosis (4%), diarrhea (11%), and gastritis (4%). No new adverse reactions were identified for up to 16 weeks in subjects treated with single dose of open-label rescue SPEVIGO from Week to Week 12 (range 1-3 total doses).. Clinical Development. Guillain-Barre syndromeAmong approximately 750 subjects exposed to spesolimab-sbzo during clinical development, Guillain-Barre syndrome (GBS) was reported in subjects who received various doses of spesolimab-sbzo via various methods of administration in clinical trials for unapproved indications.. Injection Site ReactionsDuring clinical development, injection site reactions (including injection site erythema, injection site swelling, injection site pain, injection site induration, and injection site warmth) occurred with spesolimab-sbzo.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Administer as 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. (2.1)Must be diluted before use. See full prescribing information for preparation and administration instructions and storage of the diluted solution. (2.2). Administer as 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. (2.1). Must be diluted before use. See full prescribing information for preparation and administration instructions and storage of the diluted solution. (2.2). 2.1 Recommended Dose. Administer SPEVIGO as single 900 mg dose 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.. 2.2 Preparation and Administration Instructions. SPEVIGO must be diluted before use.Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permits. SPEVIGO is colorless to slightly brownish-yellow, clear to slightly opalescent solution. Discard the vial if the solution is cloudy, discolored, or contains large or colored particulates.. PreparationUse aseptic technique to prepare the solution for infusion.Draw and discard 15 mL from 100 mL container of sterile 0.9% Sodium Chloride Injection.Slowly replace with 15 mL of SPEVIGO (complete content from two vials of 450 mg/7.5 mL).Mix gently before use.Use the diluted SPEVIGO solution immediately.. Use aseptic technique to prepare the solution for infusion.. Draw and discard 15 mL from 100 mL container of sterile 0.9% Sodium Chloride Injection.. Slowly replace with 15 mL of SPEVIGO (complete content from two vials of 450 mg/7.5 mL).. Mix gently before use.. Use the diluted SPEVIGO solution immediately.. AdministrationDo not mix SPEVIGO with other medicinal products.Administer SPEVIGO as continuous intravenous infusion through an intravenous line containing sterile, non-pyrogenic, low protein binding in-line filter (pore size of 0.2 micron) over 90 minutes.If the infusion is slowed or temporarily stopped, the total infusion time (including stop time) should not exceed 180 minutes [see Warnings and Precautions (5.3)].A pre-existing intravenous line may be used for administration of SPEVIGO. The line must be flushed with sterile 0.9% Sodium Chloride Injection prior to and at the end of infusion. No other infusion should be administered in parallel via the same intravenous access.No incompatibilities have been observed between SPEVIGO and infusion sets composed of polyvinylchloride (PVC), polyethylene (PE), polypropylene (PP), polybutadiene and polyurethane (PUR), and in-line filter membranes composed of polyethersulfone (PES, neutral and positively charged) and positively charged polyamide (PA).. Do not mix SPEVIGO with other medicinal products.. Administer SPEVIGO as continuous intravenous infusion through an intravenous line containing sterile, non-pyrogenic, low protein binding in-line filter (pore size of 0.2 micron) over 90 minutes.. If the infusion is slowed or temporarily stopped, the total infusion time (including stop time) should not exceed 180 minutes [see Warnings and Precautions (5.3)].. pre-existing intravenous line may be used for administration of SPEVIGO. The line must be flushed with sterile 0.9% Sodium Chloride Injection prior to and at the end of infusion. No other infusion should be administered in parallel via the same intravenous access.. No incompatibilities have been observed between SPEVIGO and infusion sets composed of polyvinylchloride (PVC), polyethylene (PE), polypropylene (PP), polybutadiene and polyurethane (PUR), and in-line filter membranes composed of polyethersulfone (PES, neutral and positively charged) and positively charged polyamide (PA).. Storage of Diluted SolutionIf not administered immediately, refrigerate the diluted solution at 2C to 8C (36F to 46F) for no more than hours. Protect from light.. 2.3 Testing and Procedures Prior to Treatment Initiation. Evaluate patients for 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)].

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. population pharmacokinetic model was developed based on data collected from healthy subjects, patients with GPP, and patients with other diseases. After single intravenous dose of 900 mg of SPEVIGO, the population PK model-estimated AUC0- (95% CI) and Cmax (95% CI) in typical anti-drug antibody (ADA)-negative patient with GPP were 4750 (4510, 4970) mcgday/mL and 238 (218, 256) mcg/mL, respectively.Spesolimab-sbzo AUC increased dose-proportionally from 0.3 to 20 mg/kg, and CL and terminal half-life were independent of dose.. DistributionBased on the population pharmacokinetic analysis, the typical total volume of distribution at steady state was 6.4 L.. Elimination. MetabolismThe metabolic pathway of spesolimab-sbzo has not been characterized. As humanized IgG1 monoclonal antibody, spesolimab-sbzo is expected to be degraded into small peptides and amino acids via catabolic pathways in manner similar to endogenous IgG.. ExcretionIn the linear dose range (0.3 to 20 mg/kg), based on the population PK model, spesolimab-sbzo clearance (95% CI) in typical GPP patient without ADA, weighing 70 kg was 0.184 (0.175, 0.194) L/day. The terminal half-life was 25.5 (24.4, 26.3) days.. Specific Populations. Age, Gender, and RaceBased on population pharmacokinetic analyses, age, gender, and race did not have an effect on the pharmacokinetics of spesolimab-sbzo.. Hepatic and Renal ImpairmentAs monoclonal antibody, spesolimab-sbzo is not expected to undergo hepatic or renal elimination. No formal study of the effect of hepatic or renal impairment on the pharmacokinetics of spesolimab-sbzo was conducted.. Body WeightSpesolimab-sbzo concentrations were lower in subjects with higher body weight. The clinical impact of body weight on spesolimab-sbzo plasma concentrations is unknown.. Drug Interaction StudiesNo formal drug interactions studies have been conducted with spesolimab-sbzo.

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryThe limited data on the use of SPEVIGO in pregnant women are insufficient to inform drug-associated risk of adverse pregnancy-related outcomes. Human IgG is known to cross the placental barrier; therefore, SPEVIGO may be transmitted from the mother to the developing fetus. In an animal reproduction study, intravenous administration of surrogate antibody against IL36R in mice during the period of organogenesis did not elicit any reproductive toxicity (see Data).All pregnancies have background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.. Data. Animal DataEmbryo-fetal development and pre- and postnatal development toxicity studies were performed in mice using surrogate mouse specific IL36R antagonist monoclonal antibody. In the embryo-fetal development study, the surrogate was administered intravenously at doses up to 50 mg/kg to pregnant female mice twice weekly during the period of organogenesis. The surrogate was not associated with embryo-fetal lethality or fetal malformations. In the pre- and postnatal development toxicity study, the surrogate was administered intravenously at doses up to 50 mg/kg to pregnant female mice twice weekly from gestation day through lactation day 18. There were no maternal effects observed. There were no treatment-related effects observed on postnatal developmental, neurobehavioral, or reproductive performance of offspring.

SPL MEDGUIDE SECTION.

MEDICATION GUIDE SPEVIGO(R) (spea VEE go) (spesolimab-sbzo) injection, for intravenous useThis Medication Guide has been approved by the U.S. Food and Drug Administration.Issued: September 2022What is the most important information should know about SPEVIGOSPEVIGO may cause serious side effects, including:Infections. SPEVIGO may lower the ability of your immune system to fight infections and may increase your risk of infections. Your healthcare provider should check you for infections and tuberculosis (TB) before starting treatment with SPEVIGO and may treat you for TB before you begin treatment with SPEVIGO if you have history of TB or have active TB. Your healthcare provider should watch you closely for signs and symptoms of TB after treatment with SPEVIGO. Tell your healthcare provider right away if you have an infection or have symptoms of an infection, including:fevers, chills, or sweatsmuscle achescoughshortness of breathblood in your phlegm (mucus)burning when you urinateurinating more often than normalAllergic reactions and infusion-related reactions. Serious allergic reactions may happen during or after your infusion of SPEVIGO. If you have serious allergic reaction, your healthcare provider will stop treatment with SPEVIGO. If you have an infusion-related reaction, your healthcare provider will stop your SPEVIGO infusion and treat your symptoms and may restart SPEVIGO at slower infusion rate. Tell your healthcare provider or get emergency medical help right away if you get any of the following symptoms during or after your infusion of SPEVIGO:feeling faint, dizzy, or lightheadedswelling of your face, eyelids, lips, mouth, tongue, or throattrouble breathing or throat tightnessfevermouth soreschest tightnesshives or skin rash that is different than the rash from generalized pustular psoriasis (GPP)itchingswollen lymph nodesSee What are the possible side effects of SPEVIGO for more information about side effects.What is SPEVIGOSPEVIGO is prescription medicine used to treat generalized pustular psoriasis (GPP) flares in adults.It is not known if SPEVIGO is safe and effective in children.Do not receive SPEVIGO if you have had severe or life-threatening allergic reaction to spesolimab-sbzo or any of the ingredients in SPEVIGO. See the end of this Medication Guide for complete list of ingredients in SPEVIGO.Before you receive SPEVIGO, tell your healthcare provider about all of your medical conditions, including if you:have an infection that does not go away or that keeps coming back. See What is the most important information should know about SPEVIGO have TB or have been in close contact with someone with TB.have recently received or are scheduled to receive an immunization (vaccine). You should not receive live vaccines after treatment with SPEVIGO.are pregnant or plan to become pregnant. It is not known if SPEVIGO can harm your 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 baby during treatment with SPEVIGO.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.How will receive SPEVIGOYour healthcare provider will give you SPEVIGO through needle placed in your vein (intravenous infusion) over 90 minutes.SPEVIGO is usually given one time. If GPP flare symptoms continue, your healthcare provider will decide if you should receive an additional treatment with SPEVIGO after week.What are the possible side effects of SPEVIGOSPEVIGO may cause serious side effects. See What is the most important information should know about SPEVIGOThe most common side effects of SPEVIGO include:feeling tired or weaknausea and vomitingheadacheitching or itchy bumpsa collection of blood under the skin at the infusion site or bruisingurinary tract infectionThese are not all of the possible side effects of SPEVIGO.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.General information about the safe and effective use of SPEVIGO.Medicines are sometimes prescribed for purposes other than those listed in Medication Guide. You can ask your pharmacist or healthcare provider for information about SPEVIGO that is written for health professionals.What are the ingredients in SPEVIGOActive ingredient: spesolimab-sbzoInactive ingredients: arginine hydrochloride, glacial acetic acid, polysorbate 20, sodium acetate, sucrose, and Water for Injection, USPManufactured by: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877 USAUS License Number 2006Licensed from: Boehringer Ingelheim International GmbH, Ingelheim, GermanySPEVIGO is registered trademark of and used under license from Boehringer Ingelheim International GmbH.Copyright (C) 2022 Boehringer Ingelheim International GmbH ALL RIGHTS RESERVEDCOL9614AH012022For 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.. Infections. SPEVIGO may lower the ability of your immune system to fight infections and may increase your risk of infections. Your healthcare provider should check you for infections and tuberculosis (TB) before starting treatment with SPEVIGO and may treat you for TB before you begin treatment with SPEVIGO if you have history of TB or have active TB. Your healthcare provider should watch you closely for signs and symptoms of TB after treatment with SPEVIGO. Tell your healthcare provider right away if you have an infection or have symptoms of an infection, 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 infusion of SPEVIGO. If you have serious allergic reaction, your healthcare provider will stop treatment with SPEVIGO. If you have an infusion-related reaction, your healthcare provider will stop your SPEVIGO infusion and treat your symptoms and may restart SPEVIGO at slower infusion rate. Tell your healthcare provider or get emergency medical help right away if you get any of the following symptoms during or after your infusion of SPEVIGO:. 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. have an infection that does not go away or that keeps coming back. See What is the most important information should know about SPEVIGO have TB or have been in close contact with someone with TB.. have recently received or are scheduled to receive an immunization (vaccine). You should not receive live vaccines after treatment with SPEVIGO.. are pregnant or plan to become pregnant. It is not known if SPEVIGO can harm your 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 baby during treatment with SPEVIGO.. Your healthcare provider will give you SPEVIGO through needle placed in your vein (intravenous infusion) over 90 minutes.. SPEVIGO is usually given one time. If GPP flare symptoms continue, your healthcare provider will decide if you should receive an additional treatment with SPEVIGO after week.. feeling tired or weak. nausea and vomiting. headache. itching or itchy bumps. collection of blood under the skin at the infusion site or bruising. urinary tract infection. Image.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk SummaryThe limited data on the use of SPEVIGO in pregnant women are insufficient to inform drug-associated risk of adverse pregnancy-related outcomes. Human IgG is known to cross the placental barrier; therefore, SPEVIGO may be transmitted from the mother to the developing fetus. In an animal reproduction study, intravenous administration of surrogate antibody against IL36R in mice during the period of organogenesis did not elicit any reproductive toxicity (see Data).All pregnancies have background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.. Data. Animal DataEmbryo-fetal development and pre- and postnatal development toxicity studies were performed in mice using surrogate mouse specific IL36R antagonist monoclonal antibody. In the embryo-fetal development study, the surrogate was administered intravenously at doses up to 50 mg/kg to pregnant female mice twice weekly during the period of organogenesis. The surrogate was not associated with embryo-fetal lethality or fetal malformations. In the pre- and postnatal development toxicity study, the surrogate was administered intravenously at doses up to 50 mg/kg to pregnant female mice twice weekly from gestation day through lactation day 18. There were no maternal effects observed. There were no treatment-related effects observed on postnatal developmental, neurobehavioral, or reproductive performance of offspring.. 8.2 Lactation. Risk SummaryThere are no data on the presence of spesolimab-sbzo in human milk, the effects on the breastfed infant, or the effects on milk production. Spesolimab-sbzo is monoclonal antibody and is expected to be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for SPEVIGO and any potential adverse effects on the breastfed infant from SPEVIGO or from the underlying maternal condition.. 8.4 Pediatric Use. The safety and effectiveness of SPEVIGO in pediatric patients have not been established.. 8.5 Geriatric Use. In Study Effisayil-1, (6%) of SPEVIGO-treated subjects were 65 to 74 years of age and no subjects were 75 years of age or older. Clinical studies of SPEVIGO did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger adult subjects.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Infections: SPEVIGO may increase the risk of infections. Do not initiate SPEVIGO during any clinically important active infection. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur after treatment with SPEVIGO. (5.1)Tuberculosis (TB): Evaluate patients for TB prior to initiating treatment with SPEVIGO. (5.2)Hypersensitivity and Infusion-Related Reactions: Hypersensitivity including drug reaction with eosinophilia and systemic symptoms (DRESS) and infusion-related reactions may occur. If serious hypersensitivity reaction occurs, discontinue SPEVIGO immediately and initiate appropriate treatment. (5.3)Vaccinations: Do not administer live vaccines concurrently with SPEVIGO. (5.4). Infections: SPEVIGO may increase the risk of infections. Do not initiate SPEVIGO during any clinically important active infection. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur after treatment with SPEVIGO. (5.1). Tuberculosis (TB): Evaluate patients for TB prior to initiating treatment with SPEVIGO. (5.2). Hypersensitivity and Infusion-Related Reactions: Hypersensitivity including drug reaction with eosinophilia and systemic symptoms (DRESS) and infusion-related reactions may occur. If serious hypersensitivity reaction occurs, discontinue SPEVIGO immediately and initiate appropriate treatment. (5.3). Vaccinations: Do not administer live vaccines concurrently with SPEVIGO. (5.4). 5.1 Infections. 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 chronic infection or history of recurrent infection, consider the potential risks and expected clinical benefits of treatment prior to prescribing SPEVIGO. Treatment with SPEVIGO is not recommended for use 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 after treatment with SPEVIGO.. 5.2 Risk of Tuberculosis. Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with SPEVIGO. Do not administer SPEVIGO to patients with active TB infection.Consider initiating anti-TB therapy prior to initiating SPEVIGO in patients with latent TB or 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.. 5.3 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 [see Adverse Reactions (6.1)].If patient develops signs of anaphylaxis or other serious hypersensitivity, discontinue SPEVIGO immediately and initiate appropriate treatment [see Contraindications (4)].If patient develops mild or moderate 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 slower infusion rate with gradual increase to complete the infusion.. 5.4 Vaccinations. Avoid use of live vaccines in patients treated with SPEVIGO. No specific studies have been conducted in SPEVIGO-treated patients who have recently received live viral or live bacterial vaccines.