BRIEF SUMMARY-

SPESOLIMAB-(Sep 2022)

Indn- To Treat Generalized postular psoriasis flares   

Comp- Injection: 450 mg/7.5 mL (60 mg/mL) solution in a single-dose vial-           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.

• Must be diluted before use. .

ADR- Most common adverse reactions  are asthenia and fatigue, nausea and vomiting, headache, pruritus and prurigo, infusion site hematoma and bruising, and urinary tract infection

 CONTRAINDICATIONS-

 Severe or life-threatening hypersensitivity to spesolimab-sbzo or to any of the excipients

WARNINGS-

 Infections: may increase the risk of infections. Do not initiate  during any clinically important active infection. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur

 Tuberculosis (TB): Evaluate patients for TB prior to initiating treatment with SPEVIGO.

 Hypersensitivity and Infusion-Related Reactions: Hypersensitivity including drug reaction with eosinophilia and systemic symptoms (DRESS) and infusion-related reactions may occur. If a serious hypersensitivity reaction occurs, discontinue immediately and initiate appropriate treatment.

 Vaccinations: Do not administer live vaccines concurrently

Pat inform-

 Infections Inform patients that SPEVIGO may lower the ability of their immune system to fight infections.

Instruct patients of the importance of communicating any history of infections to the healthcare provider and contacting  their healthcare provider if they develop any signs or symptoms of clinically important infection 

Hypersensitivity and Infusion-Related Reactions-                                                   Inform patients that hypersensitivity and infusion-related reactions may occur

Advise patients to seek immediate medical attention if they experience any symptoms of a serious hypersensitivity reaction

 Vaccinations-                                                                                                          Advise patients to avoid receiving live vaccines after treatment 

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U.S.  APPROVED DRUGS SURING 2022                                        

Serial No 18

Name-                        SPESOLIMAB

Active Ingredient -   Spesolimab-sbzo 

Pharmacological Classification- To Treat Generalized postular psoriasis flares      

                                                                                                                                             Date of Approval-         9/1/2022   

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use                          SPEVIGO safely and effectively.                                                                                    See full prescribing information for SPEVIGO. SPEVIGO® (spesolimab-sbzo) injection, for intravenous use

Initial U.S. Approval: 2022

INDICATIONS AND USAGE-

 SPEVIGO is an interleukin-36 receptor antagonist indicated for the treatment of generalized pustular psoriasis flares in adults.

ADVERSE REACTIONS-

 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. 

CONTRAINDICATIONS-

 Severe or life-threatening hypersensitivity to spesolimab-sbzo or to any of the excipients in SPEVIGO (

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.

 • Tuberculosis (TB): Evaluate patients for TB prior to initiating treatment with SPEVIGO.

 • Hypersensitivity and Infusion-Related Reactions: Hypersensitivity including drug reaction with eosinophilia and systemic symptoms (DRESS) and infusion-related reactions may occur. If a serious hypersensitivity reaction occurs, discontinue SPEVIGO immediately and initiate appropriate treatment.

 • Vaccinations: Do not administer live vaccines concurrently with SPEVIGO.

DOSAGE AND ADMINISTRATION-

 • 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.

 • Must be diluted before use. See full prescribing information for preparation and administration instructions and storage of the diluted solution.

DOSAGE FORMS AND STRENGTHS-

 Injection: 450 mg/7.5 mL (60 mg/mL) solution in a single-dose vial

PATIENT COUNSELING INFORMATION-

Advise the patient to read the FDA-approved patient labeling (Medication Guide). Infections Inform patients that SPEVIGO may lower the ability of their immune system to fight infections.

Instruct patients of the importance of communicating any history of infections to the healthcare provider and contacting  their healthcare provider if they develop any signs or symptoms of clinically important infection 

Hypersensitivity and Infusion-Related Reactions-                                                    Inform patients that hypersensitivity and infusion-related reactions may occur with SPEVIGO.

Advise patients to seek immediate medical attention if they experience any symptoms of a serious hypersensitivity reaction

 Vaccinations-                                                                                                          Advise patients to avoid receiving live vaccines after treatment with SPEVIGO

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.

CLINICAL PHARMACOLOGY

1 Mechanism of Action-                                                                                   Spesolimab-sbzo is a humanized monoclonal immunoglobulin G1 antibody that inhibits interleukin-36 (IL-36) signaling by specifically binding to the IL36R.

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

3. Pharmacokinetics-                                                                                                       A population pharmacokinetic model was developed based on data collected from healthy subjects, patients with GPP, and patients with other diseases.

Spesolimab-sbzo AUC increased dose-proportionally from 0.3 to 20 mg/kg, and CL and terminal half-life were independent of dose.

Distribution-                                                                                                               Based on the population pharmacokinetic analysis, the typical total volume of distribution at steady state was 6.4 L

 Elimination Metabolism-                                                                                             The metabolic pathway of spesolimab-sbzo has not been characterized.

Excretion-                                                                                                                         In the linear dose range (0.3 to 20 mg/kg), based on the population PK model, spesolimab-sbzo clearance (95% CI) in a typical GPP patient without ADA, weighing 70 kg was 0.184 (0.175, 0.194) L/day.

The terminal halflife was 25.5 (24.4, 26.3) days.

Specific Populations Age, Gender, and Race -                                                       Based on population pharmacokinetic analyses, age, gender, and race did not have an effect on the pharmacokinetics of spesolimab-sbzo.

Hepatic and Renal Impairment-                                                                                    As a 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 Weight Spesolimab-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 Studies-                                                                                              No formal drug interactions studies have been conducted with spesolimab-sbzo.

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

 Anti-Drug Antibody Effects on Pharmacokinetics-                                                       In 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 a subsequent, new flare in an open-label extension trial.

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USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary-                                                                                      The limited data on the use of SPEVIGO in pregnant women are insufficient to inform a drug-associated risk of adverse pregnancy-related outcomes.

All pregnancies have a 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

2. Lactation Risk Summary                                                                                       There 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 a monoclonal antibody and is expected to be present in human milk.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for SPEVIGO and any potential adverse effects on the breastfed infant from SPEVIGO or from the underlying maternal condition.

3. Pediatric Use-                                                                                                            The safety and effectiveness of SPEVIGO in pediatric patients have not been established.

4. Geriatric Use-                                                                                                               In Study Effisayil-1, 2 (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.