BRIEF SUMMARY

TEZEPELIMAB-(Dec 2021Indn

Indn-    To treat severe asthma

Comp-   injection: 210 mg/1.91 mL (110 mg/mL) solution in a single-dose glass vial.        210 mg/1.91 mL (110 mg/mL) solution in a single-dose pre-filled syringe.

ADR-   -

 Most common adverse reactions (incidence = 3%) are pharyngitis, arthralgia, and back pain.

CI-    Known hypersensitivity to tezepelumab-ekko or excipients.

Pat Inform-

Hypersensitivity Reactions-

Inform patients that hypersensitivity reactions (e.g., rash and allergic conjunctivitis) can occur following administration..                                                                                 

 These reactions can occur within hours of administration, but in some instances have a delayed onset (i.e., days).                                                                                           

Instruct patients to contact their healthcare provider if they experience symptoms of an allergic reaction .

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U.S. FDA APPROVED DRUGS SURING 2021                                          

Serial No 48

Name of the Drug-    TEZPIRE

Active Ingredient -   Tezepelumab

Pharmacological Classification-   To treat severe asthma                                                               

                                                                                                                                               Date of Approval-          12/17/2021

HIGHLIGHTS OF PRESCRIBING INFORMATION-

These highlights do not include all the information needed to use                              TEZSPIRE safely and effectively.                                                                                    See full prescribing information for TEZSPIRE. TEZSPIRE™ (tezepelumab-ekko) injection, for subcutaneous use

Initial U.S. Approval: 2021

 INDICATIONS AND USAGE-

 TEZSPIRE is a thymic stromal lymphopoietin (TSLP) blocker, human monoclonal antibody (IgG2?), indicated for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma.

 Limitations of Use: ? Not for relief of acute bronchospasm or status asthmaticus. 

DOSAGE AND ADMINISTRATION-

 Administer by subcutaneous injection.   Recommended dosage is 210 mg administered once every 4 weeks.

 DOSAGE FORMS AND STRENGTHS-

 Injection: ? 210 mg/1.91 mL (110 mg/mL) solution in a single-dose glass vial.                   210 mg/1.91 mL (110 mg/mL) solution in a single-dose pre-filled syringe.-

 CONTRAINDICATIONS

 Known hypersensitivity to tezepelumab-ekko or excipients.

 ADVERSE REACTIONS-

 Most common adverse reactions (incidence = 3%) are pharyngitis, arthralgia, and back pain.

------------------ WARNINGS AND PRECAUTIONS ---------------------- ? Hypersensitivity Reactions: Hypersensitivity reactions (e.g., rash, allergic conjunctivitis) can occur after administration of TEZSPIRE. Initiate appropriate treatment as clinically indicated in the event of a hypersensitivity reaction. (5.1) ? Risk Associated with Abrupt Reduction in Corticosteroid Dosage: Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with TEZSPIRE. Decrease corticosteroids gradually, if appropriate. (5.3) ? Parasitic (Helminth) Infection: Treat patients with pre-existing helminth infections before therapy with TEZSPIRE. If patients become infected while receiving TEZSPIRE and do not respond to antihelminth treatment, discontinue TEZSPIRE until the parasitic infection resolves. (5.4) ? Vaccination: Avoid use of live attenuated vaccines.

 ADVERSE REACTIONS-

 Most common adverse reactions (incidence = 3%) are pharyngitis, arthralgia, and back pain.

 DOSAGE AND ADMINISTRATION-

 Administer by subcutaneous injection. (2) ? Recommended dosage is 210 mg administered once every 4 weeks.

 DOSAGE FORMS AND STRENGTHS-

 Injection: 210 mg/1.91 mL (110 mg/mL) solution in a single-dose glass vial.

 210 mg/1.91 mL (110 mg/mL) solution in a single-dose pre-filled syringe.

 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information).

Hypersensitivity Reactions-

Inform patients that hypersensitivity reactions (e.g., rash and allergic conjunctivitis) can occur following administration of TEZSPIRE [see Contraindications (4) and Adverse Reactions (6)].

These reactions can occur within hours of administration, but in some instances have a delayed onset (i.e., days).

Instruct patients to contact their healthcare provider if they experience symptoms of an allergic reaction .

Not for Acute Symptoms or Deteriorating Disease-                                                    Inform patients that TEZSPIRE does not treat acute asthma symptoms or acute exacerbations. Inform patients to seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with TEZSPIRE].

Risk Associated with Abrupt Reduction of Corticosteroid Dosage-                     Inform patients to not discontinue systemic or inhaled corticosteroids except under the direct supervision of a healthcare provider.

Inform patients that reduction in corticosteroid dose may be associated with systemic withdrawal symptoms  and/or unmask conditions previously suppressed by systemic corticosteroid therapy 

Administration of Vaccines- Instruct patients to inform the healthcare provider that they are taking TEZSPIRE prior to a potential vaccination .

Manufactured by: AstraZeneca AB, Sodertalje, Sweden SE-15185 US License No. 2059 At: Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799 Marketed by: Amgen Inc. and AstraZeneca AB ©AstraZeneca and Amgen 2021 TEZSPIRE is a trademark of Amgen Inc.

CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Tezepelumab-ekko is a thymic stromal lymphopoietin (TSLP) blocker, human monoclonal antibody IgG2? that binds to human TSLP with a dissociation constant of 15.8 pM and blocks its interaction with the heterodimeric TSLP receptor. TSLP is a cytokine mainly derived from epithelial cells and occupies an upstream position in the asthma inflammatory cascade. Airway inflammation is an important component in the pathogenesis of asthma. Multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes, ILC2 cells) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) are involved in airway inflammation. Blocking TSLP with tezepelumab-ekko reduces biomarkers and cytokines associated with inflammation including blood eosinophils, airway submucosal eosinophils, IgE, FeNO, IL-5, and IL-13; however, the mechanism of tezepelumab-ekko action in asthma has not been definitively established. 12.2 Pharmacodynamics In NAVIGATOR, administration of TEZSPIRE 210 mg subcutaneously every 4 weeks (n=528) reduced blood eosinophils counts, FeNO, IL-5 concentration and IL-13 concentration from baseline compared with placebo (n=531) with an onset of effect 2 weeks after initiation of treatment and sustained reduction on treatment to 52 weeks. TEZSPIRE caused a slow but progressive reduction in serum total IgE concentration throughout 52 weeks of treatment. Similar effects were seen in PATHWAY. 12.3 Pharmacokinetics The pharmacokinetics of tezepelumab-ekko were dose-proportional following administration of a single subcutaneous dose over a dose range from 2.1 mg to 420 mg (0.01 to 2 times the recommended dose). With an every 4 weeks dosing regimen, tezepelumab-ekko achieves steady-state after 12 weeks and the accumulation ratio for Ctrough is 1.86-fold. Absorption Following subcutaneous administration, the maximum serum concentration was reached in approximately 3 to 10 days. Based on population pharmacokinetic analysis, the estimated absolute bioavailability was approximately 77%. There was no clinically relevant difference in bioavailability when administered to different injection sites (abdomen, thigh, or upper arm). Distribution Based on population pharmacokinetic analysis, central and peripheral volume of distribution of tezepelumab-ekko were 3.9 L and 2.2 L, respectively, for a 70 kg individual. Elimination As a human monoclonal antibody, tezepelumab-ekko is eliminated by intracellular catabolism and there is no evidence of target-mediated clearance within the studied dose range. Based on population pharmacokinetic analysis, the estimated clearance for tezepelumab-ekko was 0.17 L/d for a 70 kg individual. The elimination half-life was approximately 26 days. Metabolism Tezepelumab-ekko is a human monoclonal antibody (IgG2?) that is degraded by proteolytic enzymes widely distributed in the body and not metabolized by hepatic enzymes. Reference ID: 4907025 Specific Populations Age, Sex, Race Based on population pharmacokinetic analysis, age (12 to 80 years), sex and race (White, Black, Asian, Other) had no clinically meaningful effects on the pharmacokinetics of tezepelumab-ekko. Body Weight Based on population pharmacokinetic analysis, higher body weight was associated with lower exposure. However, the effect of body weight on exposure had no meaningful impact on efficacy or safety and does not require dose adjustment. Patients with Renal impairment No formal clinical studies have been conducted to investigate the effect of renal impairment on tezepelumab-ekko. The population pharmacokinetic analysis included 320 (23%) subjects with mild renal impairment and 38 (3%) subjects with moderate renal impairment. Tezepelumab-ekko clearance was similar in patients with mild renal impairment (estimated creatinine clearance 60 to 89 mL/min), moderate renal impairment (estimated creatinine clearance 30 to 59 mL/min) and those with normal renal function (estimated creatinine clearance = 90 mL/min). Tezepelumab-ekko has not been studied in patients with severe renal impairment (estimated creatinine clearance < 30 mL/min). Patients with Hepatic impairment No formal clinical studies have been conducted to investigate the effect of hepatic impairment on tezepelumab-ekko. Since tezepelumab-ekko is degraded by proteolytic enzymes widely distributed in the body and not metabolized by hepatic-specific enzymes, change in hepatic function is not expected to influence tezepelumab-ekko clearance. Drug Interaction Studies No formal drug interaction studies have been conducted with tezepelumab-ekko. Based on the population pharmacokinetic analysis, commonly co-administered asthma medications (leukotriene receptor antagonist, theophylline/aminophylline, oral and inhaled corticosteroid) had no clinically meaningful effect on tezepelumab-ekko clearance.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Animal studies have not been conducted to evaluate the carcinogenic potential of tezepelumab-ekko. The malignancy risk in humans from an antibody that blocks TSLP ligand, such as tezepelumab-ekko, is currently unknown. Male and female fertility was unaffected based upon no observed adverse histopathological findings in the reproductive organs and no changes in menstrual cycle or semen analysis in sexually mature cynomolgus monkeys that received tezepelumab-ekko for 26 weeks at subcutaneous doses up to 300 mg/kg/week (approximately 134 times the MRHD on an AUC basis)

7 DRUG INTERACTIONS No formal drug interaction studies have been performed with TEZSPIRE. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no available data on TEZSPIRE use in pregnant women to evaluate for any drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. In an enhanced pre- and post-natal development (ePPND) study conducted in cynomolgus monkeys, placental transport of tezepelumab-ekko was observed but there was no evidence of fetal harm following intravenous administration of tezepelumab-ekko throughout pregnancy at doses that produced maternal exposures up to 168 times the exposure at the maximum recommended human dose (MRHD) of 210 mg administered subcutaneously [see Data]. The estimated background risk of major birth defects and miscarriages for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk: In women with poorly or moderately controlled asthma, evidence demonstrates that there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. The level of asthma control should be closely monitored in pregnant women and treatment adjusted as necessary to maintain optimal control. Data Animal Data In the ePPND study, pregnant cynomolgus monkeys received tezepelumab-ekko from GD20 to GD22 (dependent on pregnancy determination), at the beginning of organogenesis, and once every 7 days until the end of gestation at doses that produced exposures up to 168 times that achieved with the MRHD (on an AUC basis with maternal intravenous doses up to 300 mg/kg/week). There were no tezepelumab-ekko related adverse effects on maternal health, pregnancy outcome, Reference ID: 4907025 embryo-fetal development, or neonatal growth and development up to 6.5 months of age. Tezepelumab-ekko crossed the placenta in cynomolgus monkeys and tezepelumab-ekko serum concentrations were 0.5- to 6.7-fold higher in infants relative to maternal animals. 8.2 Lactation Risk Summary There is no information regarding the presence of tezepelumab-ekko in human milk, its effects on the breastfed infant, or its effects on milk production. However, tezepelumab-ekko is a human monoclonal antibody immunoglobulin G2? (IgG2?), and immunoglobulin G (IgG) is present in human milk in small amounts. Tezepelumab-ekko was present in the milk of cynomolgus monkeys postpartum following dosing during pregnancy [see Data]. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for TEZSPIRE and any potential adverse effects on the breastfed infant from TEZSPIRE or from the underlying maternal condition. Data Animal Data In a prenatal and postnatal development study in cynomolgus monkeys, tezepelumab-ekko concentrations in milk were up to 0.5% of the maternal serum concentrations after intravenous administration of tezepelumab-ekko up to 300 mg/kg/week (168 times the exposures based on AUC achieved at MRHD). The concentration of tezepelumab-ekko in animal milk does not necessarily predict the concentration of drug in human milk. 8.4 Pediatric Use The safety and effectiveness of TEZSPIRE for the add-on maintenance treatment of severe asthma have been established in pediatric patients aged 12 years and older [see Adverse Reactions (6.1) and Clinical Studies (14)]. Use of TEZSPIRE for this indication is supported by evidence from a total of 82 pediatric patients aged 12 to 17 years enrolled in NAVIGATOR and received treatment with TEZSPIRE 210 mg subcutaneously every 4 weeks (n=41) or placebo (n=41). Compared with placebo, improvements in annualized asthma exacerbation (rate ratio 0.70; 95% CI 0.34, 1.46) and FEV1 (LS mean change versus placebo 0.17 L; 95% CI -0.01, 0.35) were observed in pediatric patients treated with TEZSPIRE. The safety profile and pharmacodynamic responses in pediatric patients were generally similar to the overall study population. The safety and effectiveness in patients younger than 12 years of age have not been established. 8.5 Geriatric Use Of the 665 patients with asthma treated with TEZSPIRE in clinical trials (PATHWAY and NAVIGATOR) for severe asthma, 119 patients (18%) were 65 years or older. No overall differences in safety or effectiveness of TEZSPIRE have been observed between patients 65 years of age and older and younger patients [see Adverse Reactions (6.1) and Clinical Studies (14)].

11 DESCRIPTION Tezepelumab-ekko, a thymic stromal lymphopoietin (TSLP) blocker, is a human monoclonal antibody immunoglobulin G2? (IgG2?) produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology. Tezepelumab-ekko has a molecular weight of approximately 147 kDa. TEZSPIRE (tezepelumab-ekko) injection is a st