DRUG INTERACTIONS-(details)

TECVAYLI causes release of cytokines  that may suppress activity of cytochrome P450 (CYP) enzymes, resulting in increased exposure of CYP substrates.

The highest risk of drug-drug interaction is expected to occur from initiation of TECVAYLI stepup dosing schedule up to 7 days after the first treatment dose and during and after CRS 

Monitor for toxicity or concentrations of drugs that are CYP substrates where minimal concentration changes may lead to serious adverse reactions. Adjust the dose of the concomitant CYP substrate drug as needed.

BRIEF SUMMARY

TECLISTAB-cqyr-(Oct 2022)

Indn-To treat relapsed or refractory multipe  myloma  among adults who have received at east four specific lines of therapy      

Comp-  For subcutaneous injection only.                                                                  Dosing Schedule Day Dose Step-up Dosing Schedule                                                        Day 1 Step-up dose 1 0.06 mg/kg                                                                                        Day 4 Step-up dose 2 0.3 mg/kg                                                                                          Day 7 First treatment dose 1.5 mg/kg                                                                                  Weekly Dosing Schedule One week after first treatment dose and weeklyt treatment doses 1.5 mg/kg once weekly.                                                                             Subsequent treatment doses 1.5 mg/kg once weekly

ADR-  The most common adverse reactions  are pyrexia, cytokine release syndrthereafteome, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea.treament doses 1.5 mg/kg once weekly

CI- None.

WARNINGS -

  Hepatotoxicity: Can cause hepatotoxicity, including fatalities. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated.

  Infections: Can cause severe, life-threatening, or fatal infections. Monitor patients for signs and symptoms of infection and treat appropriately. Withhold in patients with active infection during the step-up dosing schedule.

Pat Inform-

Cytokine Release Syndrome (CRS)-                                                                         Discuss the signs and symptoms associated with CRS, including fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes.

Advise patients to immediately contact their healthcare provider if they experience any signs or symptoms of CRS.

Advise patients that they will be hospitalized for 48 hours after administration of all doses within the  step-up dosing schedule

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U.S.  APPROVED DRUGS SURING 2022                                        

Serial No 28

Name-        TECVAYLI

Active  Ingredient -  Teclistab-cqyr

Pharmacological clssificiation-        To treat relapsed or refractory multipe                                                                             myloma  among adults who have received at                                                                east four specific lines of therapy                                                                                                                                                                    Date of Approved-         10/25/2022                           

  HIGHLIGHTS OF PRESCRIBING INFORMATION

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

Initial U.S. Approval: 2022

WARNING:                                                                                                               CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME-                See full prescribing information for complete boxed warning.

Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TECVAYLI. Initiate treatment with TECVAYLI step-up dosing schedule to reduce risk of CRS.

Withhold TECVAYLI until CRS resolves or permanently discontinue based on severity.

Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and serious and life-threatening reactions, can occur in patients receiving TECVAYLI.

Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold TECVAYLI until neurologic toxicity resolves or permanently discontinue based on severity.

TECVAYLI is available only through a restricted program called the TECVAYLI Risk Evaluation and Mitigation Strategy (REMS).

INDICATIONS AND USAGE-

 TECVAYLI is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.

This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

ADVERSE REACTIONS-

 The most common adverse reactions (=20%) are pyrexia, cytokine release syndrome, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea.

The most common Grade 3 to 4 laboratory abnormalities (=20%) are decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets.

CONTRAINDICATIONS-

 None.

WARNINGS AND PRECAUTIONS-

 • Hepatotoxicity: Can cause hepatotoxicity, including fatalities. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated.

 • Infections: Can cause severe, life-threatening, or fatal infections. Monitor patients for signs and symptoms of infection and treat appropriately. Withhold in patients with active infection during the step-up dosing schedule.

 • Neutropenia: Monitor complete blood cell counts at baseline and periodically during treatment.

• Hypersensitivity and Other Administration Reactions: Systemic administration-related reactions and local injection site reactions can occur. Withhold or consider permanent discontinuation based on severity.

 • Embryo-Fetal Toxicity: May cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception.

DOSAGE AND ADMINISTRATION-

 TECVAYLI Recommended Dosing Schedule

 Dosing Schedule Day Dose Step-up Dosing Schedule                                                        Day 1 Step-up dose 1 0.06 mg/kg                                                                                        Day 4 Step-up dose 2 0.3 mg/kg                                                                                          Day 7 First treatment dose 1.5 mg/kg                                                                                  Weekly Dosing Schedule One week after first treatment dose and weekly thereafter Subsequent treatment doses 1.5 mg/kg once weekly

• For subcutaneous injection only. 

Patients should be hospitalized for 48 hours after administration of all doses within the TECVAYLI step-up dosing schedule.

• Administer pretreatment medications as recommended.

 • See Full Prescribing Information for instructions on preparation and administration.

DOSAGE FORMS AND STRENGTHS-

 Injection • 30 mg/3 mL (10 mg/mL) in a single-dose vial                                                     • 153 mg/1.7 mL (90 mg/mL) in a single-dose vial 

Patients should be hospitalized for 48 hours after administration of all doses within the TECVAYLI step-up dosing schedule.

 • Administer pretreatment medications as recommended. 

• See Full Prescribing Information for instructions on preparation and administration.

DOSAGE FORMS AND STRENGTHS-

 Injection • 30 mg/3 mL (10 mg/mL) in a single-dose vial                                                      • 153 mg/1.7 mL (90 mg/mL) in a single-dose vial 

PATIENT COUNSELING INFORMATION -

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Cytokine Release Syndrome (CRS)-                                                                         Discuss the signs and symptoms associated with CRS, including fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes.

Advise patients to immediately contact their healthcare provider if they experience any signs or symptoms of CRS.

Advise patients that they will be hospitalized for 48 hours after administration of all doses within the TECVAYLI step-up dosing schedule

Neurologic Toxicity including ICANS-                                                                     Discuss the signs and symptoms associated with neurologic toxicity, including ICANS, including headache, confusion, dysgraphia, motor dysfunction, neuropathy, or encephalopathy.

Advise patients to immediately contact their healthcare provider if they experience any signs or symptoms of neurologic toxicity.

Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI step-up dosing schedule and in the event of new onset of any neurologic toxicity symptoms until neurologic toxicity resolves.

TECVAYLI REMS TECVAYLI is available only through a restricted program called TECVAYLI REMS. Inform patients that they will be given a TECVAYLI Patient Wallet Card that they should carry with them at all times and show to all of their healthcare providers.

This card describes signs and symptoms of CRS and neurologic toxicity which, if experienced, should prompt the patient to immediately seek medical attention.

Hepatotoxicity-                                                                                                         Advise patients that liver enzyme elevations may occur and that they should report symptoms that may indicate liver toxicity, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice.

Infections-                                                                                                                          Discuss the signs and symptoms of infection.

Neutropenia-                                                                                                             Discuss the signs and symptoms associated with neutropenia and febrile neutropenia 

Hypersensitivity and Other Administration Reactions-                                             Advise patients to immediately seek medical attention for any signs and symptoms of systemic administration-related reactions.

Advise patients that local injection-site reactions may occur and to report any severe reactions 

Embryo-Fetal Toxicity -                                                                                           Advise pregnant women to inform their healthcare provider if they are pregnant or become pregnant.

Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment with TECVAYLI and for 5 months after the last dose.

Lactation-                                                                                                                      Advise women not to breastfeed during treatment with TECVAYLI and for 5 months after the last dose.

Manufactured by: Janssen Biotech, Inc. Horsham, PA 19044 U.S. License Number 1864 © 2022 Janssen Pharmaceutical Companies For patent information: www.janssenpatents.com

CLINICAL PHARMACOLOGY

1. Mechanism of Action-                                                                                           Teclistamab-cqyv is a bispecific T-cell engaging antibody that binds to the CD3 receptor expressed on the surface of T-cells and B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells.         

2.Pharmacokinetics-                                                                                                           The Cmax and AUCtau of teclistamab-cqyv after the first subcutaneous treatment dose increase proportionally over a dosage range of 0.08 mg/kg to 3 mg/kg (0.05 to 2 times the approved recommended treatment dosage).

Ninety percent of steady state exposure was achieved after 12 weekly treatment doses.

Table 12: Pharmacokinetic Parameters of Teclistamab-cqyv for the 13th Treatment Dose of 1.5 mg/kga Pharmacokinetic Parameter Teclistamab-cqyv Geometric Mean (CV%) Cmax (mcg/mL) 23.8 (55%) Ctrough (mcg/mL) 21.1 (63%) AUCtau (mcg·h/mL) 3,838 (57%) SD = standard deviation; Cmax = Maximum serum teclistamab-cqyv concentration; Ctrough = Serum teclistamab-cqyv concentration prior to next dose; CV = geometric coefficient of variation; AUCtau = Area under the concentration-time curve over the weekly dosing interval. a Following administration of teclistamab-cqyv in patients with relapsed or refractory multiple myeloma (MajesTEC-1).

Absorption-                                                                                                                   The mean bioavailability of teclistamab-cqyv was 72% when administered subcutaneously. The median (range) Tmax of teclistamab-cqyv after the first and 13th treatment doses were 139 (19 to 168) hours and 72 (24 to 168) hours, respectively.

Distribution-                                                                                                                  The mean (co

Elimination-                                                                                                                Teclistamab-cqyv clearance decreases over time, with a mean (CV%) maximal reduction from baseline to the 13th treatment dose of 40.8% (56%). The geometric mean (CV%) clearance is 0.472 L/day (64%) at the 13th treatment dose.

Patients who discontinue teclistamab-cqyv after the 13th treatment dose are expected to have a 50% reduction from Cmax in teclistamab-cqyv concentration at a median (5th to 95th percentile) time of 15 (7 to 33) days after Tmax and a 97% reduction from Cmax in teclistamab-cqyv concentration at a median time of 69 (32 to 163) days after Tmax.

Specific Populations- The volume of distribution and clearance of teclistamab-cqyv increase with increasing body weight (41 kg to 139 kg).

There were no clinically significant differences in the pharmacokinetics of teclistamab-cqyv based on age (24 to 84 years), sex, race (White, Black or African American), ethnicity (Hispanic/Latino, not Hispanic/Latino), mild or moderate renal impairment (estimated glomerular filtration rate Reference ID: 5066150 23 [eGFR] by Modification of Diet in Renal Disease [MDRD] method: 30 to 89 mL/min), or mild hepatic impairment (total bilirubin less than or equal to upper limit of normal [ULN] with AST greater than ULN or total bilirubin greater than 1 to 1.5 times ULN with any AST).

The effects of severe renal impairment (eGFR less than 30 mL/min) or moderate to severe hepatic impairment (total bilirubin greater than 1.5 times ULN with any AST) on the pharmacokinetics of teclistamabcqyv are unknown.

Drug Interaction Studies-                                                                                              No clinical studies evaluating the drug interaction potential of teclistamab-cqyv have been conducted..

 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 teclistamab-cqyv or of other teclistamab products.

During treatment in MajesTEC-1 (up to 27 months), 1/186 (0.5%) of patients treated with subcutaneous TECVAYLI at various dosages developed anti-teclistamab-cqyv antibodies.

Because of the low occurrence of anti-drug antibodies, the effect of these antibodies on the pharmacokinetics, pharmacodynamics, safety, and/or effectiveness of teclistamab products is unknown.

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary-                                                                                       Based on the mechanism of action, TECVAYLI may cause fetal harm when administered to a pregnant woman

 There are no available data on the use of TECVAYLI in pregnant women.

Advise women of the potential risk to the fetus. TECVAYLI is associated with hypogammaglobulinemia, therefore, assessment of immunoglobulin levels in newborns of mothers treated with TECVAYLI should be considered.

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 teclistamab-cqyv in human milk, the effect on the breastfed child, or the effects on milk production. Maternal IgG is known to be present in human milk.

The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to TECVAYLI are unknown.

Because of the potential for serious adverse reactions in a breastfed child, advise patients not to breastfeed during treatment with TECVAYLI and for 5 months after the last dose.

3. Females and Males of Reproductive Potential-                                                    TECVAYLI may cause fetal harm when administered to a pregnant woman.

Pregnancy Testing-                                                                                                          Verify pregnancy status of females of reproductive potential prior to initiating TECVAYLI.

Contraception -                                                                                                      Females -                                                                                                                           Advise females of reproductive potential to use effective contraception during treatment and for 5 months after the last dose of TECVAYLI.

4. Pediatric Use-                                                                                                                  The safety and efficacy of TECVAYLI have not been established in pediatric patients. 

5. Geriatric Use-                                                                                                              Of the 165 patients with relapsed or refractory multiple myeloma treated with TECVAYLI in MajesTEC-1 at the recommended

dosage, 48% were 65 years of age or older, and 15% were 75 years of age or older. No overall differences in safety or effectiveness were observed between patients 65 to 74 years of age compared to younger patients.

There is an insufficient number of patients 75 years of age or older to assess whether there are differences in safety or effectiveness.