Isatuximab

FDA Drug Information • Also known as: Sarclisa

Brand Names: Sarclisa
Dosage Form: LIQUID
Product Type: DRUG FOR FURTHER PROCESSING

Description

11 DESCRIPTION Isatuximab-irfc, a CD38-directed cytolytic antibody, is a chimeric immunoglobulin G1 (IgG1) monoclonal antibody (mAb). Isatuximab-irfc is produced from a mammalian cell line (Chinese hamster ovary, CHO) using a fed-batch production process. Isatuximab-irfc is composed of two identical immunoglobulin kappa light chains and two identical immunoglobulin gamma heavy chains and has an overall molecular weight of approximately 148 kDa. SARCLISA (isatuximab-irfc) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution, essentially free of visible particles in a single-dose vial for intravenous use. Each vial contains either 100 mg/5 mL or 500 mg/25 mL of isatuximab-irfc at a concentration of 20 mg/mL with a pH of 6.0. Each mL of solution contains 20 mg isatuximab-irfc, histidine (1.46 mg), histidine hydrochloride monohydrate (2.22 mg), polysorbate 80 (0.2 mg), sucrose (100 mg), and water for injection.

What Is Isatuximab Used For?

1 INDICATIONS AND USAGE SARCLISA is indicated: in combination with pomalidomide and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor. in combination with carfilzomib and dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy. in combination with bortezomib, lenalidomide, and dexamethasone, for the treatment of adult patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT). SARCLISA is a CD38-directed cytolytic antibody indicated: in combination with pomalidomide and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor. in combination with carfilzomib and dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy. in combination with bortezomib, lenalidomide and dexamethasone, for the treatment of adult patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT). ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Premedicate with dexamethasone, acetaminophen, H2 antagonists, and diphenhydramine. ( 2.2 ) The recommended dosage of SARCLISA is 10 mg/kg as an intravenous infusion. See full prescribing information for SARCLISA schedules of administration and drugs used in combination. ( 2.1 ) 2.1 Recommended Dosage Administer pre-infusion medications [see Dosage and Administration (2.2) ] . SARCLISA should be administered by a healthcare professional, with immediate access to emergency equipment and appropriate medical support to manage infusion-related reactions if they occur [see Warnings and Precautions (5.1) ] . The recommended dose of SARCLISA is 10 mg/kg actual body weight administered as an intravenous infusion in combination with pomalidomide and dexamethasone or in combination with carfilzomib and dexamethasone, or in combination with bortezomib, lenalidomide, and dexamethasone. SARCLISA dosing schedules are provided in Tables 1 and 2 [see Clinical Studies (14) ] . Table 1: SARCLISA Dosing Schedule in Combination with Pomalidomide and Dexamethasone or in Combination with Carfilzomib and Dexamethasone Cycles Dosing schedules Cycle 1 (28-day cycle) Days 1, 8, 15, and 22 (weekly) Cycle 2 and beyond (28-day cycles) Days 1, 15 (every 2 weeks) Table 2: SARCLISA Dosing Schedule in Combination with Bortezomib, Lenalidomide, and Dexamethasone Cycles Dosing schedules Cycle 1 (42-day cycle) Days 1, 8, 15, 22, and 29 Cycles 2 to 4 (42-day cycles) Days 1, 15, and 29 (every 2 weeks) Cycles 5 to 17 (28-day cycles) Days 1 and 15 (every 2 weeks) Cycles 18 and beyond (28-day cycles) Day 1 (every 4 weeks) Treatment is repeated until disease progression or unacceptable toxicity. SARCLISA is used in combination with pomalidomide and dexamethasone or in combination with carfilzomib and dexamethasone or in combination with bortezomib, lenalidomide, and dexamethasone. For dosing instructions of combination agents administered with SARCLISA, see Clinical Studies (14) and manufacturer's prescribing information. Missed SARCLISA Doses If a planned dose of SARCLISA is missed, administer the dose as soon as possible and adjust the treatment schedule accordingly, maintaining the treatment interval. 2.2 Recommended Premedications and Antimicrobial Prophylaxis Recommended Premedications Administer the following premedications prior to SARCLISA infusion to reduce the risk and severity of infusion-related reactions [see Warnings and Precautions (5.1) ] : When administered in combination with SARCLISA and pomalidomide: Dexamethasone 40 mg orally or intravenously (or 20 mg orally or intravenously for patients ≥75 years of age). When administered in combination with SARCLISA and carfilzomib: Dexamethasone 20 mg (intravenously on the days of SARCLISA and/or carfilzomib infusions, orally on day 22 in cycle 2 and beyond, and orally on day 23 in all cycles). When administered in combination with SARCLISA, bortezomib, and lenalidomide: Dexamethasone 20 mg...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions from SARCLISA are also described in other sections of the labeling: Infusion-Related Reactions [see Warnings and Precautions (5.1) ] Infections [see Warnings and Precautions (5.2) ] Neutropenia [see Warnings and Precautions (5.3) ] Second Primary Malignancies [see Warnings and Precautions (5.4) ] In combination with pomalidomide and dexamethasone : The most common adverse reactions (≥20%) are upper respiratory tract infection, infusion-related reactions, pneumonia, and diarrhea. The most common hematology laboratory abnormalities (≥80%) are decreased hemoglobin, decreased neutrophils, decreased lymphocytes, and decreased platelets. ( 6.1 ) In combination with carfilzomib and dexamethasone : The most common adverse reactions (≥20%) are upper respiratory tract infection, infusion-related reactions, fatigue, hypertension, diarrhea, pneumonia, dyspnea, insomnia, bronchitis, cough, and back pain. The most common hematology laboratory abnormalities (≥80%) are decreased hemoglobin, decreased lymphocytes, and decreased platelets. ( 6.1 ) In combination with bortezomib, lenalidomide and dexamethasone : The most common adverse reactions (≥20%) are upper respiratory tract infections, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reaction, insomnia, and COVID-19. The most common hematologic laboratory abnormalities (≥80%) are decreased hemoglobin, decreased leukocytes, decreased lymphocytes, decreased platelets, and decreased neutrophils. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact sanofi-aventis U.S. LLC at 1-800-633-1610 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 a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Relapsed and/or Refractory Multiple Myeloma Combination treatment with pomalidomide and dexamethasone (Isa-Pd) The safety of SARCLISA was evaluated in ICARIA-MM, a randomized, open-label clinical trial in patients with previously treated multiple myeloma. Patients received SARCLISA 10 mg/kg intravenously, weekly in the first cycle and every two weeks thereafter, in combination with pomalidomide and dexamethasone (Isa-Pd) (n=152) or pomalidomide and dexamethasone (Pd) (n=149) [see Clinical Studies (14) ] . Among patients receiving Isa-Pd, 66% were exposed to SARCLISA for 6 months or longer and 24% were exposed for greater than 12 months or longer. Serious adverse reactions occurred in 62% of patients receiving Isa-Pd. Serious adverse reactions in >5% of patients who received Isa-Pd included pneumonia (26%), upper respiratory tract infections (7%), and febrile neutropenia (7%). Fatal adverse reactions occurred in 11% of patients (those that occurred in more than 1% of patients were pneumonia and other infections [3%]). Permanent treatment discontinuation due to an adverse reaction (grades 1–4) occurred in 7% of patients who received Isa-Pd. The most frequent adverse reactions requiring permanent discontinuation in patients who received Isa-Pd were infections (2.6%). SARCLISA alone was discontinued in 3% of patients due to infusion-related reactions. Dosage interruptions due to an adverse reaction occurred in 31% of patients who received SARCLISA. The most frequent adverse reaction requiring dosage interruption was infusion-related reaction (28%). The most common adverse reactions (≥20%) were upper respiratory tract infection, infusion-related reactions, pneumonia, and diarrhea. Table 4 summarizes the adverse reactions in ICARIA-MM. Table 4: Adverse Reactions (≥10%) in Patients Receiving SARCLISA, Pomalidomide, and Dexamethasone with a Difference Between Arms of ≥5% Compared to Control Arm in...

Drug Interactions

7 DRUG INTERACTIONS 7.1 Laboratory Test Interference Interference with Serological Testing SARCLISA, an anti-CD38 antibody, may interfere with blood bank serologic tests with false positive reactions in indirect antiglobulin tests (indirect Coombs tests), antibody detection (screening) tests, antibody identification panels, and antihuman globulin crossmatches in patients treated with SARCLISA [see Warnings and Precautions (5.5) ] . Interference with Serum Protein Electrophoresis and Immunofixation Tests SARCLISA may be incidentally detected by serum protein electrophoresis and immunofixation assays used for the monitoring of M-protein and may interfere with accurate response classification based on International Myeloma Working Group (IMWG) criteria [see Warnings and Precautions (5.5) ] . In patients with persistent very good partial response, where interference is suspected, consider using an FDA-cleared isatuximab-irfc-specific IFE assay to distinguish isatuximab from any remaining endogenous M protein in the patient's serum to facilitate determination of a complete response.

Contraindications

4 CONTRAINDICATIONS SARCLISA is contraindicated in patients with severe hypersensitivity to isatuximab-irfc or to any of its excipients [see Warnings and Precautions (5.1) ] . Patients with severe hypersensitivity to isatuximab-irfc or to any of its excipients. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary SARCLISA can cause fetal harm when administered to a pregnant woman. The assessment of isatuximab-irfc-associated risks is based on the mechanism of action and data from target antigen CD38 knockout animal models (see Data ). There are no available data on SARCLISA use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Animal reproduction toxicity studies have not been conducted with isatuximab-irfc. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, miscarriage, 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. The combination of SARCLISA and pomalidomide or lenalidomide is contraindicated in pregnant women because pomalidomide and lenalidomide may cause birth defects and death of the unborn child. Refer to the pomalidomide or lenalidomide prescribing information on use during pregnancy. Pomalidomide and lenalidomide are only available through a REMS program. Clinical Considerations Fetal/neonatal reactions Immunoglobulin G1 monoclonal antibodies are known to cross the placenta. Based on its mechanism of action, SARCLISA may cause depletion of fetal CD38-positive immune cells and decreased bone density. Defer administration of live vaccines to neonates and infants exposed to SARCLISA in utero until a hematology evaluation is completed. Data Animal data Mice that were genetically modified to eliminate all CD38 expression (CD38 knockout mice) had reduced bone density which recovered 5 months after birth. Data from studies using CD38 knockout animal models also suggest the involvement of CD38 in regulating humoral immune responses (mice), feto-maternal immune tolerance (mice), and early...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied SARCLISA (isatuximab-irfc) injection is a clear to slightly opalescent, colorless to slightly yellow solution, essentially free of visible particulates, supplied as follows: One 100 mg/5 mL (20 mg/mL) single-dose vial in a carton: NDC 0024-0654-01 One 500 mg/25 mL (20 mg/mL) single-dose vial in a carton: NDC 0024-0656-01 Storage Store in a refrigerator at 36°F to 46°F (2°C to 8°C) in the original carton to protect from light. Do not freeze. Do not shake. Handling and Disposal Discard unused portion of solution. All materials that have been utilized for dilution and administration should be disposed of according to standard procedures.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.