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is indicated: in combination with pomalidomide and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least 1 prior line of therapy 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 ESCENA 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 1 prior line of therapy 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 )

and intravenous isatuximab-irfc have different dosage and route of administration instructions. Administer SARCLISA ESCENA only as a subcutaneous injection. Premedicate with dexamethasone, leukotriene receptor antagonist, acetaminophen, and diphenhydramine. ( 2.2 ) The recommended dosage of SARCLISA ESCENA is 1,400 mg administered as subcutaneous injection with the CirCLIQ™ On-Body Delivery System (OBDS) or with a syringe and infusion set for manual administration. See full prescribing information for SARCLISA ESCENA schedules of administration and drugs used in combination. ( 2.1 ) 2.1 Important Dosage Information SARCLISA ESCENA and intravenous isatuximab-irfc have different dosage and administration instructions [see Dosage and Administration (2.2) ] . SARCLISA ESCENA is for subcutaneous use only. Check the product label to ensure that the correct formulation (SARCLISA ESCENA or intravenous isatuximab-irfc) is being prescribed and administered. 2.2 Recommended Dosage Administer premedications before SARCLISA ESCENA administration [see Dosage and Administration (2.3) ] . SARCLISA ESCENA should be administered by a health care professional [see Warnings and Precautions (5.1) ] . Patients currently receiving intravenous isatuximab-irfc may transition to SARCLISA ESCENA solution for injection after the completion of the first cycle. The recommended dose of SARCLISA ESCENA is 1,400 mg administered as a subcutaneous injection with the CirCLIQ On-Body Delivery System (OBDS) or with a syringe and infusion set for manual administration, in combination with pomalidomide and dexamethasone or in combination with carfilzomib and dexamethasone, or in combination with bortezomib, lenalidomide, and dexamethasone. SARCLISA ESCENA dosing schedules are provided in Tables 1 and 2 [see Clinical Studies (14) ] . Table 1: SARCLISA ESCENA 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 and 15 (every 2 weeks) Table 2: SARCLISA ESCENA Dosing Schedule in Combination with Bortezomib, Lenalidomide, and Dexamethasone Cycles Dosing schedule Cycle 1 (28-day cycle) Days 1, 8, 15, 22 (weekly) Cycles 2 to 12 (28-day cycles) Days 1 and 15 (every 2 weeks) Cycles 13 and beyond (28-day cycles) Day 1 (every 4 weeks) Treatment is repeated until disease progression or unacceptable toxicity. SARCLISA ESCENA 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 ESCENA, see Clinical Studies (14) and manufacturer's prescribing information. Missed SARCLISA ESCENA Doses If a planned dose of SARCLISA ESCENA is missed, administer the dose as soon as possible and adjust the treatment schedule accordingly, maintaining the treatment interval. 2.3 Recommended Premedications and Antimicrobial Prophylaxis Recommended Premedications Administer the following premedications 15 to 60 minutes prior to SARCLISA ESCENA administration to reduce the risk and severity of systemic administration reactions [see Warnings and Precautions (5.1) ] : When administered in combination with SARCLISA ESCENA and pomalidomide: Dexamethasone 40 mg orally or intravenously (or 20 mg orally or intravenously for patients 75 years of age or older). When administered in combination with SARCLISA ESCENA and carfilzomib: Dexamethasone 20 mg orally or intravenously. When administered in combination with SARCLISA ESCENA, bortezomib, and lenalidomide: Dexamethasone 20 mg orally. Leukotriene receptor antagonist, at cycle 1 only (Days 1, 8, 15, and 22). Acetaminophen 650 mg to 1,000 mg orally. Diphenhydramine 25 mg to 50 mg orally or intravenously (or equivalent). The intravenous route of diphenhydramine is preferred for at least the first 4 administrations of SARCLISA ESCENA. The above recommended dose of dexamethasone (orally or intravenously) corresponds to the total dose to be administered before SARCLISA ESCENA administration as part of the premedication and part of the backbone treatment [see Clinical Studies (14) ]. If no systemic administration reaction occurs during Cycle 1, assess patient specific factors and consider omitting subsequent premedication during future treatment cycles. Recommended Antimicrobial Prophylaxis Initiate antibacterial and antiviral prophylaxis (such as herpes zoster prophylaxis) if needed based on standard guidelines [see Warnings and Precautions (5.2 , 5.3) ] . 2.4 Dosage Modifications for Adverse Reactions No dose reduction of SARCLISA ESCENA is recommended. Dose delay or omission may be required [see Warnings and Precautions (5.1 , 5.2) ] . 2.5 Preparation SARCLISA ESCENA is only for abdominal subcutaneous administration using: CirCLIQ On-Body Delivery System (OBDS ) OR 20 mL syringe and infusion set (manual administration using commercially available syringe and infusion set). SARCLISA ESCENA should be administered by a healthcare provider. To prevent medication errors, check SARCLISA ESCENA vial label to ensure it is the correct medication for subcutaneous use (vial with green cap). Do not administer SARCLISA ESCENA intravenously. SARCLISA ESCENA is ready to use and should not be diluted. Prepare and administer SARCLISA ESCENA subcutaneously using clean technique. Prior to use‚ allow SARCLISA ESCENA to reach ambient temperature between 18°C to 28°C (64°F to 82°F) for approximately 20 minutes. Keep the unpunctured vial in the original carton prior to use to protect from light. Do not heat. Do not shake. Once the vial has been taken out of the refrigerator, it must not be returned to the refrigerator. Unpunctured vials may be stored at ambient temperature between 18°C to 28°C (64°F to 82°F) for a single period of up to 24 hours. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. The solution may contain a few translucent to white particles. SARCLISA ESCENA should not be used if the solution is cloudy or discolored, or if particles other than those described above are present [see Dosage Forms and Strengths (3) ] . Preparation with CirCLIQ On-Body Delivery System Refer to the Instructions for Use for CirCLIQ OBDS provided with the device for full preparation and administration information. Once the vial is punctured, the injection with the CirCLIQ On-Body Injector should be performed as soon as possible. If the injection is not completed within 4 hours, discard the vial and the On-Body Delivery System. Preparation with syringe and infusion set for manual administration Before you begin, collect your supplies: The syringe must be a 20 mL polypropylene syringe with Luer-fitting connector. The transfer needle with filter must be made of 18G stainless steel with 5-micron filter and Luer-fitting connector. The subcutaneous infusion set must have a 23G stainless steel needle for administration and tubing up to 12 inches (30 cm) length made of polyethylene, or polyvinyl chloride (PVC), with a Luer-fitting connector. Check the expiration date. Remove green vial cap and wipe vial rubber stopper with an alcohol wipe and allow to air dry. Attach the transfer needle with 5-micron filter to the syringe and fill the syringe. Withdraw the full content of the SARCLISA ESCENA vial into a 20 mL compatible syringe. Note: if the syringe containing SARCLISA ESCENA is not used immediately: Remove the transfer needle with filter. Attach a syringe closing cap to the syringe. Label the syringe with the SARCLISA ESCENA peel-off label provided in the vial carton and as per institutional standards. Store it for up to 4 hours at room temperature between 15°C to 25°C (59°F to 77°F) and ambient light, including the administration time. Discard after 4 hours, if not used. Attach the subcutaneous infusion set to the syringe. Prime the syringe and subcutaneous infusion set with SARCLISA ESCENA. Note: To avoid needle clogging, attach the subcutaneous infusion set to the syringe immediately prior to injection. 2.6 Administration On the days when both SARCLISA ESCENA and carfilzomib are administered, administer dexamethasone first, followed by SARCLISA ESCENA administration, then followed by carfilzomib infusion. SARCLISA ESCENA is only for abdominal subcutaneous administration. Data are only available with an injection performed into the abdomen. Change (rotate) the site of each subcutaneous administration – at least 1 inch (2.5 cm) from previous injection site - with every injection to avoid accumulation of fatty tissue. Do not inject other medications in the area where SARCLISA ESCENA is injected. Do not inject into areas where the skin is injured, tender, red, hot, has scars, or is excessively hairy. Administration with CirCLIQ On-Body Delivery System Refer to the Instructions for Use for CirCLIQ OBDS provided with the device for full preparation and administration information. Do not inject other medications in the area where SARCLISA ESCENA is injected. Administration with syringe and infusion set for manual administration Prepare injection site and insert needle. Wipe injection site with an alcohol swab and allow it to dry. Avoid injecting within 2 inches (5 cm) around the belly button. Remove protective needle cover. Pinch skin at the injection site on the abdomen. It is important to pinch enough skin to inject under the skin and not into the muscle. Insert needle at a 45-degree angle with a quick, dart-like motion. Note: Try to limit needle and syringe movement during the injection. If needed, secure the subcutaneous infusion set in place with a bandage. Inject 10 mL of SARCLISA ESCENA subcutaneously into the abdomen, over approximately 6 minutes. Pause or slow down delivery rate if the patient experiences pain. In the event pain is not alleviated by pausing or slowing down delivery rate, a second injection site may be chosen on the opposite side of the abdomen to deliver the remainder of the dose.

Hypersensitivity and Other Administration Reactions: In case of grade ≥2 systemic administration reaction (SAR), interrupt SARCLISA ESCENA and manage medically. In case of grade 4 SAR, permanently discontinue SARCLISA ESCENA. ( 5.1 ) Neutropenia : Monitor complete blood cell counts periodically during treatment. Monitor patients with neutropenia for signs of infection. SARCLISA ESCENA dose delays and the use of colony-stimulating factor may be required to allow improvement of neutrophil count. ( 5.2 ) Infections : SARCLISA ESCENA may cause serious and fatal infections. Monitor patients for signs and symptoms of infection and treat appropriately. ( 5.3 ) Second Primary Malignancies (SPM) : Monitor patients for the development of second primary malignancies. ( 5.4 ) Laboratory Test Interference : Interference with Serological Testing (Indirect Antiglobulin Test): Type and screen patients prior to starting treatment. Inform blood banks that a patient has received isatuximab-irfc. ( 5.5 , 7.1 ) Interference with Serum Protein Electrophoresis and Immunofixation Tests: isatuximab-irfc may interfere with the assays used to monitor M-protein, which may impact the determination of complete response. ( 5.5 , 7.1 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.6 , 8.1 , 8.3 ) 5.1 Hypersensitivity and Other Administration Reactions SARCLISA ESCENA can cause both systemic administration-related reactions (SARs), including severe or life-threatening reactions, and local injection-site reactions. Systemic Administration Reactions In a pooled safety population of 411 patients with multiple myeloma who received SARCLISA ESCENA in combination with pomalidomide and dexamethasone (Pd), with carfilzomib and dexamethasone (Kd), and with bortezomib, lenalidomide, and dexamethasone (VRd) (IRAKLIA, IZALCO, and IsaSoCut, respectively, N=411), SARs occurred in 3.2% (Grade 1: 2.2%, Grade 2: 0.7%, Grade 3: 0.2%) of patients. SARs occurred at the first administration in 1.9% of patients and at subsequent administrations in 1.5% of patients. The median time to onset was 4 hours (range: 12 minutes to 3 days). The most frequently reported symptoms of SARs (all below 1%) were pyrexia and dyspnea, and Grade ≥3 symptoms was dyspnea (not collected in IsaSoCut study) [see Dosage and Administration (2.3) and Adverse Reactions (6.1) ] . In multiple myeloma clinical trials with intravenous isatuximab-irfc, anaphylactic reactions occurred in <1% of patients. To decrease the risk and severity of SARs, premedicate patients prior to SARCLISA ESCENA administration with leukotriene receptor antagonists (at cycle 1 only), acetaminophen, diphenhydramine, or equivalent, and dexamethasone [see Dosage and Administration (2.2) ] . In case of grade 2 SAR during SARCLISA ESCENA administration, stop current administration and do not complete it. Administer additional premedication, as needed, for subsequent SARCLISA ESCENA administration. In case of grade 3 SAR during SARCLISA ESCENA administration, stop current administration and do not complete it. SARCLISA ESCENA administration may be resumed at the next planned administration. In case of a third occurrence of a grade 3 SAR, permanently discontinue SARCLISA ESCENA treatment. In case of grade 4 SAR, permanently discontinue SARCLISA ESCENA treatment. Injection Site Reactions In clinical trials of SARCLISA ESCENA in combination with Pd, Kd, or VRd (IRAKLIA, IZALCO, and IsaSoCut, respectively, N=411), injection site reactions (ISRs) with SARCLISA ESCENA administration were reported in 9% (8% Grade 1 and 1.5% Grade 2) of patients and in 0.86% of injections. Among the SARCLISA ESCENA injections with ISRs, 82% occurred the day of the administration and 4.2% were delayed by at least 3 days. With SARCLISA ESCENA-Pd and SARCLISA ESCENA-Kd, 5% of patients experienced symptoms of ISR (not collected in IsaSoCut study). The most frequent (≥1%) symptoms of ISR were injection site erythema (3.3%), injection site swelling (2.1%), and injection site pain (1.5%). In case of grade 2 ISR during administration of SARCLISA ESCENA, interrupt it and resume it only after recovery to grade ≤1 with pauses during the administration (if using OBDS) or a slower administration (if manual injection). If the Grade 2 ISR occurs after the administration, continue SARCLISA ESCENA treatment after recovery to grade ≤1. In case of grade 3 or 4 ISR, permanently discontinue SARCLISA ESCENA treatment. In case SARCLISA ESCENA administration using CirCLIQ OBDS needs to be paused, please refer to the OBDS Instruction For Use (IFU). 5.2 Neutropenia Neutropenia was reported in patients receiving SARCLISA ESCENA subcutaneously in combination with Pd, Kd, or VRd. In clinical trials of SARCLISA ESCENA (IRAKLIA, IZALCO, and IsaSoCut, N=411), neutropenia occurred in 86% of patients based on laboratory value. Grade 3–4 neutropenia occurred in 66% of patients based on laboratory value. Febrile neutropenia was reported in 3.4% and neutropenic infections occurred in 13% of patients [see Adverse Reactions (6.1) ] . Monitor complete blood cell counts periodically during treatment. Monitor patients with neutropenia for signs of infection. In case of grade 4 neutropenia, delay or omit SARCLISA ESCENA dose until neutrophil count recovery to at least 1 × 10 9 /L, and provide supportive care with growth factors, according to institutional guidelines [see Dosage and Administration (2.3) ] . 5.3 Infections SARCLISA ESCENA can cause severe, life-threatening, or fatal infections. In patients who received SARCLISA ESCENA subcutaneously in combination with Pd, Kd, or VRd (IRAKLIA, IZALCO, and IsaSoCut, respectively, N=411), fatal infections occurred in 2.9% of patients, serious infections occurred in 29% of patients, and Grade ≥3 infections in 29% of patients. The most commonly reported infections (≥10%) were pneumonia (21%), upper respiratory tract infection (19%), and Covid-19 (12%). The most frequent serious infection (≥5%) was pneumonia (17%) [see Adverse Reactions (6.1) ]. Patients receiving SARCLISA ESCENA should be closely monitored for signs of infection and appropriate standard therapy instituted. Antibacterial and antiviral prophylaxis (such as herpes zoster prophylaxis) should be considered during treatment [see Dosage and Administration (2.3) ] . 5.4 Second Primary Malignancies Second primary malignancies were reported in 3.9% of patients in clinical trials with SARCLISA ESCENA in combination with Pd, Kd, and VRd (IRAKLIA, IZALCO, and IsaSoCut, respectively, N=411). Monitor patients for the development of second primary malignancies and initiate treatment as indicated. 5.5 Laboratory Test Interference Interference with Serological Testing (Indirect Antiglobulin Test) Isatuximab-irfc binds to CD38 on red blood cells (RBCs) and may result in a false positive indirect antiglobulin test (indirect Coombs test). This interference with the indirect Coombs test may persist for at least 6 months after the last administration of intravenous isatuximab-irfc. The indirect antiglobulin test was positive during intravenous isatuximab-irfc-Pd treatment in 68% of the tested patients, and during intravenous isatuximab-irfc-Kd treatment in 63% of patients. In patients with a positive indirect antiglobulin test, blood transfusions were administered without evidence of hemolysis. ABO/RhD typing was not affected by intravenous isatuximab-irfc treatment. Before the first isatuximab-irfc administration, conduct blood type and screen tests on isatuximab-treated patients. Consider phenotyping prior to starting isatuximab-irfc treatment. If treatment with isatuximab-irfc has already started, inform the blood bank that the patient is receiving isatuximab-irfc and isatuximab-irfc interference with blood compatibility testing can be resolved using dithiothreitol-treated RBCs. If an emergency transfusion is required, non–cross-matched ABO/RhD-compatible RBCs can be given as per local blood bank practices [see Drug Interactions (7.1) ] . Interference with Serum Protein Electrophoresis and Immunofixation Tests Isatuximab-irfc is an IgG kappa monoclonal antibody that can be incidentally detected on both serum protein electrophoresis and immunofixation assays (IFE) used for the clinical monitoring of endogenous M-protein. In patients with persistent very good partial response, where interference is suspected, consider using a validated isatuximab-specific IFE assay (Sebia Hydrashift) to remove isatuximab-irfc interference and specifically visualize any remaining serum M-protein, to facilitate determination of complete response. [see Drug Interactions (7.1) ] . 5.6 Embryo-Fetal Toxicity Based on its mechanism of action, isatuximab-irfc can cause fetal harm when administered to a pregnant woman. Isatuximab-irfc may cause fetal immune cell depletion and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with isatuximab-irfc and for 7 months after the last dose [see Use in Specific Populations (8.1 , 8.3) ] . The combination of isatuximab-irfc with pomalidomide or lenalidomide is contraindicated in pregnant women because pomalidomide or lenalidomide may cause birth defects and death of the unborn child. Refer to the pomalidomide or lenalidomide prescribing information on use during pregnancy.

7.1 Laboratory Test Interference Interference with Serological Testing Isatuximab-irfc, 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 isatuximab-irfc [see Warnings and Precautions (5.5) ] . Interference with Serum Protein Electrophoresis and Immunofixation Tests Isatuximab-irfc 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) ] . Because of this interference, Hydrashift assay was routinely used in IRAKLIA and IZALCO clinical studies for efficacy assessment to determine the complete response in patients with IgG kappa myeloma protein. 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-irfc from any remaining endogenous M-protein in the patient's serum to facilitate determination of a complete response.

The following clinically significant adverse reactions from SARCLISA ESCENA are also described in other sections of the labeling: Hypersensitivity and Other Administration Reactions [see Warnings and Precautions (5.1) ] Neutropenia [see Warnings and Precautions (5.2) ] Infections [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, fatigue, pneumonia, musculoskeletal pain, and diarrhea. ( 6.1 ) In combination with carfilzomib and dexamethasone : The most common adverse reactions (≥20%) are upper respiratory tract infection and musculoskeletal pain. ( 6.1 ) In combination with bortezomib, lenalidomide and dexamethasone : The most common adverse reactions (≥20%) are peripheral neuropathy, constipation, diarrhea, fatigue, musculoskeletal pain, upper respiratory tract infections, injection site reaction, insomnia, edema, rash, and erythema. ( 6.1 ) The most common hematology laboratory abnormalities (≥40%) with SARCLISA ESCENA combination therapies are decreased neutrophils, decreased platelets, decreased hemoglobin, decreased leukocytes, and decreased lymphocytes. ( 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 (SARCLISA ESCENA-Pd versus intravenous isatuximab-irfc-Pd) IRAKLIA The safety of SARCLISA ESCENA was evaluated in IRAKLIA, a randomized, open-label phase 3 clinical trial in patients with previously treated multiple myeloma. Patients received SARCLISA ESCENA 1,400 mg administered subcutaneously, weekly in the first cycle and every two weeks thereafter, in combination with pomalidomide and dexamethasone (SARCLISA ESCENA-Pd, n=263) or isatuximab-irfc administered intravenously in combination with pomalidomide and dexamethasone (intravenous isatuximab-irfc-Pd, n=264) [see Clinical Studies (14) ] . Among patients receiving SARCLISA ESCENA-Pd, 66% were exposed to SARCLISA ESCENA for 6 months or longer and 25% were exposed for greater than 12 months or longer. The median duration of the injection with OBDS was 13 minutes. Serious adverse reactions occurred in 53% of patients receiving SARCLISA ESCENA-Pd. Serious adverse reactions in ≥5% of patients who received SARCLISA ESCENA-Pd included pneumonia (20.5%). Fatal adverse reactions occurred in 4.9% of patients who received SARCLISA ESCENA-Pd, including pneumonia (1.5%), sepsis/septic shock (1.5%), death (0.8%), COVID-19, lower respiratory tract infection, hemorrhagic stroke, and sudden death (0.4% each). Permanent treatment discontinuation due to an adverse reaction occurred in 8% of patients who received SARCLISA ESCENA-Pd. Adverse reactions which resulted in permanent discontinuation of SARCLISA ESCENA-Pd in more than 1 patient included pneumonia, death, COVID-19, sepsis, anemia, and neutrophil count decreased. The most common adverse reactions (≥20%) were upper respiratory tract infection, fatigue, pneumonia, musculoskeletal pain, and diarrhea. The most common hematology laboratory abnormalities (≥40%) were decreased leukocytes, decreased neutrophils, decreased lymphocytes, decreased platelets, and decreased hemoglobin. Table 3 summarizes the adverse reactions in IRAKLIA. Table 3: Adverse Reactions (≥10%) in Patients Who Received SARCLISA ESCENA-Pd or Intravenous Isatuximab-irfc-Pd in IRAKLIA Adverse Reaction SARCLISA ESCENA-Pd (N=263) Intravenous isatuximab-irfc-Pd (N=264) All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Infections and infestations Upper respiratory tract infection Upper respiratory tract infection is a grouping of viral, bacterial, fungal, and pathogen unspecified infections. 39 4.2 37 3.4 Pneumonia Pneumonia is a grouping of pneumonia from viral, fungal, and bacterial origins. 27 Includes 5 patients (1.9%) with fatal pneumonia. 19 28 Includes 4 patients (1.5%) with fatal pneumonia. 20 COVID-19 COVID-19 is a grouping of Coronavirus infections. 14 Includes 1 patient (0.4%) with fatal COVID-19. 4.6 18 4.2 Musculoskeletal and connective tissue disorders Musculoskeletal pain Musculoskeletal pain includes: Arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, pain in extremity, and spinal pain. 23 2.3 24 3 Gastrointestinal disorders Diarrhea 20 4.6 20 0.8 Constipation 14 0 13 0 General disorders and administration site conditions Fatigue Fatigue includes: fatigue, asthenia, malaise 29 4.9 22 1.5 Edema peripheral 8 0 12 1.1 Systemic administration reaction 1.5 0.4 25 1.1 Psychiatric disorders Insomnia 15 2.7 15 4.5 Table 4 summarizes the laboratory abnormalities in IRAKLIA. Table 4: Laboratory Abnormalities That Worsened (≥30%) From Baseline in Patients Who Received SARCLISA ESCENA-Pd versus Intravenous Isatuximab-irfc-Pd in IRAKLIA Laboratory Abnormality SARCLISA ESCENA-Pd (N=263) Intravenous isatuximab-irfc-Pd (N=264) All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) The denominator used for the percentage calculation is the number of patients with at least 1 evaluation of the laboratory test during the considered observation period. Hematology Leukocytes decreased 98 62 90 56 Neutrophils decreased 97 85 93 74 Lymphocytes decreased 92 49 85 41 Platelets decreased 77 26 73 23 Hemoglobin decreased 56 13 47 13 Chemistry Calcium decreased 48 0.8 49 0.4 Magnesium decreased 43 0.4 47 0 Albumin decreased 40 1.9 39 1.9 Alanine aminotransferase increased 34 1.9 35 0.8 Sodium decreased 33 6 31 4.2 Creatinine increased 32 5 23 2.7 Alkaline phosphatase increased 30 0.8 26 0 Combination treatment with carfilzomib and dexamethasone (SARCLISA ESCENA-Kd) IZALCO The safety of SARCLISA ESCENA was evaluated in IZALCO, a randomized, open-label phase 2 clinical trial in patients with previously treated multiple myeloma. In IZALCO, patients received SARCLISA ESCENA 1,400 mg subcutaneously weekly in the first cycle, and every two weeks thereafter, in combination with carfilzomib and dexamethasone (SARCLISA ESCENA-Kd) (n=74). SARCLISA ESCENA was administered either by CirCLIQ OBDS or by manual administration [see Clinical Studies (14) ] . In IZALCO, 77% of patients were exposed to SARCLISA ESCENA for 6 months or longer and 7% were exposed for greater than 12 months. Serious adverse reactions occurred in 41% of patients receiving SARCLISA ESCENA-Kd. Serious adverse reactions in ≥5% of patients included pneumonia (11%). Fatal adverse reaction occurred in 5.4% of patients who received SARCLISA ESCENA-Kd, including meningitis (1.4%), acute pulmonary edema (1.4%), acute respiratory distress syndrome (1.4%), and death from unknown cause (1.4%). Permanent treatment discontinuation due to an adverse reaction occurred in 8% of patients who received SARCLISA ESCENA-Kd. Adverse reactions which resulted in permanent discontinuation of SARCLISA ESCENA-Kd in 1 patient each included lower respiratory tract infection, meningitis, acute pulmonary edema, acute respiratory distress syndrome, erythema multiforme, and death. The most common adverse reactions (≥20%) were upper respiratory tract infection and musculoskeletal pain. The most common hematology laboratory abnormalities (≥40%) were decreased platelets, decreased lymphocytes, decreased leukocytes, decreased hemoglobin, and decreased neutrophils. Table 5 summarizes the adverse reactions in IZALCO. Table 5: Adverse Reactions (≥10%) in Patients Who Received SARCLISA ESCENA-Kd in IZALCO SARCLISA ESCENA-Kd (N=74) Adverse Reaction All Grades (%) Grade 3 or 4 (%) Infections and infestations Upper respiratory tract infection Upper respiratory tract infection is a grouping of bacterial, viral, and pathogen unspecified infections. 54 1.4 Pneumonia Pneumonia is a grouping of pneumonia from fungal, viral, and pathogen unspecified origins. 18 10 COVID-19 12 0 Musculoskeletal and connective tissue disorders Musculoskeletal pain Musculoskeletal pain includes: Arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, pain in extremity, and spinal pain. 20 1.4 Vascular disorders Hypertension 14 4.1 Psychiatric disorders Insomnia 12 2.7 Gastrointestinal disorders Diarrhea 11 0 General disorders and administration site conditions Pyrexia 11 1.4 Clinically relevant adverse reactions in <10% of patients who received SARCLISA ESCENA in combination with carfilzomib and dexamethasone included cardiac failure. Table 6 summarizes the laboratory abnormalities in IZALCO. Table 6: Laboratory Abnormalities That Worsened (≥30%) From Baseline in Patients Who Received SARCLISA ESCENA-Kd in IZALCO Laboratory Abnormality SARCLISA ESCENA-Kd (N=74) All Grades (%) Grade 3 or 4 (%) The denominator used for the percentage calculation is the number of patients with at least 1 evaluation of the laboratory test during the considered observation period. Hematology Lymphocytes decreased 85 56 Platelets decreased 85 19 Leukocytes decreased 59 15 Hemoglobin decreased 56 14 Neutrophils decreased 47 15 Chemistry Calcium decreased 55 1.4 Sodium decreased 44 5 Magnesium decreased 33 0 Alkaline phosphatase increased 33 0 Albumin decreased 32 1.4 Newly Diagnosed Multiple Myeloma not Eligible for Autologous Stem Cell Transplant Combination treatment with bortezomib, lenalidomide, and dexamethasone (SARCLISA ESCENA-VRd) IsaSoCut The safety of SARCLISA ESCENA was evaluated in IsaSoCut, a multicenter, open-label single-arm, phase 2 clinical trial in patients with newly diagnosed multiple myeloma who are not eligible for stem cell transplantation. Patients received SARCLISA ESCENA 1,400 mg administered subcutaneously with CirCLIQ OBDS in combination with bortezomib, lenalidomide, and dexamethasone (SARCLISA ESCENA-VRd) [see Clinical Studies (14) ] . Among patients receiving SARCLISA ESCENA-VRd, 97% were exposed to SARCLISA ESCENA for 6 months or longer and 50% were exposed for 12 months or longer. Serious adverse reactions occurred in 45% of patients who received SARCLISA ESCENA-VRd. Serious adverse reactions >5% of patients included pneumonia (8%). Fatal adverse reactions occurred in 2.7% of patients who received SARCLISA ESCENA-VRd, including cardio-respiratory arrest (1.4%) and myocardial infarction (1.4%). Permanent treatment discontinuation due to an adverse reaction occurred in 4.1% of patients who received SARCLISA ESCENA-VRd. Adverse reactions which resulted in permanent discontinuation of SARCLISA ESCENA-VRd in 1 patient each included pyelonephritis, cardio-respiratory arrest, and myocardial infarction. The most common adverse reactions (≥20%) were peripheral neuropathy, constipation, diarrhea, fatigue, musculoskeletal pain, upper respiratory tract infections, injection site reaction, insomnia, edema, rash, and erythema. The most common hematology laboratory abnormalities (≥40%) were decreased lymphocytes, decreased leukocytes, decreased platelets, decreased neutrophils, and decreased hemoglobin. Table 7 summarizes the adverse reactions in IsaSoCut. Table 7: Adverse Reactions (≥10%) in Patients Who Received SARCLISA ESCENA-VRd in IsaSoCut SARCLISA ESCENA-VRd (N=74) Adverse Reaction All Grades (%) Grade 3 or 4 (%) Nervous system disorders Peripheral neuropathy Peripheral neuropathy included the grouping of paresthesias, dysesthesias, hypoesthesias, and peripheral neuropathies (sensory and motor). 59 5 Gastrointestinal disorders Constipation 43 2.7 Diarrhea 41 0 Nausea 15 0 Vomiting 11 0 Abdominal pain Abdominal pain refers to the grouping of gastrointestinal and abdominal pains (excluding oral and throat). 11 0 General disorders and administration site conditions Fatigue Fatigue is a grouping of asthenic conditions. 37 2.7 Injection site reaction 27 0 Edema Edema is a grouping of the following terms: eyelid edema, face edema, generalized edema, localized edema, edema, and edema peripheral. 20 1.4 Pyrexia 11 0 Infections and infestations Upper respiratory tract infections Upper respiratory tract infections is a grouping of viral and pathogen unspecified infections. 30 0 COVID-19 COVID-19 is a grouping of Coronavirus infections. 18 5 Pneumonia Pneumonia is a grouping of pneumonia from bacterial and viral origins. 15 8 Bronchitis 14 0 Influenza 12 0 Urinary tract infection Urinary tract infection is a grouping of genitourinary tract infections (bacterial origin or pathogen unspecified). 12 0 Psychiatric disorders Insomnia 26 0 Skin and subcutaneous tissue disorders Rash Rash is a grouping of the following terms: drug eruption, eczema, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, and rash pustular. 20 2.7 Erythema 20 0 Musculoskeletal and connective tissue disorders Musculoskeletal pain Musculoskeletal pain is a grouping of the following terms: arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, pain in extremity, and spinal pain. 32 2.7 Back pain 16 0 Muscle spasms 14 0 Vascular disorders Hypotension Hypotension is a grouping of the following terms: hypotension and orthostatic hypotension. 16 2.7 Investigations Weight decreased 14 0 Clinically relevant adverse reactions in <10% of patients who received SARCLISA ESCENA in combination with bortezomib, lenalidomide, and dexamethasone included systemic administration reactions. Table 8 summarizes the laboratory abnormalities in IsaSoCut. Table 8: Laboratory Abnormalities That Worsened (≥30%) From Baseline in Patients Who Received SARCLISA ESCENA-VRd in IsaSoCut Laboratory Abnormality SARCLISA ESCENA-VRd (N=74) All Grades (%) Grade 3 or 4 (%) The denominator used for the percentage calculation is the number of patients with at least 1 evaluation of the laboratory test during the considered observation period. Hematology Lymphocytes decreased 92 64 Leukocytes decreased 92 30 Platelets decreased 82 26 Neutrophils decreased 76 49 Hemoglobin decreased 41 8 Chemistry Alkaline phosphatase increased 42 0

8.1 Pregnancy Risk Summary Based on its mechanism of action [see Clinical Pharmacology (12.1) ] , SARCLISA ESCENA can cause fetal harm when administered to a pregnant woman. There are no available data on SARCLISA ESCENA use in pregnant women to evaluate for a drug-associated risk. The assessment of isatuximab-irfc-associated risks is based on its mechanism of action and data from target antigen CD38 knockout animal models (see Data ). No animal reproduction studies were conducted with isatuximab-irfc. Advise pregnant women of the potential risk to a fetus. 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 ESCENA 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 adverse reactions Immunoglobulin G1 monoclonal antibodies are known to cross the placenta. Based on its mechanism of action, SARCLISA ESCENA 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 ESCENA 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 embryonic development (frogs).