b'B:8.5" B:8.5"T:7.5" T:7.5"S:7" S:7"Serious adverse reactions occurred in 59% of patients receiving Isa-Kd. The most frequent SARCLISASARCLISA seriousadversereactionsin 5%ofpatientswhoreceivedIsa-Kdwerepneumonia(25%)and (isatuximab-irfc) injection, for intravenous use (isatuximab-irfc) injection, for intravenous useupperrespiratorytractinfections(9%).Adversereactionswithafataloutcomeduringtreatment Table 6: Hematology Laboratory Abnormalities During the Treatment Period in classication based on International Myeloma Working Group (IMWG) criteria [see Warningswere reported in 3.4% of patients in the Isa-Kd group (those occurring in more than 1% of Patients Receiving Isa-Kd versus Kd in IKEMA and Precautions (5.4)].patients were pneumonia occurring in 1.7% and cardiac failure in 1.1% of patients). 8 USE IN SPECIFIC POPULATIONSPermanent treatment discontinuation due to an adverse reaction (grades 14) occurred in 8% Laboratory SARCLISA + Carlzomib + Carlzomib + 8.1 Pregnancyof patients who received Isa-Kd. The most frequent adverse reactions requiring permanent Parameter Dexamethasone (Isa-Kd) Dexamethasone (Kd)Risk Summarydiscontinuation in patients who received Isa-Kd were infections (2.8%). SARCLISAalone was (N=177) (N=122) SARCLISAcancausefetalharmwhenadministeredtoapregnantwoman.Theassessmentofdiscontinued in 0.6% of patients due to infusion-related reactions. isatuximab-irfc-associated risks is based on the mechanism of action and data from targetDosage interruptions due to an adverse reaction occurred in 33% of patients who received All Grade 3 Grade 4 All Grade 3 Grade 4Grades (%) (%) Grades (%) (%) antigen CD38 knockout animal models (see Data).There are no available data on SARCLISASARCLISA. The most frequent adverse reaction requiring dosage interruption was infusion- (%) (%) useinpregnantwomentoevaluateforadrug-associatedriskofmajorbirthdefects,miscarriagerelated reaction (30%). or adverse maternal or fetal outcomes. Animal reproduction toxicity studies have not beenThe most common adverse reactions (20%) were upper respiratory tract infection, infusion- Hemoglobin 99 22 0 99 20 0 conducted with isatuximab-irfc. The estimated background risk of major birth defects andrelated reactions, fatigue, hypertension, diarrhea, pneumonia, dyspnea, insomnia, bronchitis, decreased miscarriagefortheindicatedpopulationisunknown.Allpregnancieshaveabackgroundriskofcough, and back pain. Lymphocytes 94 52 17 95 43 14 birth defect, miscarriage, or other adverse outcomes. In the U.S. general population, theTable 5 summarizes the adverse reactions in IKEMA. decreased estimated background risk of major birth defects and miscarriage in clinically recognizedpregnancies is 2% to 4% and 15% to 20%, respectively.Table 5: Adverse Reactions (10%) in Patients Receiving SARCLISA, Carlzomib, Platelets decreased 94 19 11 88 16 8 The combination of SARCLISA and pomalidomide is contraindicated in pregnant womenand Dexamethasone with a Difference Between Arms of 5% Compared to Control Neutrophils 55 18 1.7 43 7 0.8 because pomalidomide may cause birth defects and death of the unborn child. Refer to theArm in IKEMA decreased pomalidomideprescribinginformationonuseduringpregnancy.PomalidomideisonlyavailableAdverse SARCLISA + Carlzomib + Carlzomib + Dexamethasone through a REMS program.Reactions Dexamethasone (Isa-Kd) (Kd) The denominator used to calculate the percentage was based on the safety population. Clinical Considerations(N=177) (N=122) Description of Selected Adverse Reactions Fetal/neonatal reactionsInfusion-related reactions Immunoglobulin G1 monoclonal antibodies are known to cross the placenta. Based on itsAll Grade Grade All Grade Grade In ICARIA-MM, infusion-related reactions (dened as adverse reactions associated with the mechanismofaction,SARCLISAmaycausedepletionoffetalCD38-positiveimmunecellsandGrades 3 4 Grades 3 4 SARCLISAinfusions,withanonsettypicallywithin24hoursfromthestartoftheinfusion)were decreasedbonedensity.Deferadministrationoflivevaccinestoneonatesandinfantsexposed(%) (%) (%) (%) (%) (%) reported in 58 patients (38%) treated with SARCLISA.All patients who experienced infusion- to SARCLISA in utero until a hematology evaluation is completed.General disorders and administration site conditions related reactions experienced them during the 1st infusion of SARCLISA, with 3 patients (2%) Dataalso having infusion-related reactions at their 2nd infusion, and 2 patients (1.3%) at their 4th Animal dataInfusion-related 46 0.6 0 3.3 0 0 infusion.Grade1infusion-relatedreactionswerereportedin3.9%,grade2in32%,grade3inreaction * 1.3%,andgrade4in1.3%ofthepatients.Signsandsymptomsofgrade3or4infusion-related MicethatweregeneticallymodiedtoeliminateallCD38expression(CD38knockoutmice)had reactions included dyspnea, hypertension, and bronchospasm. The incidence of infusion reduced bone density which recovered 5 months after birth. Data from studies using CD38Fatigue 42 5 0 32 3.3 0 interruptions because of infusion-related reactions was 30%. The median time to infusion knockout animal models also suggest the involvement of CD38 in regulating humoral immuneInfections interruption was 55 minutes. SARCLISA was discontinued in 2.6% of patients due to responses (mice), feto-maternal immune tolerance (mice), and early embryonic developmentinfusion-related reactions. (frogs).Upper respiratory 67 9 0 57 7 0 In IKEMA, infusion-related reactions were reported in 81 patients (46%) treated with Isa-Kd. 8.2 Lactationtract infectionGrade1infusion-relatedreactionswerereportedin14%,grade2in32%,andgrade3in0.6% Risk SummaryPneumonia36 19 3.4 30 15 2.5 of the patients treated with Isa-Kd. Signs and symptoms of grade 3 infusion-related reactions Therearenoavailabledataonthepresenceofisatuximab-irfcinhumanmilk,milkproduction,included dyspnea and hypertension. SARCLISA was discontinued in 0.6% of patients due to or S:10" the effects T:10.5" B:11.25" on the breastfed child. Maternal immunoglobulin G is known to be present in S:10" T:10.5" B:11.25"Bronchitis24 2.3 0 13 0.8 0 infusion-related reactions [see Warnings and Precautions (5.1)]. humanmilk.TheeffectsoflocalgastrointestinalexposureandlimitedsystemicexposureintheInaseparatestudy(TCD14079PartB)withSARCLISA10mg/kgadministeredfroma250mL breastfed infant to SARCLISA are unknown. Because of the potential for serious adverseVascular disorders xed-volume infusion in combination with Pd, infusion-related reactions (all grade 2) were reactionsinthebreastfedchildfromisatuximab-irfcadministeredincombinationwithpomalido-Hypertension # 37 20 0.6 32 18 1.6 reported in 40% of patients, at the rst administration, the day of the infusion. Overall, the mide and dexamethasone, advise lactating women not to breastfeed during treatment withinfusion-related reactions of SARCLISA 10 mg/kg administered as a 250 mL xed-volumeRespiratory, thoracic and mediastinal disorders infusion were similar to that of SARCLISA as administered in ICARIA-MM. SARCLISA. Refer to pomalidomide prescribing information for additional information.Infections 8.3 Females and Males of Reproductive PotentialDyspnea29 5 0 24 0.8 0 In ICARIA-MM, the incidence of grade 3 or higher infections was 43% in the Isa-Pd group. SARCLISAcancausefetalharmwhenadministeredtoapregnantwoman[seeUseinSpecicCough23 0 0 15 0 0 Pneumonia was the most common severe infection with grade 3 reported in 22% of patients Populations (8.1)].in the Isa-Pd group compared to 16% in the Pd group, and grade 4 in 3.3% of patients in the Pregnancy TestingGastrointestinal disorders Isa-Pd group compared to 2.7% in the Pd group. Discontinuations from treatment due to With the combination of SARCLISAwith pomalidomide, refer to the pomalidomide labeling forinfectionwerereportedin2.6%ofpatientsintheIsa-Pdgroupcomparedto5%inthePdgroup. pregnancytestingrequirementspriortoinitiatingtreatmentinfemalesofreproductivepotential.Diarrhea 36 2.8 0 29 2.5 0 Fatal infections occurred in 3.3% of patients in the Isa-Pd group and in 4% in the Pd group.InIKEMA,theincidenceofgrade3orhigherinfectionswas38%intheIsa-Kdgroup.Pneumonia ContraceptionVomiting 15 1.1 0 9 0.8 0 was the most common severe infection with grade 3 in 19% of patients in the Isa-Kd group Females*Infusion-related reaction includes infusion-related reaction, cytokine release syndrome, and comparedto15%intheKdgroup,andgrade4in3.4%ofpatientsintheIsa-Kdgroupcompared Advisefemalepatientsofreproductivepotentialtouseeffectivecontraceptionduringtreatmenthypersensitivity. to2.5%intheKdgroup.Treatmentwasdiscontinuedduetoinfectionin2.8%ofpatientsinthe and for 5 months after the last dose of SARCLISA. Additionally, refer to the pomalidomideFatigue includes fatigue and asthenia. Isa-Kd group compared to 4.9% in the Kd group. Fatal infections occurred in 2.3% of patients labeling for contraception requirements prior to initiating treatment in females of reproductivein the Isa-Kd group and 0.8% in the Kd group. potential.Upper respiratory tract infection includes acute sinusitis, chronic sinusitis, H1N1 inuenza, Inrelapsedandrefractorymultiplemyelomaclinicaltrials,herpeszosterwasreportedin2%of MalesH3N2inuenza,inuenza,laryngitis,laryngitisviral,nasalherpes,nasopharyngitis,pharyngitis, patients.InICARIA-MM,theincidenceofherpeszosterwas4.6%intheIsa-Pdgroupcompared Refer to the pomalidomide prescribing information.pharyngotonsillitis, respiratory syncytial virus infection, rhinitis, sinusitis, sinusitis bacterial, to0.7%inthePdgroup,and,inIKEMA,incidencewas2.3%intheIsa-Kdgroupcomparedto 8.4 Pediatric Usetonsillitis, tracheitis, upper respiratory tract infection, viral rhinitis, respiratory tract infection, 1.6% in the Kd group. Safety and effectiveness of SARCLISA in pediatric patients have not been established.respiratorytractinfectionviral,inuenzalikeillness,parainuenzaevirusinfection,respiratory Cardiac failure 8.5 Geriatric Usetract infection bacterial, and viral upper respiratory tract infection. In IKEMA, cardiac failure (including cardiac failure, cardiac failure congestive, cardiac failure Of the total number of subjects in clinical studies of SARCLISA, 56% (586 patients) were 65Pneumonia includes atypical pneumonia, lower respiratory tract infection, lower respiratory acute,cardiacfailurechronic,leftventricularfailure,andpulmonaryedema)wasreportedin7% and over, while 16% (163 patients) were 75 and over. No overall differences in safety ortract infection viral, pneumocystis jirovecii pneumonia, pneumonia, pneumonia inuenzal, ofpatientswiththeIsa-Kdgroup(grade 3in4%)andin7%ofpatientswiththeKdgroup(grade effectiveness were observed between subjects 65 and over and younger subjects, and otherpneumonialegionella,pneumoniapneumococcal,pneumoniarespiratorysyncytialviral,pneu- 3 in 4.1%). Serious cardiac failure was observed in 4% of patients in the Isa-Kd group and reported clinical experience has not identied differences in responses between the adults 65monia streptococcal, pneumonia viral, pulmonary sepsis, and pulmonary tuberculosis. in 3.3% of patients in the Kd group. See the current prescribing information for carlzomib for years and over and younger patients, but greater sensitivity of some older individuals cannotBronchitis includes bronchitis, bronchitis viral, respiratory syncytial virus bronchitis, bronchitis more information. be ruled out.chronic, and tracheobronchitis. 7 DRUG INTERACTIONS7.1 Laboratory Test Interference#Hypertension includes hypertension, blood pressure increased, and hypertensive crisis. Interference with Serological Testing Manufactured by:Dyspnea includes dyspnea and dyspnea exertional. SARCLISA, an anti-CD38 antibody, may interfere with blood bank serologic tests with false sano-aventis U.S. LLCCough includes cough, productive cough, and allergic cough. positive reactions in indirect antiglobulin tests (indirect Coombs tests), antibody detection Bridgewater, NJ 08807(screening) tests, antibody identication panels, and antihuman globulin crossmatches in A SANOFI COMPANYpatientstreatedwithSARCLISA[seeWarningsandPrecautions(5.4)].Inpatientswithpersistent U.S. License No. 1752Table 6 summarizes the hematology laboratory abnormalities in IKEMA. very good partial response, where interference is suspected, consider using an FDA-clearedisatuximab-irfc-specicIFEassaytodistinguishisatuximabfromanyremainingendogenousM SARCLISA is a registered trademark of Sanoprotein in the patients serum to facilitate determination of a complete response.Interference with Serum Protein Electrophoresis and Immunoxation Tests 2022 sano-aventis U.S. LLCSARCLISAmay be incidentally detected by serum protein electrophoresis and immunoxationassays used for the monitoring of M-protein and may interfere with accurate response ISA-BPLR-SL-NOV23 Revised: November 202312049085_SAR_US_Branded_2_Page_Journal Ad_A_M4FR.indd 4 1/5/24 4:14 PM 12049085_SAR_US_Branded_2_Page_Journal Ad_A_M4FR.indd 5 1/5/24 4:14 PMPREPARED BYPREPARED BY 12049085-vc12049124 US Branded 2-Page Journal Ad (A-size) Label Update M4FR 12049085-vc12049124 US Branded 2-Page Journal Ad (A-size) Label Update M4FRJob info Images FontsSpecial Instructions Job info Images FontsSpecial InstructionsDate: 1-5-2024 4:14 PM isa-bplr-sl-nov23.pdf (100%; 52KB) Arial Narrow (Regular) Rename f12049085 Sarclisa US Branded 2-PageDate: 1-5-2024 4:14 PM isa-bplr-sl-nov23.pdf (100%; 52KB) Arial Narrow (Regular) Rename f12049085 Sarclisa US Branded 2-Page Client: NOVARTIS Journal Ad Label Update - MAT-US-2307253-v2.0 Client: NOVARTIS Journal Ad Label Update - MAT-US-2307253-v2.0Product: US Sarclisa Product: US SarclisaClient Code: MAT-US-2307253-v2.0-12/2023 Additional Information Client Code: MAT-US-2307253-v2.0-12/2023 Additional InformationWF Issue # 10351122 At Release, rename to: "12049085 Sarclisa USWF Issue # 10351122 At Release, rename to: "12049085 Sarclisa US Releasing as: PDFx1A Branded 2-Page Journal Ad Label Update - MAT- Releasing as: PDFx1A Branded 2-Page Journal Ad Label Update - MAT-Final Size: 7.5" x 10.5" US-2307253-v2.0" Final Size: 7.5" x 10.5" US-2307253-v2.0"Finishing: Trim Finishing: TrimGutter: -Inks Additional Comments for Sizing Gutter: -Inks Additional Comments for SizingColors: 4C & BWBlack None Colors: 4C & BWBlack NoneTeam TeamProducer: Anna Volkova Producer: Anna VolkovaAD: Melissa Petty AD: Melissa PettyAE: Ian Grabowich Scale: 1"= 1" AE: Ian Grabowich Scale: 1"= 1"QC: LW Bleed 17" w x 11.25" h 17" w x 11.25" h QC: LW Bleed 17" w x 11.25" h 17" w x 11.25" hProduction: Heather Cave Trim/Flat 15" w x 10.5" h 15" w x 10.5" h Production: Heather Cave Trim/Flat 15" w x 10.5" h 15" w x 10.5" hDigital Artist: M. Tenga Live/Safety 14.5" w x 10" h 14.5" w x 10" hDigital Artist: M. Tenga Live/Safety 14.5" w x 10" h 14.5" w x 10" h Path: PrePress:Sanofi:Sanofi_Sarclisa_US_H:12049085:12049085_SAR_US_Branded_2_Page_Journal Ad_A_M4FR.indd Path: PrePress:Sanofi:Sanofi_Sarclisa_US_H:12049085:12049085_SAR_US_Branded_2_Page_Journal Ad_A_M4FR.inddPDFX1A _ PDFX1A _'