b'FASENRA (benralizumab) injection, for subcutaneous use 228-Week TrialLactation AdversereactionsfromTrial3with28weeksoftreatmentwithFASENRA(n=73)orplaceboRisk Summary(n=75)inwhichtheincidencewasmorecommoninFASENRAthanplaceboincludeThereisnoinformationregardingthepresenceofbenralizumabinhumanoranimalmilk,andheadache (8.2% compared to 5.3%, respectively) and pyrexia (2.7% compared to 1.3%,theeffectsofbenralizumabonthebreastfedinfantandonmilkproductionarenotknown.respectively) [see Clinical Studies (14) in the full Prescribing Information]. The frequenciesHowever,benralizumabisahumanizedmonoclonalantibody(IgG1/-class), and immuno-fortheremainingadversereactionswithFASENRAweresimilartoplacebo. globulinG(IgG)ispresentinhumanmilkinsmallamounts.Ifbenralizumabistransferred Injectionsitereactionsinto human milk, the effects of local exposure in the gastrointestinal tract and potential InTrials1and2,injectionsitereactions(e.g.,pain,erythema,pruritus,papule)occurred limitedsystemicexposureintheinfanttobenralizumabareunknown.Thedevelopmentalandat a rate of 2.2% in patients treated with FASENRA compared with 1.9% in patients treatedhealthbenefitsofbreastfeedingshouldbeconsideredalongwiththemothersclinicalneedwithplacebo. forbenralizumabandanypotentialadverseeffectsonthebreast-fedchildfrombenralizumabImmunogenicity or from the underlying maternal condition.As with all therapeutic proteins, there is potential for immunogenicity. The detection ofPediatric Use antibodyformationishighlydependentonthesensitivityandspecificityoftheassay.Therewere108adolescentsaged12to17withasthmaenrolledinthePhase3exacerbationAdditionally,theobservedincidenceofantibody(includingneutralizingantibody)positivitytrials(Trial1:n=53,Trial2:n=55).Ofthese,46receivedplacebo,40receivedFASENRAeveryinanassaymaybeinfluencedbyseveralfactorsincludingassaymethodology,sample4weeksfor3doses,followedbyevery8weeksthereafter,and22receivedFASENRAevery handling, timing of sample collection, concomitant medications, and underlying disease. For4weeks.Patientswererequiredtohaveahistoryof2ormoreasthmaexacerbations thesereasons,comparisonoftheincidenceofantibodiestobenralizumabinthestudies requiring oral or systemic corticosteroid treatment in the past 12 months and reduced lung describedbelowwiththeincidenceofantibodiesinotherstudiesortootherproductsmay functionatbaseline(pre-bronchodilatorFEV 1 90%) despite regular treatment with medium bemisleading. or high dose ICS and LABA with or without OCS or other controller therapy. The pharmaco- Overall,treatment-emergentanti-drugantibodyresponsedevelopedin13%ofpatientskineticsofbenralizumabinadolescents12to17yearsofagewereconsistentwithadultstreated with FASENRA at the recommended dosing regimen during the 48 to 56 weekbasedonpopulationpharmacokineticanalysisandthereductioninbloodeosinophilcountstreatmentperiod.Atotalof12%ofpatientstreatedwithFASENRAdevelopedneutralizingwassimilartothatobservedinadultsfollowingthesameFASENRAtreatment.Theadverseantibodies. Anti-benralizumab antibodies were associated with increased clearance ofeventprofileinadolescentswasgenerallysimilartotheoverallpopulationinthePhase3benralizumabandincreasedbloodeosinophillevelsinpatientswithhighanti-drugantibody studies [see Adverse Reactions (6.1) in the full Prescribing Information]. The safety and titerscomparedtoantibodynegativepatients.Noevidenceofanassociationofanti-drug efficacyinpatientsyoungerthan12yearsofagehasnotbeenestablished.antibodieswithefficacyorsafetywasobserved. Geriatric Use Thedatareflectthepercentageofpatientswhosetestresultswerepositiveforantibodiesto Ofthetotalnumberofpatientsinclinicaltrialsofbenralizumab,13%(n=320)were65andbenralizumabinspecificassays. over, while 0.4% (n=9) were 75 and over. No overall differences in safety or effectiveness Postmarketing Experience wereobservedbetweenthesepatientsandyoungerpatients,andotherreportedclinical In addition to adverse reactions reported from clinical trials, the following adverse reactionsexperiencehasnotidentifieddifferencesinresponsesbetweentheelderlyandyounger havebeenidentifiedduringpostapprovaluseofFASENRA.Becausethesereactionsare patients,butgreatersensitivityofsomeolderindividualscannotberuledout.reportedvoluntarilyfromapopulationofuncertainsize,itisnotalwayspossibletoreliably OVERDOSAGE estimatetheirfrequencyorestablishacausalrelationshiptodrugexposure.Theseevents Dosesupto200mgwereadministeredsubcutaneouslyinclinicaltrialstopatientswithhavebeenchosenforinclusionduetoeithertheirseriousness,frequencyofreporting,or eosinophilic disease without evidence of dose-related toxicities.causalconnectiontoFASENRAoracombinationofthesefactors. Thereisnospecifictreatmentforanoverdosewithbenralizumab.Ifoverdoseoccurs,theImmune System Disorders: Hypersensitivity reactions, including anaphylaxis. patientshouldbetreatedsupportivelywithappropriatemonitoringasnecessary.DRUG INTERACTIONS PATIENT COUNSELING INFORMATION Noformaldruginteractionstudieshavebeenconducted. Advisethepatientsand/orcaregiverstoreadtheFDA-approvedpatientlabeling(Patient USE IN SPECIFIC POPULATIONSInformationandInstructionsforUseforFASENRAPEN)beforethepatientstartsusingFASENRAandeachtimetheprescriptionisrenewedastheremaybenewinformationtheyPregnancyneed to know.PregnancyExposureRegistry Providepropertrainingtopatientsand/orcaregiversonpropersubcutaneousinjection There is a pregnancy exposure registry that monitors pregnancy outcomes in womentechniqueusingtheFASENRAPEN,includingaseptictechnique,andthepreparationandexposed to FASENRA during pregnancy. Healthcare providers can enroll patients or encourageadministrationofFASENRAPENpriortouse.Advisepatientstofollowsharpsdisposal patientstoenrollthemselvesbycalling1-877-311-8972orvisitingmothertobaby.org/Fasenra. recommendations[see Instructions for Use in the full Prescribing Information].Risk Summary Hypersensitivity ReactionsThe data on pregnancy exposure from the clinical trials are insufficient to inform on drug-Inform patients that hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, associatedrisk.Monoclonalantibodiessuchasbenralizumabaretransportedacrosstherash) have occurred after administration of FASENRA. These reactions generally occurred placentaduringthethirdtrimesterofpregnancy;therefore,potentialeffectsonafetusarewithinhoursofFASENRAadministration,butinsomeinstanceshadadelayedonset(i.e.,likelytobegreaterduringthethirdtrimesterofpregnancy.Inaprenatalandpostnataldays). Instruct patients to contact their healthcare provider if they experience symptoms of development study conducted in cynomolgus monkeys, there was no evidence of fetalan allergic reaction [see Warnings and Precautions (5.1) in the full Prescribing Information].harmwithIVadministrationofbenralizumabthroughoutpregnancyatdosesthatproducedNot for Acute Symptoms or Deteriorating Disease exposures up to approximately 310 times the exposure at the maximum recommendedInformpatientsthatFASENRAdoesnottreatacuteasthmasymptomsoracute humandose(MRHD)of30mgSC[seeData]. exacerbations.InformpatientstoseekmedicaladviceiftheirasthmaremainsuncontrolledIntheU.S.generalpopulation,theestimatedbackgroundriskofmajorbirthdefectsand or worsens after initiation of treatment with FASENRA [see Warnings and Precautions (5.2) miscarriageinclinicallyrecognizedpregnanciesis2%to4%and15%to20%,respectively. in the full Prescribing Information].Clinical ConsiderationsReduction of Corticosteroid Dosage Disease-associated maternal and/or embryo/fetal risk: Inform patients to not discontinue systemic or inhaled corticosteroids except under the In women with poorly or moderately controlled asthma, evidence demonstrates that there isdirect supervision of a physician. Inform patients that reduction in corticosteroid dose may anincreasedriskofpreeclampsiainthemotherandprematurity,lowbirthweight,andsmall beassociatedwithsystemicwithdrawalsymptomsand/orunmaskconditionspreviouslyforgestationalageintheneonate.Thelevelofasthmacontrolshouldbecloselymonitoredin suppressedbysystemiccorticosteroidtherapy[see Warnings and Precautions (5.3) in the pregnantwomenandtreatmentadjustedasnecessarytomaintainoptimalcontrol. full Prescribing Information].Data PregnancyExposureRegistry Animal DataInform women there is a pregnancy exposure registry that monitors pregnancy outcomes In a prenatal and postnatal development study, pregnant cynomolgus monkeys receivedinwomenexposedtoFASENRAduringpregnancyandthattheycanenrollinthePregnancy benralizumabfrombeginningonGD20toGD22(dependentonpregnancydetermination),ExposureRegistrybycalling1-877-311-8972orbyvisitingmothertobaby.org/Fasenra on GD35, once every 14 days thereafter throughout the gestation period and 1-month[see Use in Specific Populations (8.1) in the full Prescribing Information].postpartum (maximum 14 doses) at doses that produced exposures up to approximatelyManufacturedby310timesthatachievedwiththeMRHD(onanAUCbasiswithmaternalIVdosesuptoAstraZeneca AB30mg/kgonceevery2weeks).BenralizumabdidnotelicitadverseeffectsonfetalorSdertlje,SwedenSE-15185neonatalgrowth(includingimmunefunction)upto6.5monthsafterbirth.Therewasno USLicenseNo.2059evidenceoftreatment-relatedexternal,visceral,orskeletalmalformations.Benralizumabwas Distributedbynotteratogenicincynomolgusmonkeys.Benralizumabcrossedtheplacentaincynomolgus AstraZenecaPharmaceuticalsLP,monkeys.Benralizumabconcentrationswereapproximatelyequalinmothersandinfants Wilmington, DE 19850onpostpartumday7,butwerelowerininfantsatlatertimepoints.Eosinophilcountswere FASENRA is a trademark of the AstraZeneca group of companies.suppressedininfantmonkeyswithgradualrecoveryby6monthspostpartum;however, AstraZeneca 2019recoveryofeosinophilcountswasnotobservedforoneinfantmonkeyduringthisperiod.Rev.02/21US-510163/21US-68979_US-51016 Fasenra US Medicine.indd 3 12/5/22 1:53 PM'