BALVERSA

1 INDICATIONS AND USAGE BALVERSA is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC) with susceptible FGFR3 genetic alterations whose disease has progressed on or after at least one line of prior systemic therapy. Select patients for therapy based on an FDA-approved companion diagnostic for BALVERSA [see Dosage and Administration (2.1) and Clinical Studies (14.1) ] . BALVERSA is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (mUC) with susceptible FGFR3 genetic alterations whose disease has progressed on or after at least one line of prior systemic therapy. Select patients for therapy based on an FDA-approved companion diagnostic for BALVERSA. ( 1 , 2.1 ) Limitations of Use BALVERSA is not recommended for the treatment of patients who are eligible for and have not received prior PD-1 or PD-L1 inhibitor therapy. ( 1 , 14.1 ) Limitations of Use BALVERSA is not recommended for the treatment of patients who are eligible for and have not received prior PD-1 or PD-L1 inhibitor therapy [see Clinical Studies (14.1) ] .

6 ADVERSE REACTIONS The following serious adverse reactions are also described elsewhere in the labeling: Ocular Disorders [see Warnings and Precautions (5.1) ] . Hyperphosphatemia [see Warnings and Precautions (5.2) ] . The most common (>20%) adverse reactions, including laboratory abnormalities, were increased phosphate, nail disorders, stomatitis, diarrhea, increased creatinine, increased alkaline phosphatase, increased alanine aminotransferase, decreased hemoglobin, decreased sodium, increased aspartate aminotransferase, fatigue, dry mouth, dry skin, decreased phosphate, decreased appetite, dysgeusia, constipation, increased calcium, dry eye, palmar-plantar erythrodysesthesia syndrome, increased potassium, alopecia, and central serous retinopathy. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Products, LP. at 1-800-526-7736 (1-800-JANSSEN and www.BALVERSA.com) 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. The pooled safety population described in the WARNINGS AND PRECAUTIONS reflects exposure to BALVERSA as a single agent at the recommended dose (8 to 9 mg orally daily) in 479 patients with advanced urothelial cancer and FGFR alterations in 42756493BLC3001 (NCT03390504), 42756493BLC2001 (NCT02365597), 42756493BLC2002 (NCT 03473743), and 42756493EDI1001 (NCT01703481). Among 479 patients who received BALVERSA, the median duration of treatment was 4.8 months (range: 0.1 to 43 months). In this pooled safety population, the most common (>20%) adverse reactions, including laboratory abnormalities, were increased phosphate, nail disorders, stomatitis, diarrhea, increased creatinine, increased alkaline phosphatase, increased alanine aminotransferase, decreased hemoglobin, decreased sodium, increased aspartate aminotransferase, fatigue, dry mouth, dry skin, decreased phosphate, decreased appetite, dysgeusia, constipation, increased calcium, dry eye, palmar-plantar erythrodysesthesia syndrome, increased potassium, alopecia, and central serous retinopathy. BLC3001 The safety of BALVERSA was evaluated in Cohort 1 of the BLC3001 study that included patients with locally advanced unresectable or metastatic urothelial carcinoma which had susceptible FGFR3 genetic alterations and were previously treated with a PD-1 or PD-L1 inhibitor [see Clinical Studies (14.1) ] . Patients received either BALVERSA (8 mg orally once daily with individualized up-titration to 9 mg) (n=135) or chemotherapy (docetaxel 75 mg/m 2 once every 3 weeks or vinflunine 320 mg/m 2 once every 3 weeks) (n=112). Among patients who received BALVERSA, median duration of treatment was 4.8 months (range: 0.2 to 38 months). Serious adverse reactions occurred in 41% of patients who received BALVERSA. Serious reactions in >2% of patients included urinary tract infection (4.4%), hematuria (3.7%), hyponatremia (2.2%), and acute kidney injury (2.2%). Fatal adverse reactions occurred in 4.4% of patients who received BALVERSA, including sudden death (1.5%), pneumonia (1.5%), renal failure (0.7%), and cardiorespiratory arrest (0.7%). Permanent discontinuation of BALVERSA due to an adverse reaction occurred in 14% of patients. Adverse reactions which resulted in permanent discontinuation of BALVERSA in >2% of patients included nail disorders (3%) and eye disorders (2.2%). Dosage interruptions of BALVERSA due to an adverse reaction occurred in 72% of patients. Adverse reactions which required dosage interruption in >4% of patients included nail disorders (22%), stomatitis (19%), eye disorders (16%), palmar-plantar erythrodysesthesia syndrome (15%), diarrhea (10%), hyperphosphatemia (7%), increased aspartate aminotransferase (6%), and increased alanine aminotransferase (5%). Dose reductions of BALVERSA due to an adverse reaction occurred in 69% of patients. Adverse reactions which required dose reductions in >4% of patients included nail disorders (27%), stomatitis (19%), eye disorders (17%), palmar-plantar erythrodysesthesia syndrome (12%), diarrhea (7%), dry mouth (4.4%), and hyperphosphatemia (4.4%). Table 3 presents adverse reactions reported in ≥15% of patients treated with BALVERSA at 8 or 9 mg once daily versus chemotherapy. Table 3: Adverse Reactions Reported in ≥15% of Patients Who Received BALVERSA Versus Chemotherapy (Study BLC3001) Adverse Reaction BALVERSA (N=135) Chemotherapy (N=112) All Grades (%) Grade 3–4 (%) All Grades (%) Grade 3–4 (%) Skin and subcutaneous tissue disorders Nail disorders Includes multiple terms 70 12 5 0 Palmar-plantar erythrodysesthesia syndrome 30 10 0.9 0 Dry skin 27 1.5 6 0 Alopecia 25 0.7 24 0 Gastrointestinal disorders Diarrhea 63 3 17 2.7 Stomatitis 56 10 18 1.8 Dry Mouth 39 0 3.6 0 Constipation 27 0 28 1.8 Nervous system disorders Dysgeusia 30 0.7 7 0 General disorders Fatigue 29 1.5 42 7 Metabolism and nutrition disorders Decreased appetite 27 3 21 2.7 Eye disorders Dry eye 25 0.7 3.6 0 Central serous retinopathy 18 2.2 0 0 Investigations Decreased weight 22 2 2.7 0 Clinically relevant adverse reactions in <15% of patients who received BALVERSA included nausea (15%), pyrexia (15%), epistaxis (13%), vomiting (10%), and arthralgia (10%). Table 4 presents laboratory abnormalities reported in ≥15% of patients treated with BALVERSA at 8 or 9 mg once daily versus chemotherapy. Table 4: Selected Laboratory Abnormalities Reported in ≥15% of Patients Who Received BALVERSA Versus Chemotherapy; Cohort 1 Safety Analysis Set (Study BLC3001) Laboratory Abnormality BALVERSA (N=135 The denominator used to calculate the rate varied from 52 to 131 based on the number of patients with a baseline value and at least one post-treatment value. ) Chemotherapy (N=112 The denominator used to calculate the rate varied from 11 to 102 based on the number of patients with a baseline value and at least one post-treatment value. ) All Grades Severity graded per NCI CTCAE v4.03. (%) Grade 3–4 (%) All Grades (%) Grade 3–4 (%) Chemistry Increased phosphate 76 5 0 0 Increased alkaline phosphatase 54 4.7 29 1 Increased alanine aminotransferase 46 3.8 15 1 Increased aspartate aminotransferase 44 3.1 13 0 Decreased sodium 44 16 25 6 Increased creatinine 43 1.5 17 0 Decreased phosphate 34 8 25 3.6 Increased calcium 27 8 9 0 Increased potassium 24 0 21 0 Hematology Decreased hemoglobin 50 12 57 12 Decreased platelet count 17 1.5 18 1 Decreased neutrophil count 16 0.8 40 26 BLC2001 The safety of BALVERSA was evaluated in the BLC2001 study that included 87 patients with locally advanced or metastatic urothelial carcinoma which had susceptible FGFR3 and other FGFR alterations, and which progressed during or following at least one line of prior chemotherapy including within 12 months of neoadjuvant or adjuvant chemotherapy [see Clinical Studies (14.1) ] . Patients were treated with BALVERSA at 8 mg orally once daily; with a dose increase to 9 mg in patients with phosphate levels <5.5 mg/dL on Day 14 of Cycle 1. Median duration of treatment was 5.3 months (range: 0 to 17 months). Serious adverse reactions occurred in 41% of patients. The most frequent (>3%) serious adverse reactions were central serous retinopathy (4.6%), urinary tract infection (3.4%), and general physical health deterioration (3.4%). Fatal adverse reactions occurred in 8% of patients, including acute myocardial infarction (1.1%). Permanent discontinuation of BALVERSA due to an adverse reaction occurred in 21% of patients. The most frequent (≥ 2%) reasons for permanent discontinuation included central serous retinopathy (4.6%), general physical health deterioration (3.4%), palmar-plantar erythrodysesthesia syndrome (2.3%), acute kidney injury (2.3%), and fatigue (2.3%). Dosage interruptions of BALVERSA occurred in 68% of patients. The most frequent (≥ 5%) adverse reactions requiring dosage interruption included hyperphosphatemia (24%), stomatitis (17%), nail disorders (16%), central serous retinopathy (9%), palmar-plantar erythro-dysesthesia syndrome (8%), and fatigue (8%). Dose reductions of BALVERSA occurred in 53% of patients. The most frequent (≥ 5%) adverse reactions for dose reductions included nail disorders (21%), stomatitis (15%), central serous retinopathy (14%), hyperphosphatemia (7%), palmar-plantar erythro-dysesthesia syndrome (7%), fatigue (6%), and blurred vision (6%). Table 5 presents adverse reactions reported in ≥15% of patients treated with BALVERSA at 8 mg or 9 mg once daily. Table 5: Adverse Reactions Reported in ≥15% of Patients (Study BLC2001) Adverse Reaction BALVERSA 8 mg daily (N=87) All Grades (%) Grade 3–4 (%) Gastrointestinal disorders Stomatitis Includes multiple terms 62 11 Diarrhea 48 4.6 Dry mouth 45 0 Constipation 28 1.1 Nausea 21 1.1 Skin and subcutaneous tissue disorders Nail disorders 62 14 Dry skin 37 0 Alopecia 26 0 Palmar-plantar erythrodysesthesia syndrome 26 6 General disorders and admin. site conditions Fatigue , Includes fatal adverse reactions (n=2) 54 8 Decreased weight 16 0 Metabolism and nutrition disorders Decreased appetite 38 0.0 Nervous system disorders Dysgeusia 38 1.1 Eye disorders Dry eye 29 1.1 Central serous retinopathy 28 4.6 Blurred vision 17 0 Infections and Infestations Urinary tract infection 17 6 Clinically relevant adverse reactions in <15% of patients who received BALVERSA included pyrexia (14%), extremity pain (13%), vomiting (13%), and peripheral edema (10%). Table 6 presents laboratory abnormalities reported in ≥15% of patients treated with BALVERSA at 8 mg or 9 mg once daily. Table 6: Selected Laboratory Abnormalities Reported in ≥ 15% of Patients Laboratory Abnormality BALVERSA 8 mg daily (N=87 The denominator used to calculate the rate varied from 83 to 86 based on the number of patients with a baseline value and at least one post-treatment value. ) All Grades (%) Grade 3–4 (%) Chemistry Increased phosphate 76 1.2 Increased creatinine 52 4.7 Increased alanine aminotransferase 41 1.2 Increased alkaline phosphatase 41 1.2 Decreased sodium 40 16 Decreased magnesium 31 1.2 Increased aspartate aminotransferase 30 0 Decreased phosphate 24 9 Increased calcium 22 3.5 Hematology Decreased hemoglobin 35 3.5 Decreased platelets 19 1.2 Decreased leukocytes 17 0

4 CONTRAINDICATIONS None. None. ( 4 )

11 DESCRIPTION Erdafitinib, the active ingredient in BALVERSA, is a kinase inhibitor. The chemical name is N-(3,5-dimethoxyphenyl)-N'-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2-diamine. Erdafitinib is a yellow powder. It is practically insoluble, or insoluble to freely soluble in organic solvents, and slightly soluble to practically insoluble, or insoluble in aqueous media over a wide range of pH values. The molecular formula is C 25 H 30 N 6 O 2 and molecular weight is 446.56. Chemical structure of erdafitinib is as follows: BALVERSA ® (erdafitinib) tablets are supplied as 3 mg, 4 mg or 5 mg film-coated tablets for oral administration and contains the following inactive ingredients: Tablet Core: Croscarmellose sodium, Magnesium stearate (from vegetable source), Mannitol, Meglumine, and Microcrystalline Cellulose. Film Coating: (Opadry amb II): Glycerol monocaprylocaprate Type I, Polyvinyl alcohol-partially hydrolyzed, Sodium lauryl sulfate, Talc, Titanium dioxide, Iron oxide yellow, Iron oxide red (for the orange and brown tablets only), Ferrosoferric oxide/iron oxide black (for the brown tablets only). Chemical Structure

2 DOSAGE AND ADMINISTRATION Confirm the presence of FGFR3 genetic alterations in tumor specimens prior to initiation of treatment with BALVERSA. ( 2.1 ) Recommended initial dosage: 8 mg orally once daily with a dose increase to 9 mg daily if criteria are met. ( 2.2 ) Swallow whole with or without food. ( 2.2 ) 2.1 Patient Selection Select patients for the treatment of locally advanced or metastatic urothelial carcinoma with BALVERSA based on the presence of susceptible FGFR3 genetic alterations in tumor specimens as detected by an FDA-approved companion diagnostic [see Clinical Studies (14.1) ] . Information on FDA-approved tests for the detection of FGFR3 genetic alterations in urothelial cancer is available at: http://www.fda.gov/CompanionDiagnostics. 2.2 Recommended Dosage and Schedule The recommended starting dose of BALVERSA is 8 mg (two 4 mg tablets) orally once daily, with a dose increase to 9 mg (three 3 mg tablets) once daily based on tolerability, including hyperphosphatemia, at 14 to 21 days [see Dosage and Administration (2.3) ]. Swallow tablets whole with or without food. If vomiting occurs any time after taking BALVERSA, the next dose should be taken the next day. Treatment should continue until disease progression or unacceptable toxicity occurs. If a dose of BALVERSA is missed, it can be taken as soon as possible on the same day. Resume the regular daily dose schedule for BALVERSA the next day. Extra tablets should not be taken to make up for the missed dose. Dose Increase based on Serum Phosphate Levels Assess serum phosphate levels 14 to 21 days after initiating treatment. Increase the dose of BALVERSA to 9 mg once daily if serum phosphate level is < 9.0 mg/dL and there are no ocular disorders or Grade 2 or greater adverse reactions. If the phosphate level is 9.0 mg/dL or higher follow the relevant dose modifications in Table 2. Monitor phosphate levels monthly for hyperphosphatemia [see Pharmacodynamics (12.2) ] . 2.3 Dose Modifications for Adverse Reactions The recommended dose modifications for adverse reactions are listed in Table 1. Table 1: BALVERSA Dose Reduction Schedule Dose 1 st dose reduction 2 nd dose reduction 3 rd dose reduction 4 th dose reduction 5 th dose reduction 9 mg ➞ (three 3 mg tablets) 8 mg (two 4 mg tablets) 6 mg (two 3 mg tablets) 5 mg (one 5 mg tablet) 4 mg (one 4 mg tablet) Stop 8 mg ➞ (two 4 mg tablets) 6 mg (two 3 mg tablets) 5 mg (one 5 mg tablet) 4 mg (one 4 mg tablet) Stop Table 2 summarizes recommendations for dose interruption, reduction, or discontinuation of BALVERSA in the management of specific adverse reactions. Table 2: Dose Modifications for Adverse Reactions Adverse Reaction BALVERSA Dose Modification Hyperphosphatemia In all patients, restrict phosphate intake to 600–800 mg daily. <6.99 mg/dL Continue BALVERSA at current dose. 7–8.99 mg/dL Continue BALVERSA at current dose. Start phosphate binder with food until phosphate level is <7 mg/dL. Reduce the dose if serum phosphate remains ≥7 mg/dL for a period of 2 months or if clinically necessary. 9–10 mg/dL Withhold BALVERSA with weekly reassessments until level returns to <7 mg/dL. Then restart BALVERSA at the same dose level. Start phosphate binder with food until serum phosphate level returns to <7 mg/dL. Reduce the dose if serum phosphate remains ≥9 mg/dL for a period of 1 month or if clinically necessary. >10 mg/dL Withhold BALVERSA with weekly reassessments until level returns to <7 mg/dL. Then may restart BALVERSA at the first reduced dose level. If hyperphosphatemia (≥10 mg/dL) for >2 weeks, discontinue BALVERSA permanently. Medical management of symptoms as clinically relevant. Serum phosphate with life-threatening consequences; urgent intervention indicated (e.g., dialysis) Discontinue BALVERSA permanently. Central Serous Retinopathy (CSR) Any Withhold BALVERSA and perform an ophthalmic evaluation within 2 weeks: If improving within 14 days, restart BALVERSA at the current dose. If not improving within 14 days, withhold BALVERSA until improving; once improving, may resume at the next lower dose level. Upon restarting BALVERSA, monitor for recurrence every 1 to 2 weeks for a month. If recurs or has not improved after 4 weeks of withholding BALVERSA, consider permanent discontinuation. Other Adverse Reactions Dose adjustment graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAEv5.0). Grade 3 Withhold BALVERSA until resolves to Grade 1 or baseline, then may resume dose level lower. Grade 4 Permanently discontinue.

7 DRUG INTERACTIONS Moderate CYP2C9 or strong CYP3A4 inhibitors: Consider alternative agents or monitor closely for adverse reactions. ( 7.1 ) Strong CYP3A4 inducers: Avoid concomitant use with BALVERSA. ( 7.1 ) Moderate CYP3A4 inducers: Administer BALVERSA at a dose of 9 mg. ( 7.1 ) Serum phosphate level-altering agents: Avoid concomitant use with agents that can alter serum phosphate levels before the initial dose modification period. ( 2.3 , 7.1 ) P-gp substrates: Separate BALVERSA administration by at least 6 hours before or after administration of P-gp substrates with narrow therapeutic indices. ( 7.2 ) 7.1 Effect of Other Drugs on BALVERSA Table 7 summarizes drug interactions that affect the exposure of BALVERSA or serum phosphate level and their clinical management. Table 7: Drug Interactions that Affect BALVERSA Moderate CYP2C9 or Strong CYP3A4 Inhibitors Clinical Impact Co-administration of BALVERSA with moderate CYP2C9 or strong CYP3A4 inhibitors increased erdafitinib plasma concentrations [see Clinical Pharmacology (12.3) ]. Increased erdafitinib plasma concentrations may lead to increased drug-related toxicity [see Warnings and Precautions (5) ]. Clinical Management Consider alternative therapies that are not moderate CYP2C9 or strong CYP3A4 inhibitors during treatment with BALVERSA. If co-administration of a moderate CYP2C9 or strong CYP3A4 inhibitor is unavoidable, monitor closely for adverse reactions and consider dose modifications accordingly [see Dosage and Administration (2.3) ]. If the moderate CYP2C9 or strong CYP3A4 inhibitor is discontinued, resume the BALVERSA dose before dose modifications in the absence of drug-related toxicity. Strong CYP3A4 Inducers Clinical Impact Co-administration of BALVERSA with strong CYP3A4 inducers decreased erdafitinib plasma concentrations [see Clinical Pharmacology (12.3) ]. Decreased erdafitinib plasma concentrations may lead to decreased activity. Clinical Management Avoid co-administration of strong CYP3A4 inducers with BALVERSA. Moderate CYP3A4 Inducers Clinical Impact Co-administration of BALVERSA with moderate CYP3A4 inducers may decrease erdafitinib plasma concentrations [see Clinical Pharmacology (12.3) ]. Decreased erdafitinib plasma concentrations may lead to decreased activity. Clinical Management If a moderate CYP3A4 inducer must be co-administered at the start of BALVERSA treatment, administer BALVERSA at a dose of 9 mg daily. When a moderate CYP3A4 inducer is discontinued, continue BALVERSA at the same dose, in the absence of drug-related toxicity. Serum Phosphate Level-Altering Agents Clinical Impact Co-administration of BALVERSA with other serum phosphate level-altering agents may increase or decrease serum phosphate levels [see Pharmacodynamics (12.2) ]. Changes in serum phosphate levels due to serum phosphate level-altering agents (other than erdafitinib) may interfere with serum phosphate levels needed for the determination of initial dose increased based on serum phosphate levels [see Dosage and Administration (2.3) ]. Clinical Management Avoid co-administration of serum phosphate level-altering agents with BALVERSA before initial dose increase period based on serum phosphate levels (Days 14 to 21) [see Dosage and Administration (2.3) ]. 7.2 Effect of BALVERSA on Other Drugs Table 8 summarizes the effect of BALVERSA on other drugs and their clinical management. Table 8: BALVERSA Drug Interactions that Affect Other Drugs P-glycoprotein (P-gp) Substrates Clinical Impact Co-administration of BALVERSA with P-gp substrates may increase the plasma concentrations of P-gp substrates [see Clinical Pharmacology (12.3) ]. Increased plasma concentrations of P-gp substrates may lead to increased toxicity of the P-gp substrates. Clinical Management If co-administration of BALVERSA with P-gp substrates is unavoidable, separate BALVERSA administration by at least 6 hours before or after administration of P-gp substrates with narrow therapeutic index.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Erdafitinib is a kinase inhibitor that binds to and inhibits enzymatic activity of FGFR1, FGFR2, FGFR3 and FGFR4 based on in vitro data. Erdafitinib inhibited FGFR phosphorylation and signaling and decreased cell viability in cell lines expressing FGFR genetic alterations, including point mutations, amplifications, and fusions. Erdafitinib demonstrated antitumor activity in FGFR-expressing cell lines and xenograft models derived from tumor types, including bladder cancer. 12.2 Pharmacodynamics Cardiac Electrophysiology Based on evaluation of QTc interval in an open-label, dose escalation and dose expansion study in 187 patients with cancer, erdafitinib had no large effect (i.e., > 20 ms) on the QTc interval. Serum Phosphate FGFR inhibition by BALVERSA increases serum phosphate level [see Dosage and Administration (2.3) and Drug Interactions (7.1) ]. 12.3 Pharmacokinetics Following administration of BALVERSA 8 mg once daily, the mean (coefficient of variation [CV%]) erdafitinib steady-state maximum plasma concentration (C max ), area under the curve (AUC tau ), and minimum plasma concentration (C min ) were 1,399 ng/mL (51%), 29,268 ng∙h/mL (60%), and 936 ng/mL (65%), respectively. Following single and repeat once daily dosing of BALVERSA, erdafitinib exposure (C max and AUC) increased proportionally across the dose range of 0.5 to 12 mg (0.06 to 1.3 times the maximum approved recommended dose). Steady state was achieved after 2 weeks with once daily dosing with a mean accumulation ratio was 4-fold. Absorption Median time to achieve peak plasma concentration (t max ) was 2.5 hours (range: 2 to 6 hours). Effect of Food No clinically meaningful differences in erdafitinib exposure was observed following administration of BALVERSA with a high-fat and high-calorie meal (800 calories to 1,000 calories with approximately 50% of total caloric content of the meal from fat). Distribution The mean apparent volume of distribution of erdafitinib was 29 L. Erdafitinib protein binding was 99.7% in patients, primarily to alpha-1-acid glycoprotein. Elimination The mean total apparent clearance (CL/F) of erdafitinib was 0.362 L/h. The mean effective half-life of erdafitinib was 59 hours. Metabolism Erdafitinib is primarily metabolized by CYP2C9 and CYP3A4. The contribution of CYP2C9 and CYP3A4 in the total clearance of erdafitinib is estimated to be 39% and 20%, respectively. Unchanged erdafitinib was the major drug-related moiety in plasma, there were no circulating metabolites. Excretion Following a single oral dose of radiolabeled erdafitinib, approximately 69% of the dose was recovered in feces (19% as unchanged) and 19% in urine (13% as unchanged). Specific Populations No clinically meaningful effects on erdafitinib exposure were observed based on age (21–92 years), sex, race (White, Hispanic or Asian), body weight (36–166 kg), mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment, or mild to moderate renal impairment (eGFR 30 to 89 mL/min/1.73 m²). Limited data are available in patients with severe (Child-Pugh C) hepatic impairment and in patients with severe renal impairment. The pharmacokinetics of erdafitinib in patients with renal impairment requiring dialysis is unknown. Drug Interaction Studies Clinical Studies Effect of Other Drugs on Erdafitinib Moderate CYP2C9 Inhibitors Erdafitinib mean ratios for C max and AUC inf were 121% and 148%, respectively, when BALVERSA was co-administered with fluconazole, a moderate CYP2C9 and CYP3A4 inhibitor, relative to BALVERSA administered alone. Strong CYP3A4 Inhibitors Erdafitinib mean ratios for C max and AUC inf were 105% and 134%, respectively, when BALVERSA was co-administered with itraconazole (a strong CYP3A4 inhibitor and P-gp inhibitor) relative to BALVERSA alone. CYP3A4/2C9 Inducers Erdafitinib mean ratios for C max and AUC inf were 78% and 45%, respectively, when BALVERSA was co-administered with carbamazepine (a strong CYP3A4 and weak CYP2C9 inducer) relative to BALVERSA alone. Effect of Erdafitinib on Other Drugs CYP3A4 Substrates: No clinically meaningful effect on the exposure of midazolam (a CYP3A4 substrate) was observed following coadministration with BALVERSA. OCT2 Substrates : No clinically meaningful effect on the exposure of metformin (an OCT2 substrate) was observed following coadministration with BALVERSA. In Vitro Studies CYP Substrates Erdafitinib is a time dependent inhibitor and inducer of CYP3A4. Erdafitinib is not an inhibitor of other major CYP isozymes at clinically relevant concentrations. Transporters Erdafitinib is a substrate and inhibitor of P-gp. P-gp inhibitors are not expected to affect erdafitinib exposure to a clinically relevant extent. Erdafitinib is an inhibitor of OCT2. Erdafitinib does not inhibit BCRP, OATP1B, OATP1B3, OAT1, OAT3, OCT1, MATE-1, or MATE-2K at clinically relevant concentrations. Acid-Lowering Agents Erdafitinib has adequate solubility across the pH range of 1 to 7.4. Acid-lowering agents (including antacids, H 2 -antagonists and proton pump inhibitors) are not expected to affect the bioavailability of erdafitinib. 12.5 Pharmacogenomics CYP2C9 activity is reduced in individuals with genetic variants, such as the CYP2C9*2 and CYP2C9*3 polymorphisms. Erdafitinib exposure was similar in subjects with CYP2C9*1/*2 and *1/*3 genotypes relative to subjects with CYP2C9*1/*1 genotype (wild type). No data are available in subjects characterized by other genotypes (e.g., *2/*2, *2/*3, *3/*3). Simulation suggested no clinically meaningful differences in erdafitinib exposure in subjects with CYP2C9*2/*2 and *2/*3 genotypes. The exposure of erdafitinib is predicted to be 50% higher in subjects with the CYP2C9*3/*3 genotype, estimated to be present in 0.4% to 3% of the population among various ethnic groups.

12.1 Mechanism of Action Erdafitinib is a kinase inhibitor that binds to and inhibits enzymatic activity of FGFR1, FGFR2, FGFR3 and FGFR4 based on in vitro data. Erdafitinib inhibited FGFR phosphorylation and signaling and decreased cell viability in cell lines expressing FGFR genetic alterations, including point mutations, amplifications, and fusions. Erdafitinib demonstrated antitumor activity in FGFR-expressing cell lines and xenograft models derived from tumor types, including bladder cancer.

12.2 Pharmacodynamics Cardiac Electrophysiology Based on evaluation of QTc interval in an open-label, dose escalation and dose expansion study in 187 patients with cancer, erdafitinib had no large effect (i.e., > 20 ms) on the QTc interval. Serum Phosphate FGFR inhibition by BALVERSA increases serum phosphate level [see Dosage and Administration (2.3) and Drug Interactions (7.1) ].

12.3 Pharmacokinetics Following administration of BALVERSA 8 mg once daily, the mean (coefficient of variation [CV%]) erdafitinib steady-state maximum plasma concentration (C max ), area under the curve (AUC tau ), and minimum plasma concentration (C min ) were 1,399 ng/mL (51%), 29,268 ng∙h/mL (60%), and 936 ng/mL (65%), respectively. Following single and repeat once daily dosing of BALVERSA, erdafitinib exposure (C max and AUC) increased proportionally across the dose range of 0.5 to 12 mg (0.06 to 1.3 times the maximum approved recommended dose). Steady state was achieved after 2 weeks with once daily dosing with a mean accumulation ratio was 4-fold. Absorption Median time to achieve peak plasma concentration (t max ) was 2.5 hours (range: 2 to 6 hours). Effect of Food No clinically meaningful differences in erdafitinib exposure was observed following administration of BALVERSA with a high-fat and high-calorie meal (800 calories to 1,000 calories with approximately 50% of total caloric content of the meal from fat). Distribution The mean apparent volume of distribution of erdafitinib was 29 L. Erdafitinib protein binding was 99.7% in patients, primarily to alpha-1-acid glycoprotein. Elimination The mean total apparent clearance (CL/F) of erdafitinib was 0.362 L/h. The mean effective half-life of erdafitinib was 59 hours. Metabolism Erdafitinib is primarily metabolized by CYP2C9 and CYP3A4. The contribution of CYP2C9 and CYP3A4 in the total clearance of erdafitinib is estimated to be 39% and 20%, respectively. Unchanged erdafitinib was the major drug-related moiety in plasma, there were no circulating metabolites. Excretion Following a single oral dose of radiolabeled erdafitinib, approximately 69% of the dose was recovered in feces (19% as unchanged) and 19% in urine (13% as unchanged). Specific Populations No clinically meaningful effects on erdafitinib exposure were observed based on age (21–92 years), sex, race (White, Hispanic or Asian), body weight (36–166 kg), mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment, or mild to moderate renal impairment (eGFR 30 to 89 mL/min/1.73 m²). Limited data are available in patients with severe (Child-Pugh C) hepatic impairment and in patients with severe renal impairment. The pharmacokinetics of erdafitinib in patients with renal impairment requiring dialysis is unknown. Drug Interaction Studies Clinical Studies Effect of Other Drugs on Erdafitinib Moderate CYP2C9 Inhibitors Erdafitinib mean ratios for C max and AUC inf were 121% and 148%, respectively, when BALVERSA was co-administered with fluconazole, a moderate CYP2C9 and CYP3A4 inhibitor, relative to BALVERSA administered alone. Strong CYP3A4 Inhibitors Erdafitinib mean ratios for C max and AUC inf were 105% and 134%, respectively, when BALVERSA was co-administered with itraconazole (a strong CYP3A4 inhibitor and P-gp inhibitor) relative to BALVERSA alone. CYP3A4/2C9 Inducers Erdafitinib mean ratios for C max and AUC inf were 78% and 45%, respectively, when BALVERSA was co-administered with carbamazepine (a strong CYP3A4 and weak CYP2C9 inducer) relative to BALVERSA alone. Effect of Erdafitinib on Other Drugs CYP3A4 Substrates: No clinically meaningful effect on the exposure of midazolam (a CYP3A4 substrate) was observed following coadministration with BALVERSA. OCT2 Substrates : No clinically meaningful effect on the exposure of metformin (an OCT2 substrate) was observed following coadministration with BALVERSA. In Vitro Studies CYP Substrates Erdafitinib is a time dependent inhibitor and inducer of CYP3A4. Erdafitinib is not an inhibitor of other major CYP isozymes at clinically relevant concentrations. Transporters Erdafitinib is a substrate and inhibitor of P-gp. P-gp inhibitors are not expected to affect erdafitinib exposure to a clinically relevant extent. Erdafitinib is an inhibitor of OCT2. Erdafitinib does not inhibit BCRP, OATP1B, OATP1B3, OAT1, OAT3, OCT1, MATE-1, or MATE-2K at clinically relevant concentrations. Acid-Lowering Agents Erdafitinib has adequate solubility across the pH range of 1 to 7.4. Acid-lowering agents (including antacids, H 2 -antagonists and proton pump inhibitors) are not expected to affect the bioavailability of erdafitinib.

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13

3 DOSAGE FORMS AND STRENGTHS Tablets: 3 mg, 4 mg, and 5 mg. ( 3 ) Tablets: 3 mg: Yellow, round biconvex, film-coated, debossed with "3" on one side; and "EF" on the other side. 4 mg: Orange, round biconvex, film-coated, debossed with "4" on one side; and "EF" on the other side. 5 mg: Brown, round biconvex, film-coated, debossed with "5" on one side; and "EF" on the other side.

BALVERSA Erdafitinib CROSCARMELLOSE SODIUM MAGNESIUM STEARATE MANNITOL MEGLUMINE MICROCRYSTALLINE CELLULOSE GLYCERYL MONOCAPRYLOCAPRATE POLYVINYL ALCOHOL, UNSPECIFIED SODIUM LAURYL SULFATE TALC TITANIUM DIOXIDE FERRIC OXIDE YELLOW FERRIC OXIDE RED ERDAFITINIB ERDAFITINIB biconvex shaped 4;EF BALVERSA Erdafitinib CROSCARMELLOSE SODIUM MAGNESIUM STEARATE MANNITOL MEGLUMINE MICROCRYSTALLINE CELLULOSE GLYCERYL MONOCAPRYLOCAPRATE POLYVINYL ALCOHOL, UNSPECIFIED SODIUM LAURYL SULFATE TALC TITANIUM DIOXIDE FERRIC OXIDE YELLOW ERDAFITINIB ERDAFITINIB biconvex shaped 3;EF BALVERSA Erdafitinib CROSCARMELLOSE SODIUM MAGNESIUM STEARATE MANNITOL MEGLUMINE MICROCRYSTALLINE CELLULOSE GLYCERYL MONOCAPRYLOCAPRATE POLYVINYL ALCOHOL, UNSPECIFIED SODIUM LAURYL SULFATE TALC TITANIUM DIOXIDE FERRIC OXIDE YELLOW FERRIC OXIDE RED FERROSOFERRIC OXIDE ERDAFITINIB ERDAFITINIB biconvex shaped 5;EF

13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility Carcinogenicity studies have not been conducted with erdafitinib. Erdafitinib was not mutagenic in a bacterial reverse mutation (Ames) assay and was not clastogenic in an in vitro micronucleus or an in vivo rat bone marrow micronucleus assay. Fertility studies in animals have not been conducted with erdafitinib. In the 3-month repeat-dose toxicity study, erdafitinib showed effects on female reproductive organs (necrosis of the ovarian corpora lutea) in rats at an exposure less than the human exposure (AUC) at maximum recommended human dose.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility Carcinogenicity studies have not been conducted with erdafitinib. Erdafitinib was not mutagenic in a bacterial reverse mutation (Ames) assay and was not clastogenic in an in vitro micronucleus or an in vivo rat bone marrow micronucleus assay. Fertility studies in animals have not been conducted with erdafitinib. In the 3-month repeat-dose toxicity study, erdafitinib showed effects on female reproductive organs (necrosis of the ovarian corpora lutea) in rats at an exposure less than the human exposure (AUC) at maximum recommended human dose.

NDA212018

BALVERSA

Erdafitinib

59676-030

HUMAN PRESCRIPTION DRUG

ORAL

PRINCIPAL DISPLAY PANEL - 3 mg Tablet Bottle Carton NDC 59676-030-56 Balversa ® (erdafitinib) tablets 3 mg Each film-coated tablet contains 3 mg of erdafitinib. Rx only 56 film-coated tablets 3 mg Tablet Bottle Carton

Indications and Usage ( 1 ) 01/2024 Dosage and Administration ( 2.2 ), ( 2.3 ) 01/2024 Warnings and Precautions ( 5.1 ), ( 5.2 ) 01/2024

Product of Switzerland Manufactured for: Janssen Products, LP Horsham, PA 19044, USA Under license from Astex Therapeutics Limited. For patent information: www.janssenpatents.com ©2019 Janssen Pharmaceutical Companies

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). FGFR Genetic Alterations Advise patients that evidence of a susceptible FGFR3 mutation or gene fusion within the tumor specimen is necessary to identify patients for whom treatment is indicated [see Dosage and Administration (2.1) ] . Ocular Disorders Advise patients to contact their healthcare provider if they experience any visual changes [see Warnings and Precautions (5.1) ]. In order to prevent or treat dry eyes, advise patients to use artificial tear substitutes, hydrating or lubricating eye gels or ointments frequently, at least every 2 hours during waking hours [see Dosage and Administration (2.3) ]. Skin, Mucous or Nail Disorders Advise patients to contact their healthcare provider if they experience progressive or intolerable skin, mucous or nail disorders [see Adverse Reactions (6.1) ] . Hyperphosphatemia and Soft Tissue Mineralization Inform patients that BALVERSA may cause hyperphosphatemia and soft tissue mineralization. Advise patients to immediately inform their healthcare provider of painful skin lesions or any symptoms related to acute change in phosphate levels such as muscle cramps, numbness, or tingling around the mouth [see Warnings and Precautions (5.2) ] . Advise patients that their healthcare provider will assess their serum phosphate level between 14 and 21 days of initiating treatment and will adjust the dose if needed [see Warnings and Precautions (5.2) ] . Advise patients to restrict phosphate intake to 600–800 mg daily. During this initial phosphate-assessment period, advise patients to avoid concomitant use with agents that can alter serum phosphate levels. Advise patients that, after the initial phosphate assessment period, monthly phosphate level monitoring for hyperphosphatemia should be performed during treatment with BALVERSA [see Drug Interactions (7.1) ]. Drug Interactions Advise patients to inform their healthcare providers of all concomitant medications, including prescription medicines, over-the-counter drugs, and herbal products [see Drug Interactions (7.1 , 7.2) ] . Dosing Instructions Instruct patients to swallow the tablets whole once daily with or without food. If vomiting occurs any time after taking BALVERSA, advise patients to take the next dose the next day [see Dosage and Administration (2.2) ] . Missed Dose If a dose is missed, advise patients to take the missed dose as soon as possible. Resume the regular daily dose schedule for BALVERSA the next day. Extra tablets should not be taken to make up for the missed dose [see Dosage and Administration (2.3) ] . Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females to inform their healthcare providers of a known or suspected pregnancy [see Warnings and Precautions (5.3) and Use in Specific Populations (8.1) ] . Advise female patients of reproductive potential to use effective contraception during treatment and for one month after the last dose of BALVERSA. Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for one month after the last dose of BALVERSA [see Use in Specific Populations (8.3) ]. Lactation Advise females not to breastfeed during treatment with BALVERSA and for one month after the last dose [see Use in Specific Populations (8.2) ]. Infertility Advise females of reproductive potential that BALVERSA may impair fertility [see Use in Specific Populations (8.3) ].

14 CLINICAL STUDIES 14.1 Urothelial Carcinoma with Susceptible FGFR3 Genetic Alterations The efficacy of BALVERSA was evaluated in Study BLC3001 (NCT03390504) Cohort 1, a randomized, open-label, multicenter study in which 266 patients with advanced urothelial cancer harboring selected FGFR3 alterations were randomized 1:1 to receive BALVERSA (8 mg with titration up to 9 mg) versus chemotherapy (docetaxel 75 mg/m 2 once every 3 weeks or vinflunine 320 mg/m 2 once every 3 weeks) until unacceptable toxicity or progression. Randomization was stratified by region (North America vs. Europe vs. rest of world), Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1 vs. 2) and visceral or bone metastases (yes vs. no). All patients needed to have had disease progression after 1 or 2 prior treatments, at least 1 of which included a PD-1 or PD-L1 inhibitor. FGFR3 genetic alterations were identified from tumor tissue in a central laboratory by the QIAGEN therascreen ® FGFR RGQ RT-Polymerase Chain Reaction (PCR) kit in 75% of patients while the remainder (25%) were identified by local next generation sequencing (NGS) assays. The major efficacy outcome measures were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) assessed by investigator using RECIST (Response Evaluation Criteria in Solid Tumors) Version 1.1. The median age was 67 years (range: 32 to 86 years) and 71% were male; 54% were White, 29% Asian, 0.4% Black, 0.4% multiple races, 16% not reported; 2% were Hispanic/Latino; and baseline ECOG performance status was 0 (43%), 1 (48%), or 2 (9%). Eighty-one percent of patients had FGFR3 mutations, 17% had fusions, and 2% had both mutations and fusions. Ninety-five percent of patients had pure transitional cell carcinoma (TCC) and 5% had TCC with other histologic variants. The primary tumor location was the upper tract for 33% of subjects and lower tract for 67%; 74% of patients had visceral or bone metastases. Eighty-eight percent of patients received platinum-containing chemotherapy previously. PD-1 or PD-L1 inhibitor therapy was received only in the neoadjuvant or adjuvant setting in 7% of patients. Statistically significant improvements in OS, PFS, and ORR were demonstrated for BALVERSA compared with chemotherapy. Table 9 and Figures 1 and 2 summarize the efficacy results for BLC3001 Cohort 1. Table 9: Efficacy Results for Study BLC3001 Cohort 1 BALVERSA N=136 Chemotherapy N=130 All p-values reported are 2-sided and compared with 0.019 of the allocated alpha for the interim analysis. ORR = confirmed objective response (CR + PR) CI = Confidence Interval Overall Survival (OS) Number of events (%) 77 (56.6%) 78 (60.0%) Median Based on Kaplan-Meier estimates , months (95% CI) 12.1 (10.3, 16.4) 7.8 (6.5, 11.1) Hazard ratio Based on an unstratified Cox proportional hazard model (95% CI) 0.64 (0.47, 0.88) p-value Based on an unstratified log-rank test 0.0050 Progression-free survival (PFS) Number of events (%) 101 (74.3%) 90 (69.2%) Median , months (95% CI) 5.6 (4.4, 5.7) 2.7 (1.8, 3.7) Hazard ratio (95% CI) 0.58 (0.44, 0.78) p-value 0.0002 Objective response rate (ORR) ORR (95% CI) 35.3% (27.3, 43.9) 8.5% (4.3, 14.6) p-value p-value is estimated using Cochran-Haenszel (CMH) test with ECOG performance status (0 or 1 vs 2) as a stratification factor. <0.001 Complete response, CR (%) 5.1% 0.8% Partial response, PR (%) 30.1% 7.7% Figure 1: Kaplan-Meier Plot of Overall Survival (Study BLC3001 Cohort 1) Figure 2: Kaplan-Meier Plot of Progression-free Survival (Study BLC3001 Cohort 1) Figure 1 Figure 2 Study BLC3001 Cohort 2 Study BLC3001 (NCT03390504) Cohort 2 was a multicenter, open-label, randomized study in 351 patients with locally advanced or metastatic urothelial carcinoma with selected FGFR3 alterations who received 1 prior line of systemic therapy and no prior PD-1 or PD-L1 inhibitor. Patients were randomized 1:1 to receive BALVERSA (8 mg with titration up to 9 mg) or pembrolizumab 200 mg every 3 weeks. The study did not meet its major efficacy outcome measure for superiority of OS at the pre-specified final analysis. The OS hazard ratio (HR) was 1.18 (95% CI: 0.92, 1.51; p=0.18), median 10.9 (95% CI: 9.2, 12.6) months for BALVERSA versus 11.1 (95% CI: 9.7, 13.6) months for pembrolizumab [see Indications and Usage (1) ] . Study BLC2001 Study BLC2001 (NCT02365597) was a multicenter, open-label, single-arm study to evaluate the efficacy and safety of BALVERSA in patients with locally advanced or metastatic urothelial carcinoma (mUC). FGFR mutation status for screening and enrollment of patients was determined by a clinical trial assay (CTA). The efficacy population consists of a cohort of eighty-seven patients who were enrolled in this study with disease that had progressed on or after at least one prior chemotherapy and that had at least 1 of the following genetic alterations: FGFR3 gene mutations ( R248C , S249C , G370C , Y373C ) or FGFR gene fusions ( FGFR3-TACC3 , FGFR3-BAIAP2L1 , FGFR2-BICC1 , FGFR2-CASP7 ), as determined by the CTA performed at a central laboratory. Tumor samples from 69 patients were tested retrospectively by the QIAGEN therascreen ® FGFR RGQ RT-PCR Kit, which is the FDA-approved test for selection of patients with mUC for BALVERSA. Patients received a starting dose of BALVERSA at 8 mg once daily with a dose increase to 9 mg once daily in patients whose serum phosphate levels were below the target of 5.5 mg/dL between days 14 and 17; a dose increase occurred in 41% of patients. BALVERSA was administered until disease progression or unacceptable toxicity. The major efficacy outcome measures were ORR and duration of response (DoR), as determined by blinded independent review committee (BIRC) according to RECIST v1.1. The median age was 67 years (range: 36 to 87 years), 79% were male, and 74% were Caucasian. Most patients (92%) had a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Sixty-six percent of patients had visceral metastases. Eighty-four (97%) patients received at least one of cisplatin or carboplatin previously. Fifty-six percent of patients only received prior cisplatin-based regimens, 29% received only prior carboplatin-based regimens, and 10% received both cisplatin and carboplatin-based regimens. Three (3%) patients had disease progression following prior platinum-containing neoadjuvant or adjuvant therapy only. Twenty-four percent of patients had been treated with prior anti PD-L1/PD-1 therapy. Efficacy results are summarized in Table 10 and Table 11. ORR was 32.2%. Responders included patients who had previously not responded to anti PD-L1/PD-1 therapy. Table 10: Efficacy Results Endpoint BIRC BIRC: Blinded Independent Review Committee Assessment N=87 ORR = CR + PR CI = Confidence Interval ORR (95% CI) 32.2% (22.4, 42.0) Complete response (CR) 2.3% Partial response (PR) 29.9% Median DoR in months (95% CI) 5.4 (4.2, 6.9) Table 11: Efficacy Results by FGFR Genetic Alteration BIRC BIRC: Blinded Independent Review Committee Assessment ORR = CR + PR CI = Confidence Interval FGFR3 Point Mutation N=64 ORR (95% CI) 40.6% (28.6, 52.7) FGFR3 Fusion Both responders had FGFR3-TACC3_V1 fusion , One patient with a FGFR2-CASP7/FGFR3-TACC3_V3 fusion is reported in both FGFR2 fusion and FGFR3 fusion above N=18 ORR (95% CI) 11.1% (0, 25.6) FGFR2 Fusion N=6 ORR 0

8.5 Geriatric Use Of the 479 patients treated with BALVERSA in clinical studies, 40% of patients were less than 65 years old, 40% of patients were 65 years to 74 years old, and 20% were 75 years old and over. Patients 65 years of age and older treated with BALVERSA experienced a higher incidence of adverse reactions requiring treatment discontinuation than younger patients. In clinical trials, the incidence of treatment discontinuations of BALVERSA due to adverse reactions was 10% in patients younger than 65 years, 20% in patients ages 65–74 years, and 35% in patients 75 years or older. No overall difference in efficacy was observed between these patients and younger patients [see Clinical Studies (14.1) ].

8.4 Pediatric Use Safety and effectiveness of BALVERSA in pediatric patients have not been established. In 4 and 13-week repeat-dose toxicology studies in rats and dogs, toxicities in bone and teeth were observed at an exposure less than the human exposure (AUC) at the maximum recommended human dose. Chondroid dysplasia/metaplasia were reported in multiple bones in both species, and tooth abnormalities included abnormal/irregular denting in rats and dogs and discoloration and degeneration of odontoblasts in rats.

8.1 Pregnancy Risk Summary Based on the mechanism of action and findings in animal reproduction studies, BALVERSA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on BALVERSA use in pregnant women to inform a drug-associated risk. Oral administration of erdafitinib to pregnant rats during organogenesis caused malformations and embryo-fetal death at maternal exposures that were less than the human exposures at the maximum recommended human dose based on AUC (see Data ). Advise pregnant women and females of reproductive potential of the potential risk to the fetus. 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, loss, 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 2–4% and 15–20%, respectively. Data Animal Data In an embryo-fetal toxicity study, erdafitinib was orally administered to pregnant rats during the period of organogenesis. Doses ≥4 mg/kg/day (at total maternal exposures <0.1% of total human exposures at the maximum recommended human dose based on AUC) produced embryo-fetal death, major blood vessel malformations and other vascular anomalies, limb malformations (ectrodactyly, absent or misshapen long bones), an increased incidence of skeletal anomalies in multiple bones (vertebrae, sternebrae, ribs), and decreased fetal weight.

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on the mechanism of action and findings in animal reproduction studies, BALVERSA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on BALVERSA use in pregnant women to inform a drug-associated risk. Oral administration of erdafitinib to pregnant rats during organogenesis caused malformations and embryo-fetal death at maternal exposures that were less than the human exposures at the maximum recommended human dose based on AUC (see Data ). Advise pregnant women and females of reproductive potential of the potential risk to the fetus. 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, loss, 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 2–4% and 15–20%, respectively. Data Animal Data In an embryo-fetal toxicity study, erdafitinib was orally administered to pregnant rats during the period of organogenesis. Doses ≥4 mg/kg/day (at total maternal exposures <0.1% of total human exposures at the maximum recommended human dose based on AUC) produced embryo-fetal death, major blood vessel malformations and other vascular anomalies, limb malformations (ectrodactyly, absent or misshapen long bones), an increased incidence of skeletal anomalies in multiple bones (vertebrae, sternebrae, ribs), and decreased fetal weight. 8.2 Lactation Risk Summary There are no data on the presence of erdafitinib in human milk, or the effects of erdafitinib on the breastfed child, or on milk production. Because of the potential for serious adverse reactions from erdafitinib in a breastfed child, advise lactating women not to breastfeed during treatment with BALVERSA and for one month following the last dose. 8.3 Females and Males of Reproductive Potential BALVERSA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating treatment with BALVERSA. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with BALVERSA and for one month after the last dose. Males Advise male patients with female partners of reproductive potential to use effective contraception during treatment with BALVERSA and for one month after the last dose. Infertility Females Based on findings from animal studies, BALVERSA may impair fertility in females of reproductive potential [see Nonclinical Toxicology (13.1) ] . 8.4 Pediatric Use Safety and effectiveness of BALVERSA in pediatric patients have not been established. In 4 and 13-week repeat-dose toxicology studies in rats and dogs, toxicities in bone and teeth were observed at an exposure less than the human exposure (AUC) at the maximum recommended human dose. Chondroid dysplasia/metaplasia were reported in multiple bones in both species, and tooth abnormalities included abnormal/irregular denting in rats and dogs and discoloration and degeneration of odontoblasts in rats. 8.5 Geriatric Use Of the 479 patients treated with BALVERSA in clinical studies, 40% of patients were less than 65 years old, 40% of patients were 65 years to 74 years old, and 20% were 75 years old and over. Patients 65 years of age and older treated with BALVERSA experienced a higher incidence of adverse reactions requiring treatment discontinuation than younger patients. In clinical trials, the incidence of treatment discontinuations of BALVERSA due to adverse reactions was 10% in patients younger than 65 years, 20% in patients ages 65–74 years, and 35% in patients 75 years or older. No overall difference in efficacy was observed between these patients and younger patients [see Clinical Studies (14.1) ]. 8.6 CYP2C9 Poor Metabolizers CYP2C9*3/*3 Genotype: Erdafitinib plasma concentrations are predicted to be higher in patients with the CYP2C9*3/*3 genotype. Monitor for increased adverse reactions in patients who are known or suspected to have CYP2C9*3/*3 genotype [see Pharmacogenomics (12.5) ] .

16 HOW SUPPLIED/STORAGE AND HANDLING BALVERSA ® (erdafitinib) tablets are available in the strengths and packages listed below: 3 mg tablets: Yellow, round biconvex, film-coated, debossed with "3" on one side and "EF" on the other side. Bottle of 56-tablets with child resistant closure (NDC 59676-030-56). Bottle of 84-tablets with child resistant closure (NDC 59676-030-84). 4 mg tablets: Orange, round biconvex, film-coated, debossed with "4" on one side and "EF" on the other side. Bottle of 28-tablets with child resistant closure (NDC 59676-040-28). Bottle of 56-tablets with child resistant closure (NDC 59676-040-56). 5 mg tablets: Brown, round biconvex, film-coated, debossed with "5" on one side and "EF" on the other side. Bottle of 28-tablets with child resistant closure (NDC 59676-050-28). Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] .

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] .