POTELIGEO

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Dermatologic Toxicity [ see Warnings and Precautions (5.1) ]. Infusion Reactions [ see Warnings and Precautions (5.2) ]. Infections [ see Warnings and Precautions (5.3) ]. Autoimmune Complications [ see Warnings and Precautions (5.4) ]. Complications of Allogeneic HSCT after POTELIGEO [ see Warnings and Precautions (5.5) ]. The most common adverse reactions (reported in ≥20% of patients) are rash, infusion related reactions, fatigue, diarrhea, musculoskeletal pain, and upper respiratory tract infection ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Kyowa Kirin, Inc. at 1-844-768-3544 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial 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. Trial 1 The data described below reflect exposure to POTELIGEO in a randomized, open-label, actively controlled clinical trial for adult patients with MF or SS who received at least one prior systemic therapy [ see Clinical Studies (14) ]. Of 370 patients treated, 184 (57% with MF, 43% with SS) received POTELIGEO as randomized treatment and 186 (53% with MF, 47% with SS) received vorinostat. In the vorinostat arm, 135 patients (73%) subsequently crossed over to POTELIGEO for a total of 319 patients treated with POTELIGEO. POTELIGEO was administered at 1 mg/kg intravenously over at least 60 minutes on days 1, 8, 15, and 22 of the first 28-day cycle and on days 1 and 15 of subsequent 28-day cycles. Premedication (diphenhydramine, acetaminophen) was optional and administered to 65% of randomized patients for the first infusion. The comparator group received vorinostat 400 mg orally once daily, given continuously in 28-day cycles. Treatment continued until unacceptable toxicity or progressive disease. The median age was 64 years (range, 25 to 101 years), 58% of patients were male, 70% were white, and 99% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients had a median of 3 prior systemic therapies. The trial required an absolute neutrophil count (ANC) ≥1,500/µL (≥1,000/µL if bone marrow was involved), platelet count ≥100,000/µL (≥75,000/µL if bone marrow was involved), creatinine clearance >50 mL/min or serum creatinine ≤1.5 mg/dL, and hepatic transaminases ≤2.5 times upper limit of normal (ULN) (≤5 times ULN if lymphomatous liver infiltration). Patients with active autoimmune disease, active infection, autologous HSCT within 90 days, or prior allogeneic HSCT were excluded. During randomized treatment, the median duration of exposure to POTELIGEO was 5.6 months, with 48% (89/184) of patients with at least 6 months of exposure and 23% (43/184) with at least 12 months of exposure. The median duration of exposure to vorinostat was 2.8 months, with 22% (41/186) of patients with at least 6 months of exposure. Fatal adverse reactions within 90 days of the last dose occurred in 2.2% (7/319) of patients who received POTELIGEO as randomized or crossover treatment. Serious adverse reactions were reported in 36% (66/184) of patients randomized to POTELIGEO and most often involved infection (16% of patients; 30/184). Serious adverse reactions reported in >2% of patients randomized to POTELIGEO were pneumonia (5%), sepsis (4%), pyrexia (4%), and skin infection (3%); other serious adverse reactions, each reported in 2% of patients, included hepatitis, pneumonitis, rash, infusion related reaction, lower respiratory tract infection, and renal insufficiency. POTELIGEO was discontinued for adverse reactions in 18% of randomized patients, most often due to rash or drug eruption (7.1%). Common Adverse Reactions The most common adverse reactions (reported in ≥20% of patients randomized to POTELIGEO) were rash (including drug eruption), infusion related reactions, fatigue, diarrhea, upper respiratory tract infection and musculoskeletal pain. Other common adverse reactions (reported in ≥10% of patients randomized to POTELIGEO) included skin infection, pyrexia, nausea, edema, thrombocytopenia, headache, constipation, mucositis, anemia, cough and hypertension. Table 1 summarizes common adverse reactions having a ≥2% higher incidence with POTELIGEO than with vorinostat in Trial 1. Table 1: Common Adverse Reactions (≥10%) with ≥2% Higher Incidence in the POTELIGEO Arm Adverse Reactions by Body System Adverse reactions include groupings of individual preferred terms. , Includes adverse reactions reported up to 90 days after randomized treatment. POTELIGEO (N=184) Vorinostat (N=186) All Grades (%) ≥Grade 3 (%) All Grades (%) ≥Grade 3 (%) Rash/Drug Eruption includes: dermatitis (allergic, atopic, bullous, contact, exfoliative, infected), drug eruption, palmoplantar keratoderma, rash (generalized, macular, maculopapular, papular, pruritic, pustular), skin reaction, toxic skin eruption Upper Respiratory Tract Infection includes: laryngitis viral, nasopharyngitis, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection, viral upper respiratory tract infection Skin Infection includes: cellulitis, dermatitis infected, erysipelas, impetigo, infected skin ulcer, periorbital cellulitis, skin bacterial infection, skin infection, staphylococcal skin infection Musculoskeletal Pain includes: back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, pain in extremity Mucositis includes: aphthous stomatitis, mouth ulceration, mucosal inflammation, oral discomfort, oral pain, oropharyngeal pain, stomatitis Skin and Subcutaneous Tissue Disorders Rash, Including Drug Eruption 35 5 11 2 Drug Eruption 24 5 <1 0 Procedural Complications Infusion Related Reaction 33 2 0 0 Infections Upper Respiratory Tract Infection 22 0 16 1 Skin Infection 19 3 13 4 Musculoskeletal and Connective Tissue Disorders Musculoskeletal Pain 22 <1 17 3 General Disorders Pyrexia 17 <1 7 0 Gastrointestinal Mucositis 12 1 6 0 Other Common Adverse Reactions in ≥10% of POTELIGEO Arm Includes grouped terms , From 184 patients randomized to POTELIGEO General disorders: fatigue (31%), edema (16%) Gastrointestinal disorders: diarrhea (28%), nausea (16%), constipation (13%) Blood and lymphatic system disorders : thrombocytopenia (14%), anemia (12%) Nervous system disorders: headache (14%) Vascular disorders: hypertension (10%) Respiratory disorders: cough (11%) Adverse Reactions in ≥5% but <10% of POTELIGEO Arm , Infections: candidiasis (9%), urinary tract infection (9%), folliculitis (8%), pneumonia (6%), otitis (5%), herpesvirus infection (5%) Investigations: renal insufficiency (9%), hyperglycemia (9%), hyperuricemia (8%), weight increase (8%), weight decrease (6%), hypomagnesemia (6%) Psychiatric disorders: insomnia (9%), depression (7%) Skin and subcutaneous disorders: xerosis (8%), alopecia (7%) Nervous system disorders: dizziness (8%), peripheral neuropathy (7%) Metabolism and nutrition disorders: decreased appetite (8%) Respiratory disorders: dyspnea (7%) General disorders: chills (7%) Gastrointestinal disorders: vomiting (7%), abdominal pain (5%) Injury, poisoning and procedural complications: fall (6%) Musculoskeletal disorders: muscle spasms (5%) Cardiovascular disorders: arrhythmia (5%) Eye disorders: conjunctivitis (5%) Selected Other Adverse Reactions , Tumor lysis syndrome (<1%) Myocardial ischemia or infarction (<1%) Cardiac failure (<1%) Cytomegalovirus infection (<1%) Table 2 summarizes common treatment-emergent laboratory abnormalities having a ≥2% higher incidence with POTELIGEO than with vorinostat. Table 2: Common New or Worsening Laboratory Abnormalities (≥10%) with ≥2% Higher Incidence in the POTELIGEO Arm Laboratory Test Includes laboratory abnormalities, reported up to 90 days after treatment, that are new or worsening in grade or with worsening from baseline unknown. POTELIGEO (N=184) Vorinostat (N=186) All Grades (%) ≥Grade 3 (%) All Grades (%) ≥Grade 3 (%) Chemistry Albumin Decreased 34 2 27 3 Calcium Decreased 30 3 20 2 Uric Acid Increased 29 29 11 11 Phosphate Decreased 27 5 26 5 Magnesium Decreased 17 <1 8 <1 Glucose Decreased 14 0 8 <1 Calcium Increased 12 <1 8 <1 Hematology CD4 Lymphocytes Decreased Out of 99 evaluable recipients of POTELIGEO and 36 evaluable recipients of vorinostat. 63 43 17 8 Lymphocytes Decreased 31 16 12 4 White Blood Cells Decreased 33 2 18 2 Other common treatment-emergent laboratory abnormalities in the POTELIGEO arm included hyperglycemia (52%; 4% Grade 3-4), anemia (35%; 2% Grade 3-4), thrombocytopenia (29%, none Grade 3-4), aspartate transaminase (AST) increased (25%; 2% Grade 3-4), alanine transaminase (ALT) increased (18%; 1% Grade 3-4), alkaline phosphatase increased (17%; 0% Grade 3-4), and neutropenia (10%; 2% Grade 3-4). Grade 4 treatment-emergent laboratory abnormalities observed in ≥1% of the POTELIGEO arm included lymphopenia (5%), leukopenia (1%), and hypophosphatemia (1%). 6.2 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to POTELIGEO with the incidences of antibodies in other studies or to other products may be misleading. Among 313 patients treated with POTELIGEO and whose antibodies were tested, 44 (14.1%) tested positive for anti-mogamulizumab-kpkc antibodies. There was no identified clinically significant effect of anti-drug antibodies on pharmacokinetics, safety, or effectiveness of POTELIGEO. There were no positive neutralizing antibody responses. 6.3 Postmarketing Experience The following adverse reactions have been identified during post-approval use of POTELIGEO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Infections: Hepatitis B virus reactivation Cardiac disorders: Stress cardiomyopathy

4 CONTRAINDICATIONS None. None ( 4 ).

11 DESCRIPTION Mogamulizumab-kpkc is a recombinant humanized monoclonal antibody that targets CC chemokine receptor 4 (CCR4)-expressing cells. Mogamulizumab-kpkc is an IgG1 kappa immunoglobulin that has a calculated molecular mass of approximately 149 kDa. Mogamulizumab-kpkc is produced by recombinant DNA technology in Chinese hamster ovary cells. POTELIGEO (mogamulizumab-kpkc) injection is a sterile, ready-to-use, preservative-free, clear to slightly opalescent colorless solution in a single-dose vial for dilution prior to intravenous infusion. Each vial contains 20 mg of mogamulizumab-kpkc in 5 mL of solution. Each mL of solution contains 4 mg of mogamulizumab-kpkc and is formulated in: citric acid monohydrate (0.44 mg), glycine (22.5 mg), polysorbate 80 (0.2 mg), and Water for Injection, USP. May contain hydrochloric acid/sodium hydroxide to adjust pH to 5.5.

2 DOSAGE AND ADMINISTRATION 1 mg/kg as an intravenous infusion over at least 60 minutes on days 1, 8, 15, and 22 of the first 28-day cycle and on days 1 and 15 of each subsequent cycle ( 2 ). 2.1 Recommended Dosage The recommended dose of POTELIGEO is 1 mg/kg administered as an intravenous infusion over at least 60 minutes. Administer on days 1, 8, 15, and 22 of the first 28-day cycle, then on days 1 and 15 of each subsequent 28-day cycle until disease progression or unacceptable toxicity. Administer POTELIGEO within 2 days of the scheduled dose. If a dose is missed, administer the next dose as soon as possible and resume dosing schedule. Do not administer POTELIGEO subcutaneously or by rapid intravenous administration. Recommended Premedications Administer premedication with diphenhydramine and acetaminophen for the first POTELIGEO infusion. 2.2 Dose Modifications for Toxicity Dermatologic Toxicity Permanently discontinue POTELIGEO for life-threatening (Grade 4) rash or for any Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) [ see Warnings and Precautions (5.1) ]. If SJS or TEN is suspected, stop POTELIGEO and do not resume unless SJS or TEN has been excluded and the cutaneous reaction has resolved to Grade 1 or less. If moderate or severe (Grades 2 or 3) rash occurs, interrupt POTELIGEO and administer at least 2 weeks of topical corticosteroids. If rash improves to Grade 1 or less, POTELIGEO may be resumed [ see Warnings and Precautions (5.1) ]. If mild (Grade 1) rash occurs, consider topical corticosteroids. Infusion Reactions Permanently discontinue POTELIGEO for a life-threatening (Grade 4) infusion reaction [ see Warnings and Precautions (5.2) ]. Temporarily interrupt the infusion of POTELIGEO for mild to severe (Grades 1 to 3) infusion reactions and treat symptoms. Reduce the infusion rate by at least 50% when restarting the infusion after symptoms resolve. If reaction recurs and is unmanageable, discontinue infusion. [ see Warnings and Precautions (5.2) ]. If an infusion reaction occurs, administer premedication (such as diphenhydramine and acetaminophen) for subsequent POTELIGEO infusions. 2.3 Preparation and Administration Preparation Visually inspect drug product solution for particulate matter and discoloration prior to administration. POTELIGEO is a clear to slightly opalescent colorless solution. Discard the vial if cloudiness, discoloration, or particulates are observed. Calculate the dose (mg/kg) and number of vials of POTELIGEO needed to prepare the infusion solution based on patient weight. Aseptically withdraw the required volume of POTELIGEO into the syringe and transfer into an intravenous (IV) bag containing 0.9% Sodium Chloride Injection, USP. The final concentration of the diluted solution should be between 0.1 mg/mL to 3.0 mg/mL. Mix diluted solution by gentle inversion. Do not shake. Discard any unused portion left in the vial. The diluted solution is compatible with polyvinyl chloride (PVC) or polyolefin (PO) infusion bags. Administration Administer infusion solution over at least 60 minutes through an intravenous line containing a sterile, low protein binding, 0.22 micron (or equivalent) in-line filter. Do not mix POTELIGEO with other drugs. Do not co-administer other drugs through the same intravenous line. Storage of Diluted Solution After preparation, infuse the POTELIGEO solution immediately, or store under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 24 hours from the time of infusion preparation. Do not freeze. Do not shake.

1 INDICATIONS AND USAGE POTELIGEO is indicated for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy. POTELIGEO is a CC chemokine receptor type 4 (CCR4)-directed monoclonal antibody indicated for the treatment of adult patients with relapsed or refractory mycosis fungoides or Sézary syndrome after at least one prior systemic therapy ( 1 ).

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Mogamulizumab-kpkc is a defucosylated, humanized IgG1 kappa monoclonal antibody that binds to CCR4, a G protein-coupled receptor for CC chemokines that is involved in the trafficking of lymphocytes to various organs. Non-clinical in vitro studies demonstrate mogamulizumab-kpkc binding targets a cell for antibody-dependent cellular cytotoxicity (ADCC) resulting in depletion of the target cells. CCR4 is expressed on the surface of some T-cell malignancies and is expressed on regulatory T-cells (Treg) and a subset of Th2 T-cells. 12.2 Pharmacodynamics Mogamulizumab-kpkc exposure-response relationships and the time course of pharmacodynamics response are unknown. 12.3 Pharmacokinetics Mogamulizumab-kpkc pharmacokinetics (PK) was evaluated in patients with T-cell malignancies. Parameters are presented as the geometric mean [% coefficient of variation (%CV)] unless otherwise specified. Mogamulizumab-kpkc concentrations increased proportionally with dose over the dose range of 0.01 to 1.0 mg/kg (0.01 to 1 times the approved recommended dosage). Following repeated dosing of the approved recommended dosage, steady state concentrations were reached after 8 doses (12 weeks), and the systemic accumulation was 1.6-fold. At steady state, the peak concentration (C max,ss ) is 32 (68%) µg/mL, the trough concentration (C min,ss ) is 11 (239%) µg/mL, and AUC ss is 5,577 (125%) µg∙hr/mL. Distribution The central volume of distribution is 3.6 L (20%). Elimination The terminal half-life is 17 days (66%), and the clearance is 12 mL/h (84%). Specific Populations : No clinically significant changes in the PK of mogamulizumab-kpkc were observed based on age (range: 22 to 101 years), sex, ethnicity, renal impairment (creatinine clearance <90 mL/min, estimated by Cockcroft-Gault), mild (total bilirubin ≤ ULN and AST 1.5 to 3 times ULN and any AST) hepatic impairment, disease subtype (MF or SS), degree of CCR4 expression, or ECOG status. The effect of severe hepatic impairment (total bilirubin >3 times ULN and any AST) on mogamulizumab-kpkc PK is unknown. Drug Interaction Studies No drug interaction studies have been conducted with POTELIGEO.

12.1 Mechanism of Action Mogamulizumab-kpkc is a defucosylated, humanized IgG1 kappa monoclonal antibody that binds to CCR4, a G protein-coupled receptor for CC chemokines that is involved in the trafficking of lymphocytes to various organs. Non-clinical in vitro studies demonstrate mogamulizumab-kpkc binding targets a cell for antibody-dependent cellular cytotoxicity (ADCC) resulting in depletion of the target cells. CCR4 is expressed on the surface of some T-cell malignancies and is expressed on regulatory T-cells (Treg) and a subset of Th2 T-cells.

12.2 Pharmacodynamics Mogamulizumab-kpkc exposure-response relationships and the time course of pharmacodynamics response are unknown.

12.3 Pharmacokinetics Mogamulizumab-kpkc pharmacokinetics (PK) was evaluated in patients with T-cell malignancies. Parameters are presented as the geometric mean [% coefficient of variation (%CV)] unless otherwise specified. Mogamulizumab-kpkc concentrations increased proportionally with dose over the dose range of 0.01 to 1.0 mg/kg (0.01 to 1 times the approved recommended dosage). Following repeated dosing of the approved recommended dosage, steady state concentrations were reached after 8 doses (12 weeks), and the systemic accumulation was 1.6-fold. At steady state, the peak concentration (C max,ss ) is 32 (68%) µg/mL, the trough concentration (C min,ss ) is 11 (239%) µg/mL, and AUC ss is 5,577 (125%) µg∙hr/mL. Distribution The central volume of distribution is 3.6 L (20%). Elimination The terminal half-life is 17 days (66%), and the clearance is 12 mL/h (84%). Specific Populations : No clinically significant changes in the PK of mogamulizumab-kpkc were observed based on age (range: 22 to 101 years), sex, ethnicity, renal impairment (creatinine clearance <90 mL/min, estimated by Cockcroft-Gault), mild (total bilirubin ≤ ULN and AST 1.5 to 3 times ULN and any AST) hepatic impairment, disease subtype (MF or SS), degree of CCR4 expression, or ECOG status. The effect of severe hepatic impairment (total bilirubin >3 times ULN and any AST) on mogamulizumab-kpkc PK is unknown. Drug Interaction Studies No drug interaction studies have been conducted with POTELIGEO.

20230427

14

3 DOSAGE FORMS AND STRENGTHS Injection: 20 mg/5 mL (4 mg/mL) as a clear to slightly opalescent colorless solution in a single-dose vial. Injection: 20 mg/5 mL (4 mg/mL) solution in a single-dose vial ( 3 ).

POTELIGEO mogamulizumab-kpkc mogamulizumab mogamulizumab citric acid monohydrate glycine polysorbate 80 sodium hydroxide hydrochloric acid water

13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility No carcinogenicity or genotoxicity studies have been conducted with POTELIGEO. No specific studies have been conducted to evaluate potential effects of POTELIGEO on fertility. No mogamulizumab-kpkc -related toxic effects in the male and female reproductive organs were observed in sexually mature monkeys in repeat-dose toxicology studies up to 26 weeks in duration.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility No carcinogenicity or genotoxicity studies have been conducted with POTELIGEO. No specific studies have been conducted to evaluate potential effects of POTELIGEO on fertility. No mogamulizumab-kpkc -related toxic effects in the male and female reproductive organs were observed in sexually mature monkeys in repeat-dose toxicology studies up to 26 weeks in duration.

BLA761051

POTELIGEO

mogamulizumab-kpkc

42747-761

HUMAN PRESCRIPTION DRUG

INTRAVENOUS

PRINCIPAL DISPLAY PANEL - 4 mg/mL Vial Carton Rx only NDC 42747-761-01 POTELIGEO ® (mogamulizumab-kpkc) Injection 20 mg/5 mL (4 mg/mL) For Intravenous Infusion Single-dose vial. Discard unused portion. PRINCIPAL DISPLAY PANEL - 4 mg/mL Vial Carton

POTELIGEO ® (mogamulizumab-kpkc) Manufactured by: Kyowa Kirin, Inc. Princeton, NJ 08540 US License No. 2077

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Inform patients of the risk of the following adverse reactions that may require additional treatment and/or withholding or discontinuation of POTELIGEO including: Dermatological Toxicity: Advise patients to contact their healthcare provider immediately for new or worsening skin rash [ see Warnings and Precautions (5.1) ]. Advise patients that the rash can happen at any time while receiving POTELIGEO. Infusion Reactions: Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion reactions [ see Warnings and Precautions (5.2) ]. Infections: Advise patients to contact their health care provider for fever or other evidence of infection [ see Warnings and Precautions (5.3) ]. Autoimmune Complications: Advise patients to notify their healthcare provider of any history of autoimmune disease [ see Warnings and Precautions (5.4) ]. Complications of Allogeneic HSCT after POTELIGEO: Advise patients of potential risk of post-transplant complications [ see Warnings and Precautions (5.5) ]. Females of Reproductive Potential: Advise use of effective contraception during treatment with POTELIGEO and for 3 months following the last dose of POTELIGEO [ see Use in Specific Populations (8.3) ].

14 CLINICAL STUDIES Trial 1 A randomized, open-label, multicenter trial (Study 0761-010; NCT01728805) evaluated the efficacy of POTELIGEO in adult patients with MF or SS after at least one prior systemic therapy. The trial randomized 372 patients 1:1 to either POTELIGEO (186 patients; 56% with MF, 44% with SS) or vorinostat (186 patients; 53% with MF, 47% with SS). The trial included patients regardless of tumor CCR4 expression status and excluded patients with histologic transformation, prior allogeneic HSCT, autologous HSCT within 90 days, active autoimmune disease, or active infection. The trial required patients to have ANC ≥1,500/µL (≥1,000/µL if bone marrow was involved), platelet count ≥100,000/µL (≥75,000/µL if bone marrow was involved), creatinine clearance >50 mL/min or serum creatinine ≤1.5 mg/dL and hepatic transaminases ≤2.5 times ULN (≤5 times ULN if lymphomatous liver infiltration). The dose of POTELIGEO was 1 mg/kg administered intravenously over at least 60 minutes on days 1, 8, 15, and 22 of the first 28-day cycle and on days 1 and 15 of each subsequent cycle. Vorinostat was dosed at 400 mg orally once daily, continuously for 28-day cycles. Treatment continued until disease progression or unacceptable toxicity. Vorinostat-treated patients with disease progression or unacceptable toxicities were permitted to cross over to POTELIGEO. The median age was 64 years (range: 25 to 101), 58% of patients were male, and 70% were white. At study baseline, 38% had stage IB-II disease, 10% stage III, and 52% stage IV. The median number of prior systemic therapies was 3. In the POTELIGEO arm, baseline CCR4 expression status by immunohistochemistry was available in 140 patients (75%), of whom all had CCR4 detected on ≥1% of lymphocytes on skin biopsy, and 134/140 (96%) had CCR4 detected on ≥10% of the lymphocytes. CCR4 expression status was similar in the vorinostat arm. During randomized treatment, the median duration of exposure to POTELIGEO was 5.6 months (range: <1 to 45.3 months), with 48% of patients with at least 6 months of exposure and 23% with at least 12 months of exposure. The median duration of exposure to vorinostat was 2.8 months (range: <1 to 34.8 months), with 22% of patients with at least 6 months of exposure. Efficacy was based on investigator-assessed progression-free survival (PFS), which was defined as the time from the date of randomization until documented progression of disease or death. Other efficacy measures included overall response rate (ORR) based on global composite response criteria that combine measures from each disease compartment (skin, blood, lymph nodes and viscera). Responses required confirmation at two successive disease assessments, which included the modified Severity Weighted Assessment Tool, skin photographs, central flow cytometry, and computed tomography. The trial demonstrated that POTELIGEO significantly prolonged PFS compared to vorinostat (Table 3). The Kaplan-Meier curve for PFS by Investigator is shown in Figure 1. The estimated median follow-up for investigator-assessed PFS was 13 months in the POTELIGEO arm and 10.4 months in the vorinostat arm. By independent review committee assessment, the estimated median PFS was 6.7 months (95% CI, 5.6 to 9.4) in the POTELIGEO arm and 3.8 months (95% CI, 3.0 to 4.7) in the vorinostat arm (hazard ratio 0.64; 95% CI: 0.49, 0.84). Figure 1 Kaplan-Meier Curve for Progression-Free Survival per Investigator Table 3 also summarizes investigator-assessed confirmed response rates, overall and by disease compartment. The trial demonstrated improvement in ORR with POTELIGEO. Table 3 Efficacy of Randomized Treatment (Trial 1) Outcome per Investigator POTELIGEO N=186 Vorinostat N=186 CI=confidence interval; CR=complete response; NE=not estimable; PR=partial response PFS Number of events, n 110 131 Progressive disease 104 128 Death 6 3 Median PFS (95% CI) (months) Kaplan-Meier estimate. 7.6 (5.6, 10.2) 3.1 (2.8, 4.0) Hazard ratio (95% CI) Log rank p-value 0.53 (0.41, 0.69) <.001 Overall response rate (confirmed CR + PR), n (%) Based on Global Composite Response score. , Responses in blood and skin must have persisted for at least 4 weeks to be considered confirmed and were evaluated every 4 weeks for the first year. Responses in lymph nodes, visceral disease and overall were evaluated every 8 weeks for the first year. 52 (28) 9 (5) 95% CI (22, 35) (2, 9) P-value From Cochran-Mantel-Haenszel test adjusted for disease type, stage, and region. <.001 Duration of overall response (months) Median (95% CI) 13.9 (9.3, 18.9) 9.0 (4.6, NE) Confirmed best overall response CR, n (%) 4 (2) 0 (0) 95% CI (1, 5) (0, 2) PR, n (%) 47 (25) 9 (5) 95% CI (20, 33) (2, 9) Response by compartment (confirmed CR + PR) Blood n=124 n=125 Response rate, n (%) 83 (67) 23 (18) 95% CI (58, 75) (12, 26) Skin n=186 n=186 Response rate, n (%) 78 (42) 29 (16) 95% CI (35, 49) (11, 22) Lymph nodes n=136 n=133 Response rate, n (%) 21 (15) 5 (4) 95% CI (10, 23) (1, 9) Viscera n=6 n=4 Response rate, n (%) 0 (0) 0 (0) 95% CI (0, 46) (0, 60) Figure 1

8.5 Geriatric use Of 319 patients with MF or SS who received POTELIGEO in Trial 1, 162 (51%) were ≥65 years. No overall differences in effectiveness were observed between these patients and younger patients. In patients aged ≥65, Grade 3 or higher adverse reactions were reported in 45% and serious adverse reactions in 36%, whereas in patients aged <65, Grade 3 or higher adverse reactions were reported in 36% and serious adverse reactions in 29%.

8.4 Pediatric use The safety and effectiveness of POTELIGEO in pediatric patients have not been established.

8.1 Pregnancy Risk Summary There are no available data on POTELIGEO use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In an animal reproduction study, administration of mogamulizumab-kpkc to pregnant cynomolgus monkeys from the start of organogenesis through delivery did not show a potential for adverse developmental outcomes at maternal systemic exposures 27 times the exposure in patients at the recommended dose, based on AUC ( see Data ). In general, IgG molecules are known to cross the placental barrier and in the monkey reproduction study mogamulizumab-kpkc was detected in fetal plasma. Therefore, POTELIGEO has the potential to be transmitted from the mother to the developing fetus. POTELIGEO is not recommended during pregnancy or in women of childbearing potential not using contraception. 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 risks of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively. Data Animal Data The effects of mogamulizumab-kpkc on embryo-fetal development were evaluated in 12 pregnant cynomolgus monkeys that received mogamulizumab-kpkc once weekly by intravenous administration from the start of organogenesis through delivery at an exposure level 27 times higher than the clinical dose. Mogamulizumab-kpkc administration did not show a potential for embryo-fetal lethality, teratogenicity, or fetal growth retardation and did not result in spontaneous abortion or increased fetal death. In surviving fetuses (10 of 12 compared with 11 of 12 in the control group) of cynomolgus monkeys treated with mogamulizumab-kpkc, a decrease in CCR4-expressing lymphocytes due to the pharmacological activity of mogamulizumab-kpkc was noted; there were no apparent mogamulizumab-kpkc -related external, visceral, or skeletal abnormalities.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no available data on POTELIGEO use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In an animal reproduction study, administration of mogamulizumab-kpkc to pregnant cynomolgus monkeys from the start of organogenesis through delivery did not show a potential for adverse developmental outcomes at maternal systemic exposures 27 times the exposure in patients at the recommended dose, based on AUC ( see Data ). In general, IgG molecules are known to cross the placental barrier and in the monkey reproduction study mogamulizumab-kpkc was detected in fetal plasma. Therefore, POTELIGEO has the potential to be transmitted from the mother to the developing fetus. POTELIGEO is not recommended during pregnancy or in women of childbearing potential not using contraception. 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 risks of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively. Data Animal Data The effects of mogamulizumab-kpkc on embryo-fetal development were evaluated in 12 pregnant cynomolgus monkeys that received mogamulizumab-kpkc once weekly by intravenous administration from the start of organogenesis through delivery at an exposure level 27 times higher than the clinical dose. Mogamulizumab-kpkc administration did not show a potential for embryo-fetal lethality, teratogenicity, or fetal growth retardation and did not result in spontaneous abortion or increased fetal death. In surviving fetuses (10 of 12 compared with 11 of 12 in the control group) of cynomolgus monkeys treated with mogamulizumab-kpkc, a decrease in CCR4-expressing lymphocytes due to the pharmacological activity of mogamulizumab-kpkc was noted; there were no apparent mogamulizumab-kpkc -related external, visceral, or skeletal abnormalities. 8.2 Lactation Risk Summary There is no information regarding the presence of POTELIGEO in human milk, the effects on the breastfed child, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for POTELIGEO and any potential adverse effects on the breastfed child from POTELIGEO or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential POTELIGEO is not recommended during pregnancy or in women of childbearing potential not using contraception. Pregnancy Testing For females of reproductive potential, verify pregnancy status prior to initiating POTELIGEO. Contraception Advise females of reproductive potential to use effective contraception during treatment with POTELIGEO and for 3 months following the last dose of POTELIGEO. 8.4 Pediatric use The safety and effectiveness of POTELIGEO in pediatric patients have not been established. 8.5 Geriatric use Of 319 patients with MF or SS who received POTELIGEO in Trial 1, 162 (51%) were ≥65 years. No overall differences in effectiveness were observed between these patients and younger patients. In patients aged ≥65, Grade 3 or higher adverse reactions were reported in 45% and serious adverse reactions in 36%, whereas in patients aged <65, Grade 3 or higher adverse reactions were reported in 36% and serious adverse reactions in 29%.

16 HOW SUPPLIED/STORAGE AND HANDLING POTELIGEO (mogamulizumab-kpkc) injection is a sterile, preservative-free, clear to slightly opalescent colorless solution supplied in a carton containing one 20 mg/5 mL (4 mg/mL), single-dose glass vial (NDC 42747-761-01). Store vials under refrigeration at 2°C to 8°C (36°F to 46°F) in original package to protect from light until time of use. Do not freeze. Do not shake.

Store vials under refrigeration at 2°C to 8°C (36°F to 46°F) in original package to protect from light until time of use. Do not freeze. Do not shake.