Poteligeo Drug Information

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.

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). 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. If mild (Grade 1) rash occurs, consider topical corticosteroids. Infusion Reactions Permanently discontinue POTELIGEO for a life-threatening (Grade 4) infusion reaction.

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.

If an infusion reaction occurs, administer premedication (such as diphenhydramine and acetaminophen) for subsequent POTELIGEO infusions.

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 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.

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. The data described below reflect exposure to POTELIGEO in Study 0761-010, a randomized, open-label, actively controlled clinical trial for adult patients with MF or SS who received at least one prior systemic therapy. In the vorinostat arm, 135 patients (73%) subsequently crossed over to POTELIGEO for a total of 319 patients treated with POTELIGEO.

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.

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.

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. POTELIGEO was discontinued for adverse reactions in 18% of randomized patients, most often due to rash or drug eruption (7.1%). 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 Study 0761-010. 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.

Gastrointestinal disorders: Immune-mediated colitis Infections: Hepatitis B virus reactivation Cardiac disorders: Stress cardiomyopathy Skin and subcutaneous disorders: Granuloma

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.

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