FDA Approves POTELIGEO (Mogamulizumab-kpkc) for Treatment of Adult Patients with Relapsed or Refractory Mycosis Fungoides or Sézary Syndrome After At Least One Prior Systemic Therapy 

On August 8, 2018, the U.S Food and Drug Administration (FDA) approved POTELIGEO® (mogamulizumab-kpkc) injection for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy. The approved recommended dosage of POTELIGEO is 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 28-day cycle until disease progression or unacceptable toxicity. Administer POTELIGEO within 2 days of the scheduled dose. Premedicate with diphenhydramine and acetaminophen for the first POTELIGEO infusion.

Fatal and life-threatening skin adverse reactions, infusion reactions, infections, and immune-mediated complications have occurred with POTELIGEO. Transplant complications have been reported in patients who received allogenic hematopoietic stem cell transplantation (HSCT). Additional information regarding these warnings and precautions and their management can be found in the full prescribing information linked below.

Mechanism of Action (MOA) and Pharmacokinetics (PK)

  • MOA: Mogamulizumab-kpkc is a CC chemokine receptor type 4 (CCR4)-directed monoclonal antibody that targets a cell for antibody-dependent cellular cytotoxicity (ADCC) resulting in depletion of the target cells in non-clinical studies.
  • General PK: Steady state concentrations were reached after 8 approved recommended doses (12 weeks), and the systemic accumulation was 1.6-fold. Mogamulizumab-kpkc concentrations increased proportionally over the dose range of 0.01 to 1.0 mg/kg (0.01 to 1 times the approved recommended dosage) in patients with T-cell malignancies. The geometric mean (%CV) of the peak concentration is 32 (68%) μg/mL, the trough concentration is 11 (239%) μg/mL, and steady state AUC is 5577 (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%).
  • Immunogenicity: Among 258 patients treated with POTELIGEO in a clinical trial, 10 (3.9%) tested positive for treatment-emergent (treatment-induced or treatment-boosted) anti-mogamulizumab-kpkc antibodies by an electrochemiluminescent assay. There were no positive neutralizing antibody responses.

Use in 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 < ULN, or total bilirubin < 1 to 1.5 times ULN and any AST) or moderate (total bilirubin >1.5 to 3 times ULN and any AST) hepatic impairment, disease subtype (MF or SS), degree of CCR4 expression, or Eastern Cooperative Oncology Group (ECOG) status. The effect of severe hepatic impairment (total bilirubin > 3 times ULN and any AST) on mogamulizumab-kpkc PK is unknown.

Efficacy and Safety

Efficacy of POTELIGEO was demonstrated in a randomized, multicenter, open-label trial which compared the approved recommended dosage of POTELIGEO to vorinostat in adult patients with MF or SS after at least one prior systemic therapy. Additional information regarding the efficacy trial can be found in the full prescribing information linked below.

The most common adverse reactions (incidence ≥ 20%) were rash, infusion related reactions, fatigue, diarrhea, musculoskeletal pain, and upper respiratory tract infection.

Full prescribing information is available at https://go.usa.gov/xPrsD.  

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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.