Drug Interaction Studies-                                                                                                    No drug interaction studies have been conducted with POTELIGEO. 

BRIEF SUMMARY

MOGAMULLIZUMAB- (Aug 2018)

Indn-   to treat two types of non-Hodgkin lymphoma,.  

Comp-   Injection: 20 mg/5 mL (4 mg/mL) solution in a single-dose vial  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  

ADR-   The most common adverse reactions (reported in =20% of patients) were rash, infusion related reactions, fatigue, diarrhea, musculoskeletal pain, and upper respiratory tract infection

CI-   None

WARNINGS-                                                                                                   Dermatologic Toxicity:                                                                                                  Temporarily interrupt for moderate or severe skin rashes. Permanently discontinue  for life-threatening rash

 Infusion Reactions:                                                                                                         Temporarily interrupt for any infusion reaction. Permanently discontinue  for any life-threatening infusion reaction

Pat Inform-                                                                                                                     Inform patients of the risk of the following adverse reactions that may require additional treatment and/or withholding or discontinuation of  including:

 Dermatological Toxicity: Advise patients to contact their healthcare provider immediately for new or worsening skin rash. Advise patients that the rash can happen at any time while receiving.

 Infusion Reactions: Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion reactions 

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U.S. FDA APPROVED  DRUGS DURING 2018

Sr.No-  27

ADVERSE REACTIONS-

 The most common adverse reactions (reported in =20% of patients) were rash, infusion related reactions, fatigue, diarrhea, musculoskeletal pain, and upper respiratory tract infection

CONTRAINDICATIONS-                                                                                                     None

WARNINGS AND PRECAUTIONS-

 ? Dermatologic Toxicity:                                                                                                  Temporarily interrupt POTELIGEO for moderate or severe skin rashes. Permanently discontinue POTELIGEO for life-threatening rash

? Infusion Reactions:                                                                                                         Temporarily interrupt POTELIGEO for any infusion reaction. Permanently discontinue POTELIGEO for any life-threatening infusion reaction

 ? Infections:                                                                                                                        Monitor and treat promptly

 ? Autoimmune Complications:                                                                                          Interrupt or permanently discontinue POTELIGEO as appropriate

 ? Complications of Allogeneic HSCT after POTELIGEO:                                                Monitor for severe acute graft-versus-host disease (GVHD) and steroid-refractory GVHD. Transplant-related mortality has occurred.

 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. 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                  

 Infections: Advise patients to contact their health care provider for fever or other evidence of infection.

 Autoimmune Complications: Advise patients to notify their healthcare provider of any history of autoimmune disease    

 Complications of Allogeneic HSCT after POTELIGEO: Advise patients of potential risk of post-transplant complications

  Females of Reproductive Potential:                                                                             Advise use of effective contraception during treatment with POTELIGEO and for at least 3 months following the last dose of POTELIGEO

POTELIGEO® (mogamulizumab-kpkc)                                                         Manufactured by:  Kyowa Kirin, Inc.  Bedminster, NJ 07921 US L

CLINICAL PHARMACOLOGY-

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 Tcell malignancies and is expressed on regulatory T-cells (Treg) and a subset of Th2 T-cells.   

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

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 (Cmax,ss) is 32 (68%) µg/mL, the trough concentration (Cmin,ss) is 11 (239%) µg/mL, and AUCss 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%).    

 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. 

USE IN SPECIFIC POPULATIONS-

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 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. 

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.

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 at least 3 months following the last dose of POTELIGEO.  

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

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%.