BRIEF SUMMARY

SUTIMLIMAB-jone (Feb 2022)

Indn- To decrease the need for red blood transfusion due to hemolysis in cold agglutinin disease

Dosage- Injection: 1,100 mg/22 mL (50 mg/mL) in a single-dose vial Vaccinate against encapsulated bacteria at least two weeks prior to treatment.

 Weight-based dosage weekly for two weeks then every two weeks:                               For patients weighing 39 kg to less than 75 kg: 6,500 mg by intravenous infusion.

 For patients weighing 75 kg or more: 7,500 mg by intravenous infusion.

ADR-  Most common adverse reactions (incidence =10%) are respiratory tract infection, viral infection, diarrhea, dyspepsia, cough, arthralgia, arthritis, and peripheral edema.

CI-  contraindicated in patients with known hypersensitivity to sutimlimab-jome or any of the inactive ingredients.

WARNINGS-

 Serious Infections: Ensure patients are vaccinated against encapsulated bacteria. Monitor patients for early signs and symptoms of infections.

 Infusion-Related Reactions: Monitor patients for infusion-related reactions, interrupt if reaction occurs, and institute appropriate medical management as needed.

 Risk of Autoimmune Disease: Monitor patients for signs and symptoms and manage medically.

 Recurrent Hemolysis Discontinuation: Monitor patients for signs and symptoms of hemolysis if treatment when   interrupted.

Pat inform-

Serious Infections -  Advise patients of the potential increased risk of infections including infections caused by encapsulated bacteria such as Neisseria meningitides,

Streptococcus pneumoniae, and Haemophilus influenzae. These infections may be serious or life-threatening. Inform patients that they are required to receive vaccinations against these bacteria according to current medical guidelines prior to initiation of and during treatment 

===================================================================

U.S. FDA APPROVED DRUGS SURING 2022                                        

Serial No 5

Name of the Drug-    ENJAYMO

Active Ingredient -   Sulimlimab- jome

Pharmacological Classification- To decrease the need for red blood transfusion                                                             due to hemolysis in cold agglutinin disease                                                                                                                                                        Date of Approval-          2/4//22   

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use                                       ENJAYMO safely and effectively.                                                                                  See full prescribing information for ENJAYMO. ENJAYMO™ (sutimlimab-jome) injection, for intravenous use

Initial U.S. Approval: 2022

INDICATIONS AND USAGE

 ENJAYMO is a classical complement inhibitor indicated to decrease the need for red blood cell (RBC) transfusion due to hemolysis in adults with cold agglutinin disease (CAD).

ADVERSE REACTIONS

 Most common adverse reactions (incidence =10%) are respiratory tract infection, viral infection, diarrhea, dyspepsia, cough, arthralgia, arthritis, and peripheral edema.

CONTRAINDICATIONS-

 ENJAYMO is contraindicated in patients with known hypersensitivity to sutimlimab-jome or any of the inactive ingredients.

WARNINGS AND PRECAUTIONS-

• Serious Infections: Ensure patients are vaccinated against encapsulated bacteria. Monitor patients for early signs and symptoms of infections.

 • Infusion-Related Reactions: Monitor patients for infusion-related reactions, interrupt if reaction occurs, and institute appropriate medical management as needed.

 • Risk of Autoimmune Disease: Monitor patients for signs and symptoms and manage medically.

• Recurrent Hemolysis After ENJAYMO Discontinuation: Monitor patients for signs and symptoms of hemolysis if treatment with ENJAYMO is interrupted.

DOSAGE AND ADMINISTRATION-

 • Vaccinate against encapsulated bacteria at least two weeks prior to treatment.

 • Weight-based dosage weekly for two weeks then every two weeks:                               o For patients weighing 39 kg to less than 75 kg: 6,500 mg by intravenous infusion.

 o For patients weighing 75 kg or more: 7,500 mg by intravenous infusion.

 • See Full Prescribing Information for important preparation and administration instructions.

DOSAGE FORMS AND STRENGTHS-

 Injection: 1,100 mg/22 mL (50 mg/mL) in a single-dose vial 

PATIENT COUNSELING INFORMATION-

 Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Serious Infections -                                                                                                         Advise patients of the potential increased risk of infections including infections caused by encapsulated bacteria such as Neisseria meningitides,

Streptococcus pneumoniae, and Haemophilus influenzae. These infections may be serious or life-threatening. Inform patients that they are required to receive vaccinations against these bacteria according to current medical guidelines prior to initiation of and during treatment with ENJAYMO.

Educate patients on the symptoms of infections and advise them to seek immediate medical attention if any new symptoms of infection occur

Infusion-Related Reactions-                                                                                      Advise patients that administration of ENJAYMO may result in infusion-related reactions including hypersensitivity reactions.

Hypersensitivity reactions may be serious or life-threatening (e.g., anaphylaxis).

Educate patients on the symptoms of infusion-related reactions and advise them to seek medical attention if any new symptoms of infusion-related reactions occur .

Risk of Autoimmune Disease-                                                                                        Educate patients that there may be an increased risk of developing an autoimmune disease such as SLE during ENJAYMO therapy.

Advise patients on signs and symptoms of SLE and to report any new symptoms of SLE and seek medical attention 

Discontinuation-                                                                                                           Inform patients with CAD that they may develop hemolysis due to CAD when ENJAYMO is discontinued and that they should be monitored by their healthcare provider following ENJAYMO discontinuation 

Manufactured by: Bioverativ USA Inc. Waltham, MA 02451 A SANOFI COMPANY US License No. 2078 ©2022 Bioverativ USA Inc. All rights reserved.

CLINICAL PHARMACOLOGY

1. Mechanism of Action - 

Sutimlimab-jome is an immunoglobulin G (IgG), subclass 4 (IgG4) monoclonal antibody (mAb) that inhibits the classical complement pathway (CP) and specifically binds to complement protein component 1, s subcomponent (C1s), a serine protease which cleaves C4                                                                                   

3. Pharmacokinetics-                                                                                                   Following administration of the approved weight-based recommended dosages, the exposure of sutimlimab-jome increases proportionally over a dosage range of 60 mg/kg to 100 mg/kg by intravenous infusion (0.3 to 1.5 times the maximum approved recommended dosage based on 75 kg body weight).

Steady state was achieved by Week 7 after starting sutimlimab-jome treatment, with an accumulation ratio of less than 2.

Distribution-                                                                                                                 Sutimlimab-jome binds to C1s in the serum. The volume of distribution at steady state was approximately 5.8 L in patients with CAD

 Elimination -                                                                                                                 The terminal elimination half-life and clearance varies at different doses due to target-mediated drug disposition at lower sutimlimab-jome concentrations.

The terminal elimination half-life (t1/2ß) of sutimlimab-jome is 21 days with a clearance (CL) of approximately 0.14 L/day at the approved recommended dosage

Metabolism-                                                                                                             Sutimlimab-jome is a protein. It is generally recognized that antibodies are metabolized by degradation into small peptides and individual amino acids.

Specific Populations -                                                                                                       No clinically significant differences in the pharmacokinetics of sutimlimab-jome were observed based on sex, age (19 to 88 years of age), ethnicity (Japanese, non-Japanese), and mild to moderate renal impairment (30 to 89 mL/min/1.73 m2 measured by estimated glomerular filtration rate [eGFR]).

The effects of severe renal impairment and hepatic impairment on the pharmacokinetics of sutimlimab-jome are unknown.

Body weight-                                                                                                              Population pharmacokinetic analysis shows that sutimlimab-jome exposures decreased up to 59% for a patient weighing 98 kg and increased up to 57% for a patient weighing 50.5 kg as Reference ID: 4932699 9 compared with a patient weighing 72 kg.

The effect of body weight on pharmacokinetics has been integrated in the recommended dose regimen tiered by body weight.

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary -                                                                                        There are no available data on ENJAYMO use in pregnant women to evaluate for a drugassociated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Human immunoglobulin G (IgG) antibodies are known to cross the placental barrier; therefore, sutimlimab-jome may be transmitted from the mother to the developing 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.

2. Lactation- Risk Summary-                                                                                              There are no data on the presence of sutimlimab-jome in human milk, effects on the breastfed child, or the effects on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to sutimlimab-jome are unknown.

No conclusions can be drawn regarding whether or not ENJAYMO is safe for use during breastfeeding.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ENJAYMO and any potential adverse effects on the breastfed child from ENJAYMO or from the underlying maternal condition.

4. Pediatric Use Safety and effectiveness in pediatric patients have not been established.

5. Geriatric Use Of the 34 patients with CAD in clinical studies of ENJAYMO, 79% were 65 years of age and over including 32% who were 75 years of age and over.

No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.