sutimlimab (Rx)

>10%

Urinary tract infection (38%)

Fatigue (33%)

Dizziness (29%)

Peripheral edema (25%)

Respiratory tract infection (25%)

Bacterial infection (25%)

Arthralgia (25%)

Hypertension (23-25%)

Nausea (25%)

Cough (25%)

Headache (21-23%)

Pyrexia (21%)

Nasopharyngitis (21%)

Viral infection (21%)

Abdominal pain (21%)

Acrocyanosis (18-21%)

Rhinitis (18%)

Raynaud’s phenomenon (18%)

Infusion-related reaction (17%)

Contraindications

Hypersensitivity to sutimlimab or inactive ingredients

Cautions

Monitor for infusion-related reactions and interrupt if reaction occurs; discontinue infusion and institute appropriate supportive measures if signs of hypersensitivity reactions (eg, cardiovascular instability, respiratory compromise) occur

May potentially increase the risk of developing autoimmune diseases such as systemic lupus erythematosus; monitor for signs and symptoms and manage medically

Monitor for signs and symptoms of hemolysis such as elevated levels of total bilirubin or lactate dehydrogenase accompanied by decreased hemoglobin, or reappearance of symptoms such as fatigue, dyspnea, palpitations, or hemoglobinuria; consider restarting infusion if signs and symptoms of hemolysis occur after discontinuing

Serious infections

• May increase susceptibility to serious infections, including infections caused by encapsulated bacteria such as Neisseria meningitidis (any serogroup), Streptococcus pneumoniae, and Haemophilus influenzae
• Serious bacterial and viral infections were reported; infections included sepsis and respiratory and skin infections
• Vaccination reduces but does not eliminate, risk of encapsulated bacterial infections;some infections may become rapidly life-threatening or fatal if not recognized or treated promptly
• Inform patients of signs and symptoms of infections and steps to be taken to seek immediate care
• Vaccinate patients for encapsulated bacteria according to the most current ACIP recommendations for patients with persistent complement deficiencies; revaccinate patients in accordance with ACIP recommendations
• Immunize patients without a history of vaccination against encapsulated bacteria at ≥2 weeks before receiving initial dose
• If urgent therapy indicated in unvaccinated patient, administer vaccine(s) as soon as possible
• If administered to patients with active systemic infections, monitor closely for signs and symptoms of worsening infection
• Consider treatment interruption in patients undergoing treatment for serious infection
• Not studied in patients with chronic systemic infections such as hepatitis B, hepatitis C, or HIV

Pregnancy

No data are available on use in pregnant females to evaluate for a drug-associated 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

Animal data

• IV administration of sutimlimab to pregnant monkeys during organogenesis at doses 2 to 3 times the maximum recommended human doses did not result in adverse effects on pregnancy or offspring development

Lactation

There are no data on the presence of sutimlimab-jome in human milk, its effects on breastfed children, or its effects on milk production

Maternal IgG is known to be present in human milk

Effects of local gastrointestinal exposure and limited systemic exposure in breastfed children to sutimlimab-jome are unknown

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Immunoglobulin G (IgG), subclass 4 (IgG4) monoclonal antibody (mAb)

Inhibition of the classic complement pathway at the level of C1s prevents deposition of complement opsonins on the surface of RBCs, resulting in inhibition of hemolysis in patients with CAD

Absorption

Steady-state reached at Week 7

Accumulation ratio: <2

Distribution

Vd: 5.8 L

Sutimlimab binds to C1s in serum

Metabolism

Metabolized by degradation into small peptides and individual amino acids

Elimination

Clearance: 0.14 L/day

Half-life: 21 days

IV Incompatibilities

Infusion bags

• Di-(2-ethylhexyl)phthalate plasticized (DEHP) polyvinyl chloride (PVC)
• Ethyl vinyl acetate
• Polyolefin

Administration sets

• DEHP-plasticized PVC
• DEHP-free polypropylene
• Polyethylene

Vial adapters

• Polycarbonate
• Acrylonitrile-butadiene-styrene

IV Compatibilities

0.9% NaCl

IV Preparation

Each vial is for single dose only

Remove vials from refrigerator; to minimize foaming, do not shake

Visually inspect all drug vials and products for particulates and discoloration before administering

Drug solution is clear to slightly opalescent and colorless to slightly yellow liquid; discard if discolored or if other foreign particulates are present

Undiluted preparation

• Withdraw calculated volume from vials based on recommended dose

  • 39 to <75 kg: 6,500 mg (130 mL undiluted drug)
  • ≥75 kg: 7,500 mg (150 mL undiluted drug)
  • Add drug to an empty infusion bag

Diluted preparation

• Withdraw calculated volume from appropriate number of vials and dilute with 0.9% NaCl to total volume of 500 mL
• 39 to <75 kg: 6,500 mg (130 mL) dilute with 0.9% NaCl 370 mL
• ≥75 kg: 7,500 mg (150 mL) dilute with 0.9% NaCl 350 mL
• If not used immediately, refrigerate at 2-8ºC (36-46ºF)
• Once removed from refrigerator, allow diluted solution to adjust to room temperature 20- 25ºC (68-77ºF) and administer within 8 hr

IV Administration

Administer infusion only through a 0.2-micron inline filter with a polyethersulfone (PES) membrane

Prime infusion catheter and tubing with the dosing solution immediately before infusion and flush immediately after completing infusion with ~20 mL of sterile 0.9% NaCl

Maximum infusion rate for undiluted preparation

• 6,500 mg-dose: 130 mL/hr
• 7,500 mg-dose: 150 mL/hr
• Patients with cardiopulmonary disease for any dose: Infuse over 120 min

Maximum infusion rate for diluted preparation

• 6,500-mg dose (39 kg to <70 kg): 250 mL/hr
• 6,500-mg dose (70 to <75 kg): 500 mL/hr
• 7,500-mg dose: 500 mL/hr
• Patients with cardiopulmonary disease for any dose: Infuse over 120 min

Infusion-related reactions

• Slow or stop infusion if infusion reaction occurs
• Initial infusion: Monitor for ≥2 hr after completing infusion for signs or symptoms of an infusion and/or hypersensitivity reaction
• Subsequent infusions: Monitor for 1 hr after completing infusion for signs or symptoms of an infusion reaction

Missed dose

• Missed dose: Administer as soon as possible; thereafter, resume dosing q2Weeks
• If last dose >17 days, administer dose weekly for 2 weeks, then q2Weeks thereafter

Storage

Unused vials

• Refrigerate at 2-8ºC (36-46ºF) in original carton to protect from light
• Do not freeze
• Do not shake
• Discard unused portion

Diluted solution

• If not used immediately, refrigerate at 2-8ºC (36-46ºF)
• Once removed from refrigerator, allow diluted solution to adjust to room temperature 20- 25ºC (68-77ºF) and administer within 8 hr
• Do not exceed 36 hr total from time of preparation, including refrigeration, adjustment to room temperature, and expected infusion time
• May use in-line infusion warmers, do not exceed temperature of 40ºC (104ºF)