pegcetacoplan (Rx)

>10%

Infusion-site reactions (39%)

Infection (29%)

Diarrhea (22%)

Abdominal pain (20%)

Respiratory tract infection (15%)

Viral infection (12%)

Fatigue (12%)

1-10%

Chest pain (7%)

Back pain (7%)

Headache (7%)

Systemic hypertension (7%)

Intestinal ischemia (<5%)

Biliary sepsis (<5%)

Hypersensitivity pneumonitis (<5%)

Contraindications

Hypersensitivity to pegcetacoplan or to any of the excipients

Patients not vaccinated against certain encapsulated bacteria, unless the risks of delaying pegcetacoplan treatment outweigh risks of developing a bacterial infection with an encapsulated organism

Patients with unresolved serious infection caused by encapsulated bacteria, including S pneumoniae, N meningitidis, and H influenzae

Cautions

Available only through restricted access program

Infusion-related reactions reported, including systemic hypersensitivity reactions (eg, facial swelling, rash, urticaria); discontinue infusion immediately and provide appropriate treatment, per standard of care, if severe hypersensitivity reaction, including anaphylaxis, occurs; monitor until signs and symptoms resolve

Serious infections caused by encapsulated bacteria

• May increase risk for serious infections caused by encapsulated bacteria
• All patients must be vaccinated against these bacteria according to the most current ACIP recommendations for patients with altered immunocompetence associated with complement deficiencies
• Revaccinate patients in accordance with ACIP recommendations considering the duration of therapy
• If vaccination history unknown, administer required vaccines at least 2 weeks before first pegcetacoplan dose
• If immediate therapy with pegcetacoplan indicated, administer required vaccine as soon as possible and provide patients with 2 weeks of antibacterial drug prophylaxis
• Closely monitor for infection

Monitoring after discontinuation

• Closely monitor for signs and symptoms of hemolysis, identified by elevated LDH levels along with sudden decrease in PNH clone size or hemoglobin, or reappearance of symptoms (eg, fatigue, hemoglobinuria, abdominal pain, dyspnea, major adverse vascular events [including thrombosis], dysphagia, erectile dysfunction)
• Monitor for at least 8 weeks to detect hemolysis and other reactions
• If hemolysis, including elevated LDH, occurs, consider restarting treatment

Interference with laboratory tests

• Drug may interfere with silica reagents in coagulation panels that results in artificially prolonged activated partial thromboplastin time; avoid silica reagents in coagulation panels

Pregnancy

Insufficient data regarding use in pregnant females to inform of drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

There are risks to the mother and fetus associated with untreated PNH during pregnancy

Animal studies

• Treatment of pregnant cynomolgus monkeys (28 mg/kg/day SC) (2.9 times human exposure based on AUC) from gestation through parturition resulted in a statistically significant increase in abortions or stillbirths compared with controls

Clinical considerations

• PNH in pregnancy associated with adverse maternal outcomes, including worsening cytopenias, thrombotic events, infections, bleeding, miscarriages, and increased maternal mortality, and adverse fetal outcomes, including fetal death and premature delivery

Contraception

• May cause embryofetal harm when administered to pregnant females
• Pregnancy testing recommended for females of reproductive potential before treatment
• Advise female patients of reproductive potential to use effective contraception during treatment and for 40 days after last dose

Lactation

Unknown if secreted in human milk or whether there is potential for absorption and harm to the infant

There are no data on effects on milk production

Pegcetacoplan is present in milk of lactating monkeys; since many medicinal products are secreted into human milk, and the potential exists for serious adverse reaction in a breastfeeding child, breastfeeding should be discontinued during treatment and for 40 days after the last dose

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

Binds to complement protein C3 and its activation fragment C3b, thereby regulating C3 cleavage and generation of downstream effectors of complement activation

In PNH, extravascular hemolysis (EVH) is facilitated by C3b opsonization while intravascular hemolysis (IVH) is mediated by the downstream membrane attack complex

Pegcetacoplan acts proximally in the complement cascade controlling both C3b-mediated EVH and terminal complement-mediated IVH

Absorption

Peak plasma time: 108-144 hr (4.5-6 days)

Trough serum concentration (steady-state): 655-706 mcg/mL (at 16 weeks)

Steady-state achieved ~4-6 weeks

Distribution

Vd: ~3.9 L

Metabolism

Expected to be metabolized into small peptides and amino acids by catabolic pathways

Elimination

Half-life: 8 days

Clearance: 0.37 L/day

SC Preparation

Allow pegcetacoplan to reach room temperature for ~30 minutes; keep vial in carton until ready for use to protect from light

Visually inspect for particulate matter and discoloration prior to use; solution should appear clear, colorless to slightly yellowish; discard if cloudy, contains particles, or is dark yellow

Use needleless transfer device (eg, vial adapter) or transfer needle to fill syringe

Refer to prescribing information and infusion pump instructions for full details

SC Administration

Infuse via commercially available infusion pump with a reservoir of at least 20 mL

Rotate infusion sites (ie, abdomen, thighs, hips, upper arms) from 1 infusion to the next

Do not infuse where skin is tender, bruised, red, or hard; avoid infusing into tattoos, scars, or stretch marks

Typical infusion time ~30 minutes (if using 2 infusion sites) or ~60 minutes (if using 1 infusion site)

Discard any unused portion

Self-administration

• After proper training in SC infusion, patient/caregiver may administer, if the healthcare provider deems appropriate

Missed dose

• Administer as soon as possible after missed dose
• Resume regular dosing schedule following administration of missed dose

Discontinuation

• Inform patients that they may develop hemolysis due to PNH when pegcetacoplan discontinued and that they need to be monitored by their healthcare professional for at least 8 weeks
• Instruct patients who discontinue pegcetacoplan to keep the Patient Safety Card with them for 2 months after the last dose, owing to increased risk of serious infection that persists for several weeks

Storage

Refrigerate at 2-8ºC (36-46ºF) in original carton to protect from light

Keep out of reach of children