PEGCETACOPLAN INJ,SOLN
Clinical Criteria Summary
Document 431: MON Pegcetacoplan EMPAVELI Monograph April 2023a
Indication
- Paroxysmal nocturnal hemoglobinuria (PNH)
Dosage & Administration
- 1080 mg by subcutaneous infusion twice weekly
- Infusion duration: 30 minutes if using two infusion sides, or 60 minutes if using one infusion site
- Patient can self-administer; obtained via specialty pharmacy
REMS Requirements
- Prescribers must enroll in the Empaveli REMS program
- Providers must counsel patients on the risk of serious infection and provide REMS educational materials
- Patients must be vaccinated against encapsulated bacteria (Streptococcus pneumoniae, Neisseria meningitidis, Hemophilus influenzae)
- Pharmacies must be REMS registered; specialty pharmacy dispensing is recommended due to daily data file submission requirements
Contraindications
- Hypersensitivity to pegcetacoplan or any component of the formulation
- Patients not currently vaccinated against encapsulated bacteria (unless risks of delaying treatment outweigh infection risk)
- Unresolved infection caused by encapsulated bacteria
Warnings & Precautions
- Boxed Warning: Risk of serious infections caused by encapsulated bacteria (Streptococcus pneumoniae, Neisseria meningitidis types A, C, W, Y, and B, Haemophilus influenzae type B)
- Vaccination against encapsulated bacteria should occur at least 2 weeks before the first dose; adhere to ACIP recommendations for complement deficiencies
- Live vaccines should not be administered to patients on pegcetacoplan
- Consider restarting pegcetacoplan if signs of hemolysis occur after discontinuation
- Pregnancy: Insufficient data on drug-associated risks; animal studies showed increased stillbirths and abortions; weigh risks of untreated PNH against potential fetal/maternal risks
- Lactation: Avoid breastfeeding during treatment and up to 40 days after the last dose
Place in Therapy / Clinical Guidance
- Complement C3 inhibitor indicated for PNH
- May be reasonable to consider in patients refractory to a complement C5 inhibitor, including those experiencing breakthrough hemolysis or who remain anemic after at least three months of complement C5 inhibitor therapy
- More frequent administration schedule (twice weekly subcutaneous) compared to complement C5 inhibitors (every 8 weeks or every 2 weeks intravenous)
Document 566: Pegcetacoplan SYFOVRE Criteria
Exclusion Criteria
- Geographic atrophy that is secondary to a condition other than age-related macular degeneration
- Ocular or periocular infections
- Active intraocular inflammation
Inclusion Criteria
- Provider is a VA or VA Community Care ophthalmologist
- Diagnosis of geographic atrophy secondary to age-related macular degeneration
Pregnancy and Reproductive Safety
- Pregnancy should be excluded prior to receiving pegcetacoplan
- Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 40 days after stopping treatment
Monitoring and Management
- Patients should be monitored for signs of neovascular AMD due to increased rates of neovascular (wet) AMD or choroidal neovascularization associated with use in clinical trials
- If anti-Vascular Endothelial Growth Factor (anti-VEGF) is required, it should be given separately from pegcetacoplan administration
Document 570: MON Pegcetacoplan SYFOVRE Monograph
Indication
- • Treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD)
- • Use restricted specifically to GA secondary to AMD in the absence of contraindications
Contraindications
- • Ocular or periocular infection
- • Active intraocular inflammation
Dosing & Administration
- • Intravitreal injection of 15 mg (0.1 mL of 150 mg/mL solution) to each affected eye
- • Administered once every 25 to 60 days
Monitoring & Precautions
- • Monitor patients for signs of neovascular AMD
- • If anti-VEGF therapy is required, administer separately from pegcetacoplan administration
- • Discontinue use of injection kits containing 19-gauge filter needles per manufacturer recommendation due to post-marketing reports of retinal vasculitis
Special Populations
- • Women of childbearing potential: Use effective contraception during treatment and for 40 days after the last dose
Document 634: Pegcetacoplan Iptacopan Danicopan for Paroxysmal Nocturnal Hemoglobinuria Criteria
Criteria for Paroxysmal Nocturnal Hemoglobinuria (PNH) - Alternative Pathway Complement Inhibitors (Danicopan, Iptacopan, Pegcetacoplan)
- Exclusion Criteria
- Active infection with Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, or Streptococcus pneumoniae
- Inclusion Criteria
- Must be prescribed by a REMS registered VA or VA Community Care hematologist, oncologist, immunologist or genetic specialist
- Laboratory-confirmed diagnosis of Paroxysmal Nocturnal Hemoglobinuria (PNH), as evidenced by detectable GPI-deficient hematopoietic clones (Type III PNH red blood cells (RBC)) via Flow Cytometry
- Evidence of clinically significant hemolysis (e.g., Hemoglobin <10g/dL) despite 6 months of stable therapy with anti-C5 inhibitor (e.g., ravulizumab or eculizumab)
- Complete or update vaccination for encapsulated bacteria, including Streptococcus pneumoniae and Neisseria meningitidis at least 2 weeks prior to the first dose of therapy according to current Advisory Committee on Immunization Practices (ACIP)
- Note: All criteria listed above apply collectively to Danicopan, Iptacopan, and Pegcetacoplan for the treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH).