Empaveli

Pegcetacoplan

• Brand(s): Empaveli
• Dosage Form/Strength: 1080 mg/20 mL vial Injection
• Effective date: May 15, 2024

Initial requests:

For the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in patients meeting ALL the following criteria;

1. 18 years of age or older; AND
2. Has had an inadequate response (Note 1) to at least one C5 complement inhibitor therapy (i.e. eculizumab, ravulizumab) used at a stable dose for at least 3 months OR has experienced an intolerance to a C5 complement inhibitor (Note 2); AND
3. Prior to the initiation of C5 complement inhibitor treatment (or if the patient has not had an adequate trial of C5 complement therapy and is initiating pegcetacoplan due to adverse reactions to a C5 complement inhibitor therapy), the patient meets the following criteria to confirm the diagnosis of PNH at initial presentation before the use of complement inhibitors;
   a. Patient has documentation (provide a copy of the reports) of BOTH of the following confirmatory results:
   • Flow cytometry/ Fluorescent aerolysin (FLAER) exam with clone count (i.e. granulocyte or monocyte) equal to or greater than 10%
   • Lactate dehydrogenase (LDH) greater than 1.5 upper limit of normal (ULN)
   AND
   b. AT LEAST ONE of the following clinical features:
   • Has experienced a thrombotic or embolic event which required the institution of therapeutic anticoagulant therapy.
   • Has a minimum transfusion requirement of 4 units of red blood cells in the previous 12 months.
   • Has chronic or recurrent anemia where causes other than hemolysis have been excluded and demonstrated by more than one measure of hemoglobin less than or equal to 70 g/L OR more than one measure of hemoglobin less than or equal to 100 g/L with concurrent symptoms of anemia.
   • Has pulmonary insufficiency: Debilitating shortness of breath and/or chest pain resulting in limitation of normal activity (New York Heart Association Class III) and/or established diagnosis of pulmonary arterial hypertension, where causes other than PNH have been excluded.
   • Has renal insufficiency: History of renal insufficiency, demonstrated by an eGFR less than or equal to 60 mL/min/1.73 m²;, where causes other than PNH have been excluded.
   • Has smooth muscle spasm: Recurrent episodes of severe pain requiring hospitalization and/or narcotic analgesia, where causes other than PNH have been excluded;
   AND
4. Pegcetacoplan is prescribed by or in consultation with a hematologist;
   AND
5. Pegcetacoplan is not being used in combination with another complement inhibitors (e.g. eculizumab or ravulizumab) except in the first 4 weeks of treatment.

Notes:

1. An inadequate response is defined as documentation of persistent anemia with hemoglobin levels < 105>
2. Please ensure that the full details of the adverse effects and intolerances are provided on your request. If the adverse event experienced by the patient to the C5 inhibitor is not considered to be cross-sensitive within the C5 inhibitor class, then both funded C5 inhibitors must be trialed.
3. Prescribers should submit relevant bloodwork to support the diagnosis including CBC, transfusion records, bone marrow report, flow cytometry/FLAER exam report, LDH levels, and as possible, recent consult notes.
4. Prescribers should comply with the most current National Advisory Committee on Immunization (NACI) recommendations for meningococcal vaccination in patients with complement deficiencies to reduce the risk of serious infection. Appropriate vaccination for meningococcal disease should be administered at least 2 weeks prior to receiving the first dose of pegcetacoplan and if this is not possible, refer to the product monograph for mitigating instructions.
5. Funding will not be considered if the patient or treating physician fails to comply adequately with treatment or measures, including monitoring requirements, required to evaluate the effectiveness of the therapy with pegcetocoplan.

Renewal criteria:

Renewals will be considered in patients who demonstrate clinical improvement or disease stabilization of PNH compared to baseline clinical results and symptoms prior to the initiation and use of pegcetacoplan.
(Note that the baseline may be those results after C5 complement inhibitor treatment was deemed to be inadequate OR if a patient was deemed intolerant to C5 inhibitors, it may be the baseline PNH results before an adequate use of complement therapy.)

As part of the renewal of funding, confirmation of clone size (by flow cytometry) should be submitted with the request. Granulocyte and monocyte clone size should be included to compare against the baseline results.

Exclusion criteria (applies to both initials and renewals)

Patients meeting one or more of the following are not approved for funding under the Ontario drug benefit program:

1. Previously experienced treatment failure with pegcetacoplan administered for the treatment of PNH.
2. Pegcetacoplan will not be funded in combination with another complement inhibitor. Use of combination will only be permitted during the first 4 weeks during transitioning of treatment.
3. Small granulocyte clone size - the treatment of patients with a granulocyte clone size below 10% will not be eligible for treatment.
4. Aplastic anemia with two or more of the following: neutrophil count below 0.5 x 10⁹/L, platelet count below 20 x 10⁹/L, reticulocytes below 25 x 10⁹/L, or severe bone marrow hypocellularity.
5. Patients diagnosed with another life threatening or severe disease where the long term prognosis is unlikely to be influenced by therapy (e.g. acute myeloid leukemia or high-risk myelodysplastic syndrome).
6. The presence of another medical condition that might reasonably be expected to compromise a response to therapy.

Approved doses:
Please refer to the product monograph for pegcetacoplan for further details about administration of the subcutaneous infusion using a commercially available syringe system infusion pump.

1080 mg subcutaneous infusion twice weekly on Day 1 and Day 4 of each treatment week.

The dosing regimen may be changed to 1080 mg every third day (i.e. Day 1, Day 4, Day 7, Day 10, Day 13, and so forth) if a subject has a lactate dehydrogenase (LDH) level greater than 2 × the upper limit of normal (ULN) on twice weekly dosing.

In the event of a dose increase, monitor LDH twice weekly for at least 4 weeks.

Dosage for patients switching to Empaveli from C5 inhibitors:

For the first 4 weeks, pegcetacoplan is administered as twice weekly subcutaneous doses of 1080 mg in addition to the patient’s current dose of C5 inhibitor treatment to minimize the risk of hemolysis with abrupt treatment discontinuation.

After 4 weeks, the patient can discontinue C5 inhibitor while continuing on monotherapy with pegcetacoplan.

Approval duration of initials: 6 months

Approved dosing of renewals: 1 year