EMPAVELI

What it is

Empaveli is a solution for injection containing pegcetacoplan, supplied as a clear, colourless to slightly yellowish aqueous solution administered by subcutaneous infusion. Pegcetacoplan binds to complement protein C3 and its activation fragment C3b with high affinity, thereby regulating the cleavage of C3 and the generation of downstream effectors of complement activation.

Approved indications

— Treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH). — Treatment of adults and adolescents aged 12 to 17 years with C3 glomerulopathy (C3G) or primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN).

Dosing overview

For adult patients with PNH, Empaveli is administered twice weekly as a 1,080 mg subcutaneous infusion on Day 1 and Day 4 of each treatment week. The dosing regimen may be changed to 1,080 mg every third day if a subject has a lactate dehydrogenase (LDH) level greater than 2 × upper limit of normal (ULN). For adolescent patients with C3G or primary IC-MPGN, dosing is based on body weight. Adult patients with C3G or primary IC-MPGN receive 1,080 mg twice weekly, whilst adolescents weighing 50 kg or more also receive 1,080 mg twice weekly with a loading regimen, adolescents weighing 35 to less than 50 kg receive a loading schedule of 648 mg then 810 mg followed by maintenance at 810 mg twice weekly, and adolescents weighing 30 to less than 35 kg receive loading at 540 mg twice, followed by maintenance at 648 mg twice weekly.

Key safety warnings

Use of Empaveli may predispose individuals to serious infections, especially those caused by encapsulated bacteria, such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B, which may become rapidly life-threatening or fatal if not recognised and treated early. All patients must be vaccinated against these bacteria according to current local guidelines at least 2 weeks prior to receiving Empaveli, unless the risk of delaying therapy with Empaveli outweighs the risk of developing an infection. Patients who initiate treatment with Empaveli less than 2 weeks after vaccination must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Hypersensitivity reactions have been reported. If a severe hypersensitivity reaction (including anaphylaxis) occurs, discontinue infusion with Empaveli immediately and institute appropriate treatment. If patients with PNH discontinue treatment with Empaveli, they should be closely monitored for signs and symptoms of serious intravascular haemolysis, identified by elevated LDH levels along with sudden decrease in PNH clone size or haemoglobin, or reappearance of symptoms such as fatigue, haemoglobinuria, abdominal pain, shortness of breath, major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction. If discontinuation of Empaveli is necessary, an alternate therapy should be considered because PNH is life-threatening if untreated.

Contraindications

Empaveli is contraindicated in patients with hypersensitivity to pegcetacoplan or to any of the excipients. Empaveli is contraindicated in patients with unresolved infection caused by encapsulated bacteria including Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae.

PBS listing

Empaveli is listed on the PBS as a solution for subcutaneous infusion at a strength of 1,080 mg in 20 mL under 8 items, with authority required restrictions, at an ex-manufacturer price of A$4343.86.

Regulatory history

Empaveli (pegcetacoplan 1080 mg/20 mL injection solution) was first listed on the ARTG on 2022-02-03. The Australian Public Assessment Report approval date was 2022-01-28 for the indication of treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH) who have an inadequate response to, or are intolerant of, a C5 inhibitor. The PBAC initially provided a not recommended outcome in March 2022, followed by a recommended outcome in July 2022 for paroxysmal nocturnal haemoglobinuria in adults with inadequate clinical response to complement component 5 (C5) inhibitor treatment. In May 2025, the PBAC recommended Empaveli for treatment of adults with paroxysmal nocturnal haemoglobinuria (PNH) who are either treatment-naïve to complement 5 (C5) inhibitors or currently treated with a C5 inhibitor. Empaveli is subject to additional monitoring in Australia due to approval of an extension of indications.