A third medication, pegcetacoplan, was recently added to the Pharmaceutical Benefits Scheme (PBS) to treat paroxysmal nocturnal haemoglobinuria (PNH). This joins the complement C5 inhibitors, eculizumab and ravulizumab, which are also PBS listed for this rare condition.

Pegcetacoplan is indicated for use in patients who have an inadequate response to, or are intolerant of, a complement C5 inhibitor. Inhibitors of C5 reduce haemolysis caused by membrane attack complex (MAC), but haemolysis can still occur due to C3b opsonisation. Studies suggest that polymorphic variations in complement genes may also lead to a poor response to C5 inhibitors in some people. Pegcetacoplan targets upstream sections of the complement cascade (C3 and its activation fragment, C3b) to affect a broader regulation of the complement cascade.

Pegcetacoplan is administered as a twice-weekly subcutaneous infusion. One of the more serious adverse effects is an increased risk of infections. Complement plays a critical role in the immune response to various pathogens, although it appears to be most important against encapsulated bacteria. Therefore, patients receiving pegcetacoplan are at increased risk of infections caused by pathogens such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. As these infections can be serious, all patients should be vaccinated against these bacteria at least two weeks before starting pegcetacoplan therapy. If the risk of delaying therapy outweighs the risk of infection, pegcetacoplan may be initiated less than two weeks after vaccination, but patients must receive appropriate prophylactic antibiotics until two weeks after vaccination. The Australian Immunisation Handbook can be referred to for current vaccination advice.


  1. Empaveli® (Pegcetacoplan) Australian approved product information. Sydney: Swedish Orphan Biovitrum. Approved March 2022.
  2. Rondelli T, Risitano AM, de Latour RP, Sica M, Peruzzi B, Ricci P, et al. Polymorphism of the complement receptor 1 gene correlates with the hematologic response to eculizumab in patients with paroxysmal nocturnal hemoglobinuria. Haematologica 2014; 99(2): 262-6.
  3. Toh ZQ, Higgins RA, Mazarakis N, Abbott E, Nathanielsz J, Balloch A, et al. Evaluating functional immunity following encapsulated bacterial infection and vaccination. Vaccines (Basel). 2021; 9(6): 677.

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