Pegcetacoplan

There are no data available for the use of pegcetacoplan in patients with end-stage renal disease (ESRD) requiring haemodialysis.

Pegcetacoplan is a PEGylated medicinal product. The potential long-term effects of PEG accumulation in the kidneys, the choroid plexus of the brain, and other organs are unknown. Regular laboratory testing of renal function is recommended.

There are no or limited amount of data from the use of pegcetacoplan in pregnant women. Studies in animals have shown reproductive toxicity.

Pegcetacoplan is not recommended during pregnancy and in women of childbearing potential not using contraception.

It is unknown whether pegcetacoplan is excreted in human milk. The potential for absorption and harm to the breastfed infant is unknown. Animal data suggest a low excretion (less than 1%, not pharmacologically significant) of pegcetacoplan in monkey milk. It is unlikely that a breastfed infant would have clinically relevant exposure.

It is recommended to discontinue breast-feeding during pegcetacoplan treatment.

Women of childbearing potential

It is recommended that women of childbearing potential use effective contraception methods to prevent pregnancy during treatment with pegcetacoplan and for at least 8 weeks after the last dose of pegcetacoplan. For women planning to become pregnant, the use of pegcetacoplan may be considered following an assessment of the risks and benefits (see Pregnancy).

Fertility

No animal or human data on the effect of pegcetacoplan on fertility are available. In toxicity studies, there were no microscopic abnormalities in male or female reproductive organs in monkeys.

Pegcetacoplan has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most commonly reported adverse reactions in patients treated with pegcetacoplan were injection site reactions: injection site erythema, injection site pruritus, injection site swelling, injection site pain. Other adverse reactions reported in more than 10% of patients during clinical studies were upper respiratory tract infection, abdominal pain, diarrhoea, headache, fatigue, and pyrexia. The most commonly reported serious adverse reactions were haemolysis and thrombocytopenia.

Tabulated list of adverse reactions

The table below gives the adverse reactions observed from the clinical studies with pegcetacoplan in patients with PNH. Adverse reactions are listed by MedDRA system organ class (SOC) and frequency, using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100) or rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), and not known (cannot be estimated from available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Adverse reactions:

The ADRs listed in the table are from clinical studies APL2-302, Study 202, Study 204, and Study CP0514.
¹ Upper respiratory tract infection includes preferred terms of Upper respiratory tract infection, Nasopharyngitis, Pharyngitis, Rhinitis, Sinusitis, Tonsillitis, Tonsillitis bacterial, and Viral pharyngitis.
² Haemolysis includes preferred terms of Haemolysis, Haemolytic anaemia, and Intravascular haemolysis.
³ Thrombocytopenia includes the preferred terms of Platelet count decreased and Thrombocytopenia.
⁴ Abdominal pain includes preferred terms of Abdominal pain, Abdominal pain upper, Abdominal pain lower, and Abdominal discomfort.
⁵ Fatigue includes preferred terms of Fatigue and Asthenia.
⁶ Pyrexia includes preferred terms of Pyrexia and Body temperature increased.

Description of selected adverse reactions

Infections

Based on its mechanism of action, the use of pegcetacoplan may potentially increase the risk of infections, particularly infections caused by encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis types A, C, W, Y, and B, and Haemophilus influenzae. No infection caused by encapsulated bacteria was reported during Study APL2-302. The most frequent infections in patients treated with pegcetacoplan during the run-in and randomised controlled periods (RCP) of Study APL-302 were upper respiratory tract infections (11 cases, 13.8%). Most infections reported in patients treated with pegcetacoplan during the run-in and RCP were non-serious, and predominantly mild in intensity. Four serious infections were reported in Study APL2-302: one bacterial infection, one viral upper respiratory tract infection, and one gastroenteritis during the RCP, and one sepsis during the run-in period in a patient with history of renal transplant. Of these, two were severe in intensity (gastroenteritis and sepsis). None of these events led to discontinuation of pegcetacoplan.

Haemolysis

Six cases of haemolysis were reported during the run-in (1 case) and RCP (5 cases) of Study APL2-302 in patients treated with pegcetacoplan. Three cases were serious in nature and severe in intensity. One of the serious episodes of haemolysis resulted in pegcetacoplan discontinuation. The remaining events were non-serious in nature and moderate in intensity; of these, 2 led to discontinuation of pegcetacoplan.

Immunogenicity

Anti-drug antibody (ADA) incidence (seroconverted ADA or boosted ADA from pre-existing level) were low, and when present, had no noticeable impact on the PK/PD, efficacy, or safety profile of pegcetacoplan. In Study APL2-302 up to Week 16, 2 out of 80 patients developed anti-pegcetacoplan peptide antibodies. Both patients also tested positive for neutralizing antibody (NAb). NAb response had no apparent impact on PK or clinical efficacy. Two out of 80 patients developed anti-PEG antibody incidence; one was seroconversion and one was treatment-boosted which was transient.