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Pegcetacoplan indication extended to first-line for adults with PNH in Europe

Pegcetacoplan (brand name Aspaveli) has been approved by the European Commission for use as a first-line treatment in adults with paroxysmal nocturnal haemoglobinuria (PNH) who have haemolytic anaemia.

The complement 3 (C3) inhibitor is already approved in Europe for the treatment of adults with PNH who are anaemic after treatment with a C5 inhibitor for at least three months.

Several cross-sectional patient surveys, including one looking at patients in France, Germany and the UK, have shown that despite improvements with C5 inhibitor treatment, up to 86% of people with PNH treated with C5 inhibitors remain anaemic.

This indication expansion makes pegcetacoplan the first C3 inhibitor approved for first-line treatment of PNH in Europe.

Safety and efficacy of pegcetacoplan

The pegcetacoplan indication extension is based on data from the phase 3, randomised, multi-centre, open-label, controlled PRINCE study, which aimed to evaluate the efficacy and safety of pegcetacoplan versus a control group who received supportive care only.

Supportive care included blood transfusions, corticosteroids and supplements such as iron, folate and vitamin B12 and excluded complement inhibitors.

The study enrolled 53 adult patients with PNH who had not been treated with any complement inhibitor within three months prior to enrolment and who had haemoglobin levels less than the lower limit of normal and lactate dehydrogenase levels ≥1.5 times the upper limit of normal.

Patients were randomly assigned and stratified based on their number of transfusions (<4 or ≥4) 12 months before screening.

Patients received pegcetacoplan 1080 mg subcutaneously twice weekly (n=35) or continued supportive care (n=18) for 26 weeks.

Coprimary endpoints were haemoglobin stabilisation (avoidance of >1-g/dL decrease in haemoglobin levels without transfusions) from baseline through Week 26 and lactate dehydrogenase (LDH) change at week 26.

Pegcetacoplan was found to be superior to control for haemoglobin stabilisation (pegcetacoplan, 85.7%; control, 0; difference, 73.1%; 95% confidence interval [CI], 57.2-89.0; P < .0001) and change from baseline in LDH (least square mean change: pegcetacoplan, −1870.5 U/L; control, −400.1 U/L; difference, −1470.4 U/L; 95% CI, −2113.4 to −827.3; P < .0001).

Pegcetacoplan was well tolerated, with no serious pegcetacoplan-related adverse events and no newly observed safety signals.

The authors concluded that ‘pegcetacoplan rapidly and significantly stabilised haemoglobin and reduced LDH in complement inhibitor–naive patients and had a favourable safety profile’.

This ‘may help expand the treatment population’, they added.

In 2021, the indication for the monoclonal antibody ravulizumab was extended to children with PNH who weigh 10kg and above.

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