Successful switch from pegcetacoplan to iptacopan after repeated severe breakthrough hemolysis events - case report

A subset of paroxysmal nocturnal hemoglobinuria (PNH) patients develops clinically relevant extravascular hemolysis when treated with complement C5 inhibitors. These patients may benefit proximal complement inhibitors such as pegcetacoplan, danicopan or iptacopan. No studies comparing these substances are available. Breakthrough hemolysis (BTH) - defined by exacerbation of intravascular hemolysis despite complement inhibition - can be severe especially in patients treated with proximal complement inhibitors.

We report on a PNH patient who had suffered repeated episodes of severe BTH with acute renal failure during 1 year of treatment with pegcetacoplan. The patient was switched to iptacopan and followed also for 1 year.

After switching to iptacopan, no further BTH occurred for the duration of 12 months follow up. The patient maintained stable hemoglobin and reticulocyte counts as well as lactate dehydrogenase (LDH) levels within the normal range.

Despite dose escalation of pegcetacoplan, BTH recurred in our patient. Therefore, an alternative therapy was warranted. During iptacopan therapy - chosen due to patient preference -no further BTH occurred. However, more data from a larger number of patients are needed.

A switch to iptacopan may be an option for pegcetacoplan treated patients who experience repeated BTH in spite of dose escalation.