Complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria (PNH) may experience greater hemoglobin stabilization and lactate dehydrogenase (LDH) reduction with pegcetacoplan treatment than with only supportive care, according to a study published in Blood Advances.

The phase 3, randomized, multicenter, open-label, controlled PRINCE study was aimed at evaluating the efficacy and safety of pegcetacoplan in comparison to supportive care only, including blood transfusions, corticosteroids, anticoagulants, and supplements such as iron, folate, and vitamin B12 for the treatment of PNH in complement inhibitor-naïve patients.

The study comprised a 4-week screening period and a 26-week randomized controlled period. A group of 35 patients with PNH self-administered 1080 mg of pegcetacoplan subcutaneously twice per week, while the group of 18 control patients continued to receive standard supportive care.

The researchers monitored hemoglobin stabilization (defined as the avoidance of >1g/dL decrease in hemoglobin levels without transfusions) from baseline through week 26 and LDH change at week 26 as coprimary endpoints.

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According to the results, pegcetacoplan was superior to supportive care for hemoglobin stabilization and change from baseline in LDH. The majority of patients who received pegcetacoplan (85.7%) reached hemoglobin stabilization at week 26, as opposed to no patients (0%) from the control group. Moreover, treatment with pegcetacoplan resulted in mean LDH levels at or below 226 U/L (ULN) by week 4 that were maintained through week 26.

There were no reports of serious pegcetacoplan-related adverse events and the medication was well-tolerated, researchers wrote.

“Mean hemoglobin increased 3.4 g/dL from baseline to a mean of 12.8 g/dL at week 26. The high rates of improved and stabilized hemoglobin allowed nearly all (91%) patients who received pegcetacoplan to avoid transfusions throughout the 26-week study,” Wong and colleagues wrote.

“It is also noteworthy that patients who escaped from the control group because of acute hemolysis (ie, hemoglobin decrease of ≥2 g/dL from baseline) had rapid improvement in hemoglobin levels after initiating pegcetacoplan”.

This study was conducted across 22 centers in Hong Kong, Malaysia, the Philippines, Singapore, Thailand, Colombia, Mexico, and Peru. At these locations, complement inhibitors such as eculizumab and ravulizumab were not approved or widely available and patients with PNH received only supportive care.

Pegcetacoplan is the first C3-targeted therapy approved for the treatment of PNH in the United States, Australia, and the European Union.


Wong SMR , Navarro-Cabrera JR, Comia NS, et al. Pegcetacoplan controls hemolysis in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuriaBlood Adv. Published online February 27, 2023. doi:10.1182/bloodadvances.2022009129