In a new study, pegcetacoplan showed superiority to eculizumab in treatment of low hemoglobin in patients with paroxysmal nocturnal hemoglobinuria (PNH). The study results were presented at the British Society of Haematology 61st Annual Scientific Meeting by Morag Griffin, MBChB, FRCPath, of St James University Hospital in Leeds, UK, and colleagues.

The study was the phase 3 PEGASUS trial (ClinicalTrials.gov Identifier: NCT03500549), in which patients with PNH were randomized to receive either pegcetacoplan monotherapy (41 patients) or eculizumab (39 patients) for 16 weeks. This randomized, controlled period had followed a 4 week run-in period in which patients received pegcetacoplan with eculizumab. The primary study endpoint was the change in hemoglobin level from the start of the run-in period (baseline) to week 16, and efficacy analyses evaluated the intent-to-treat population.

Primary endpoint analysis indicated superiority for pegcetacoplan over eculizumab in improvement of hemoglobin at week 16; the adjusted treatment difference was 3.84 g/dL (P <.0001). At baseline, patients in both groups had a mean hemoglobin level of 8.7 g/dL. At week 16, patients in the pegcetacoplan population had a mean hemoglobin level of 11.5 g/dL, while the eculizumab population had a mean hemoglobin level of 8.6 g/dL.


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Freedom from red blood cell transfusions was seen in 85.4% of patients in the pegcetacoplan arm and in 15.4% of patients in the eculizumab arm, with an adjusted risk difference of 62.5% (95% CI, 48.3%-76.8%), which reflected noninferiority for pegcetacoplan. Noninferiority was also seen with the change in absolute reticulocyte count, but an analysis of lactate dehydrogenase (LDH) levels could not assess noninferiority of either treatment because of large standard errors.

At week 16, there was a normalization of hemoglobin in 34.1% of patients in the pegcetacoplan group, while reportedly no patients in the eculizumab group achieved this. Normalization of reticulocyte count was reported for 78.0% of patients in the pegcetacoplan group and 2.6% of the eculizumab group.

Treatment-emergent adverse events (TEAEs) were reported to occur with a similar incidence in each group. Any TEAE occurred in 87.8% of patients in the pegcetacoplan group and in 87.2% of the eculizumab group. Serious TEAEs occurred in 17.1% of patients in the pegcetacoplan group and in 15.4% of patients in the eculizumab group. In the randomized, controlled trial period, there were no patient deaths reported.

The study investigators considered pegcetacoplan to demonstrate superiority over eculizumab in improvement of week-16 hemoglobin levels in this trial. Additionally, in this trial pegcetacoplan showed noninferiority to eculizumab for key secondary endpoints of freedom from transfusions and change in absolute reticulocyte count. The investigators suggested there is potential for pegcetacoplan to be a new treatment option for PNH.

Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Griffin M, Hillmen P, Szer J, et al. Results of the Pegasus phase 3 randomized trial demonstrating superiority of the C3 inhibitor, pegcetacoplan, compared to eculizumab in patients with paroxysmal nocturnal hemoglobinuria. Poster presented at: the British Society of Haematology 61st Annual Scientific Meeting; April 25-28, 2021; virtual.