Pegcetacoplan bests SoC for PNH in PRINCE update

Treatment with pegcetacoplan improves the quality of life (QoL) of patients with paroxysmal nocturnal haemoglobinuria (PNH) who were naïve to complement inhibitor therapy, according to the PRINCE study update presented at EHA 2022. This comes with the added benefit of disease control.

Pegcetacoplan-treated patients had ≥10 points improvement from baseline in their EORTC QLQ-C30* Global Health Status/Quality of Life scores, reaching a mean of 83.3 and exceeding the general population norm of 66.1. [EHA 2022, abstract S303]

This benefit was reached by week 4 and sustained through week 26. Additionally, patients on pegcetacoplan achieved clinically meaningful improvements in physical, role, emotional, and social functioning scores on the EORTC QLQ-C30. These increases occurred early, at scores near or above the general population norms, and were sustained through week 26. Most increases were ≥10 points from baseline, which were not seen in the standard of care (SoC) arm.

Unmet needs in PNH

“PNH is a rare, acquired, and potentially life-threatening haematological disorder,” lead author Dr David Gómez-Almaguer from the Hospital Universitario ‘Dr José Eleuterio González’ in Monterrey, Mexico told EHA attendees. “Patients living with PNH suffer from disease-associated symptoms, which can impact their overall QoL. These include haemolysis, smooth muscle dystonia, renal impairment, anaemia, thrombosis, and fatigue.”

Patients with PNH often use C5 inhibitors to control their symptoms. C5 inhibition controls intravascular haemolysis in untreated PNH but not extravascular haemolysis (EVH). Because of persistent EVH, up to 72 percent of patients treated with eculizumab, a C5 inhibitor, remain anaemic. Up to 36 percent require at least one transfusion a year. [ASH 2021, abstract 606]

Pegcetacoplan was developed out of a need for an inhibitor of complement-mediated hemolysis further upstream of C5. “It is USFDA/EMA-approved for PNH patients who remain anaemic for at least 3 months on a C5 inhibitor,” said Gómez-Almaguer.

Evidence for pegcetacoplan

In a phase III open-label, controlled trial, pegcetacoplan was superior to eculizumab in improving haemoglobin and clinical and haematologic outcomes in PNH. This comes with the benefit of haemolysis control, including intravascular and extravascular haemolysis. [N Engl J Med 2021;384:1028-1037]

In the current phase III PRINCE study, 53 complement inhibitor-naïve adults with PNH were randomized 2:1 to 26 weeks of treatment with pegcetacoplan 1,080 mg, given twice weekly by subcutaneous injection (n=35), or SoC, which excluded complement inhibitors (n=18).

Patients in the SoC arm, whose haemoglobin decreased by ≥2 g/dL from baseline, had the option to switch to the pegcetacoplan arm. Ultimately, 11 patients did. At baseline, all patients had a haemoglobin level below the lower limit of normal and lactate dehydrogenase (LDH) levels of 1.5 times beyond the upper limit of normal.

The co-primary endpoints of the study were stabilization of haemoglobin, defined as the avoidance of a >1 g/dL drop from baseline, and change in LDH from baseline to 26 weeks. Secondary endpoints included the EORTC QLQ-C30, Linear Analog Scale Assessment (LASA), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score.

Previous findings presented at ASH 2021 showed pegcetacoplan was superior to SoC with respect to the co-primary endpoints. At week 26, 45.7 percent of patients taking pegcetacoplan achieved normal haemoglobin; 65.7 percent had a normal LDH vs 0 percent with SoC.

Gómez-Almaguer presented the QoL data at EHA 2022. Fatigue Symptom score on the EORTC QLQ-C30 improved with pegcetacoplan, and so did the FACIT-Fatigue score to 45.3, near the population norm of 44.0, at week 26.

The mean total LASA score also improved from 186.5 points at baseline to 241.0 points at week 26 (a higher score indicates better QOL) in the pegcetacoplan group but decreased in the SoC group.

Adverse events occurred in 28.3 percent of patients treated with pegcetacoplan, none of them serious. There were no cases of acute haemolysis in either arm.

“Patients with PNH who were naïve to complement inhibitor therapy exhibited meaningful QoL improvements through 26 weeks of pegcetacoplan treatment,” recapped Gómez-Almaguer. “The safety profile was favourable and consistent with previous clinical trials.”