P794: evaluation of pegcetacoplan in paroxysmal nocturnal hemoglobinuria patients with aplastic anemia in the prince study

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: Patients with paroxysmal nocturnal hemoglobinuria (PNH) in the setting of aplastic anemia (AA) often benefit less from current C5 inhibitors than other PNH patients. Pegcetacoplan (PEG) is an FDA/EMA approved C3 complement inhibitor that provides broad hemolysis control in PNH patients. In the phase 3 PRINCE trial (NCT04085601), PEG showed superiority over control treatment (supportive care without complement inhibitors) regarding the proportion of patients achieving hemoglobin (Hb) stabilization and reduction of mean lactate dehydrogenase (LDH) levels (Wong SR, et al. Blood 2021; suppl 1 Vol 138). Treatment with PEG also led to significant improvements in reticulocyte count, Hb, transfusion avoidance, normalization of hematologic values, fatigue, and quality of life compared with supportive care. Aims: Evaluate efficacy and safety of PEG treatment in the randomized, open-label, multicenter, PRINCE study, focusing on patients with and without a history of AA. Methods: 53 adult complement-inhibitor naïve patients with PNH (Hb < lower limit of normal and LDH ≥1.5x upper limit of normal) were randomized 2:1 to PEG (n=35) or the control arm (n=18) through 26 weeks. During the randomized controlled period (RCP) there was the option to escape from the control arm to PEG therapy (n=11) if Hb decreased by ≥2 g/dL from baseline or a qualifying thromboembolic event secondary to PNH occurred. Outcomes in the subpopulation of patients with and without AA were presented at Week 6 (W6) when the steady state of PEG is reached (Aspaveli SmPC) and before patients escaped the control group. Results: 5 of 35 patients in the PEG group and 5 of 18 patients in the control arm had a history of AA. 3 and 8 patients with and without AA from the control arm escaped to PEG treatment. At baseline, hematologic parameters were broadly comparable between AA and non-AA patients. Improvements in Hb, LDH, reticulocytes, transfusion avoidance and fatigue were achieved in PEG patients and outcomes were comparable between the AA and non-AA subgroups (Table 1). PEG improved Hb levels in AA patients, with a mean change from baseline (CFB) of 2.97 g/dL compared to control (mean CFB 0.32 g/dL) at W6, consistent with non-AA patients (mean CFB 2.66 g/dL and -0.07 g/dL for PEG and control arms, respectively). PEG-treated patients demonstrated greater reductions in mean LDH levels from baseline to W6 compared to control patients in both AA (mean CFB: PEG, -1792.4 U/L; control, 55.9 U/L), and non-AA patients (mean CFB: PEG, -2012.7 U/L; control, 14.6 U/L), and mean LDH levels below the upper limit of normal were achieved at W6 in both PEG-treated patient groups. Furthermore, reticulocyte count was improved in PEG-treated AA-patients to a similar extent as in non-AA patients at W6. Transfusion avoidance throughout the RCP was achieved in all AA patients and 90% of non-AA patients treated with PEG. Clinically meaningful improvements in fatigue were also achieved for both AA and non-AA PEG-treated patients. The PEG safety profile in the RCP was comparable between the AA and non-AA subgroups and consistent with the overall population. The most common adverse events (AE) in AA patients on PEG treatment were injection site reactions. Serious AEs were seen in 12.5% of PEG-treated AA patients, similarly to PEG-treated non-AA patients (13.2%). Summary/Conclusion: While the subgroup of patients with AA was small, PEG improved all efficacy parameters at W6, demonstrating comparable outcomes to patients with no history of AA. The PEG safety profile was consistent with previously reported data.Keywords: Aplastic anemia, Clinical outcome, Paroxysmal nocturnal hemoglobinuria (PNH), Complement