Why carry out this study?
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Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening hematologic disease for which complement component 5 (C5) inhibitor standard-of-care treatments provide inadequate disease control in some patients and require regular clinic visits for intravenous treatment administration |
Pegcetacoplan is approved by the United States Food and Drug Administration for the treatment of adults with PNH and by the European Medicines Agency for the treatment of adults with PNH plus anemia despite receiving C5-targeted therapy for ≥ 3 months. Pegcetacoplan demonstrated durable clinical benefit and a favorable safety profile in the phase 3 PEGASUS trial (NCT03500549). Patients with PNH receiving pegcetacoplan via self-administered subcutaneous (SC) injections in PEGASUS who experienced injection site reactions (ISRs) experienced mild ones. To better understand the long-term tolerance of pegcetacoplan SC injections, the incidence and severity of ISRs with an additional 48 weeks of pegcetacoplan treatment in the PEGASUS cohort of the open-label extension (OLE) of Study 307 (307 OLE; NCT03531255) were investigated |
What was learned from this study?
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With longer-term pegcetacoplan treatment in the PEGASUS cohort of the 307 OLE, most patients reported ISRs with a maximum severity of mild, consistent with the observations in PEGASUS. The percentage of patients reporting ISRs declined from PEGASUS through the 307 OLE, and compliance remained high, suggesting that ISRs are not a barrier to continued pegcetacoplan treatment in patients with PNH |
Patient education about proper self-administration techniques may help mitigate the impact of ISRs on the patient experience and enable patients to continue to obtain long-term disease control with pegcetacoplan treatment |
Introduction
Methods
Study Design and Patients
Safety Analysis
Injection Training and ISR Collection
Data Analysis
Results
Patients
Demographic and disease characteristics | PEGASUS cohort of the 307 OLE (n = 64)a |
---|---|
Age, mean (SD), years | 48.5 (15.2) |
Sex, n (%) | |
Female | 39 (60.9) |
Male | 25 (39.1) |
Race, n (%) | |
White | 40 (62.5) |
Asian | 11 (17.2) |
Black | 2 (3.1) |
Other | 1 (1.6) |
Not reported | 10 (15.6) |
BMI, mean (SD), kg/m2 | n = 54 26.2 (4.5) |
Time since PNH diagnosis, mean (SD), years | 10.6 (8.4) |
Hemoglobin level, mean (SD), g/dlb | 11.5 (1.8) |
Absolute reticulocyte count, mean (SD), 109 cells/lc | n = 60 80.3 (33.1) |
LDH level, mean (SD), U/ld | n = 63 213.6 (126.9) |
Indirect bilirubin level, mean (SD), µmol/le | n = 60 10.5 (6.1) |
Total FACIT-Fatigue Scale score, mean (SD) | n = 63 41.1 (10.0) |
ISRs
Study period | PEGASUS9 | PEGASUS cohort of the 307 OLE (week 48)a | |||
---|---|---|---|---|---|
Run-in period | RCP | OLP | |||
Therapy | Pegcetacoplan + eculizumabb (n = 80) | Pegcetacoplan (n = 41) | Eculizumab (n = 39) | Pegcetacoplan-to-pegcetacoplan and eculizumab-to-pegcetacoplan (n = 77) | Pegcetacoplan (n = 64) |
Any ISR TEAE, n (%)c | 47 (58.8) | 15 (36.6) | 1 (2.6) | 20 (26.0) | 9 (14.1) |
Mild | 44 (55.0) | 14 (34.1) | 1 (2.6) | 18 (23.4) | 7 (10.9) |
Moderate | 3 (3.8) | 1 (2.4) | 0 (0.0) | 2 (2.6) | 2 (3.1) |
Severe | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
PT, n (%)d | |||||
Injection site erythema | 33 (41.3) | 7 (17.1) | 0 | 9 (11.7) | 4 (6.3) |
Injection site pruritus | 12 (15.0) | 1 (2.4) | 0 | 5 (6.5) | 2 (3.1) |
Injection site swelling | 10 (12.5) | 4 (9.8) | 0 | 1 (1.3) | 0 |
ISR | 8 (10.0) | 4 (9.8) | 0 | 2 (2.6) | 2 (3.1) |
Injection site pain | 6 (7.5) | 1 (2.4) | 0 | 4 (5.2) | 1 (1.6) |
Injection site induration | 5 (6.3) | 3 (7.3) | 0 | 5 (6.5) | 4 (6.3) |
Infusion site reaction | 2 (2.5) | 0 | 0 | 0 | 1 (1.6) |
Injection site rash | 2 (2.5) | 0 | 0 | 0 | 0 |
Injection site bruising | 1 (1.3) | 2 (4.9) | 0 | 3 (3.9) | 1 (1.6) |
Infusion site erythema | 1 (1.3) | 0 | 0 | 1 (1.3) | 0 |
Administration site discoloration | 1 (1.3) | 0 | 0 | 0 | 0 |
Infusion site bruising | 1 (1.3) | 0 | 0 | 0 | 0 |
Infusion site induration | 1 (1.3) | 0 | 0 | 0 | 0 |
Injection site discoloration | 1 (1.3) | 0 | 0 | 0 | 0 |
Injection site mass | 1 (1.3) | 0 | 0 | 0 | 0 |
Vaccination site erythema | 1 (1.3) | 0 | 0 | 0 | 0 |
Vaccination site pain | 1 (1.3) | 0 | 1 (2.6) | 0 | 2 (3.1) |
Vaccination site swelling | 1 (1.3) | 0 | 0 | 0 | 0 |
Infusion site swelling | 0 | 1 (2.4) | 0 | 1 (1.3) | 1 (1.6) |
Infusion site urticaria | 0 | 1 (2.4) | 0 | 0 | 0 |
Injection site scar | 0 | 0 | 0 | 0 | 1 (1.6) |
Injection site hemorrhage | 0 | 0 | 0 | 3 (3.9) | 1 (1.6) |
Injection site hematoma | 0 | 0 | 0 | 1 (1.3) | 0 |
Study period | PEGASUS | PEGASUS cohort of the 307 OLE (week 48)b | |||
---|---|---|---|---|---|
Run-in period | RCP | OLP | |||
Therapy | Pegcetacoplan + eculizumabc (n = 80) | Pegcetacoplan (n = 41) | Eculizumab (n = 39) | Pegcetacoplan-to-pegcetacoplan and eculizumab-to-pegcetacoplan (n = 77) | Pegcetacoplan (n = 64) |
PT, n (%)d | |||||
Injection site erythema | 25 (31.3) | 6 (14.6) | 0 | 9 (11.7) | 3 (4.7) |
Injection site swelling | 10 (12.5) | 4 (9.8) | 0 | 1 (1.3) | 1 (1.6) |
Injection site pruritus | 10 (12.5) | 1 (2.4) | 0 | 4 (5.2) | 2 (3.1) |
ISR | 8 (10.0) | 4 (9.8) | 0 | 2 (2.6) | 0 |
Injection site induration | 5 (6.3) | 3 (7.3) | 0 | 5 (6.5) | 3 (4.7) |
Injection site pain | 4 (5.0) | 1 (2.4) | 0 | 3 (3.9) | 1 (1.6) |
Infusion site swelling | 0 | 0 | 0 | 0 | 1 (1.6) |
Study period | PEGASUS | PEGASUS cohort of the 307 OLE (week 48)a | ||
---|---|---|---|---|
RCP | OLP | |||
Therapy | Pegcetacoplan (n = 41) | Pegcetacoplan (n = 64) | Pegcetacoplan-to-pegcetacoplan and eculizumab-to-pegcetacoplan (n = 77) | Pegcetacoplan (n = 64) |
PTb, n (e)c | ||||
Injection site erythema | 7 (56.8) | 0 | 9 (20.1) | 4 (6.5) |
ISR | 4 (32.5) | 0 | 2 (4.5) | 2 (3.1) |
Injection site swelling | 4 (32.5) | 0 | 1 (2.2) | 1 (1.5) |
Injection site induration | 3 (24.4) | 0 | 5 (11.2) | 4 (6.5) |
Injection site bruising | 2 (16.2) | 0 | 3 (6.7) | 1 (1.5) |
Injection site pruritus | 1 (8.1) | 0 | 5 (11.2) | 2 (3.1) |
Injection site pain | 1 (8.1) | 0 | 4 (8.9) | 1 (1.6) |
Infusion site swelling | 1 (8.1) | 0 | 1 (2.2) | 0 |
Infusion site urticaria | 1 (8.1) | 0 | 0 | 0 |
Infusion site hemorrhage | 0 | 0 | 3 (6.7) | 1 (1.6) |
Infusion site erythema | 0 | 0 | 1 (2.2) | 0 |
Infusion site pain | 0 | 0 | 1 (2.2) | 0 |
Injection site hematoma | 0 | 0 | 1 (2.2) | 0 |
Injection site scar | 0 | 0 | 0 | 1 (1.5) |
Vaccination site pain | 0 | 2 (16.6) | 0 | 2 (3.1) |