Effects of Pegcetacoplan on Quality of Life in Patients with Paroxysmal Nocturnal Hemoglobinuria from the PEGASUS Phase 3 Trial Comparing ...
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Effects of Pegcetacoplan on Quality of Life in Patients with
Paroxysmal Nocturnal Hemoglobinuria from the PEGASUS
Phase 3 Trial Comparing Pegcetacoplan to Eculizumab
Alexander Röth, Britta Höchsmann, Morag Griffin, Carlos M. de
Castro, Jeffrey Szer, Kensuke Usuki, Juliette Soret, Mohamed
Hamdani, Temitayo Ajayi, Sujata P. Sarda, and Jens Panse
The following information is available for educational purposes only. The information is not to be
re-purposed or re-used in its current form or presentation for any personal or professional use.
Abstract #764
Affiliations
• Röth, A: Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
• Höchsmann, B: University of Ulm and Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross
Blood Transfusion Service and University Hospital Ulm, Institute of Transfusion Medicine, Ulm, Germany
• Griffin, M: Department of Haematology, St James University Hospital, Leeds, United Kingdom
• de Castro, CM: Duke University School of Medicine, Durham, NC, USA
• Szer, J: Department of Clinical Haematology, Peter MacCallum Cancer Centre & Royal Melbourne Hospital, Melbourne,
Australia
• Usuki, K: Department of Hematology, NNT Medical Center Tokyo, Tokyo, Japan
• Soret, J: Centre d’Investigations Cliniques, Hôspital Sain-Louis; Assistance Publique – Hôpitaux de Paris; Université de
Paris, Paris, France
• Hamdani, M; Ajayi, T; Sarda, SP: Apellis Pharmaceuticals, Inc., Waltham, MA, USA
• Panse, J: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, University Hospital RWTH
Aachen, Aachen, Germany
The following information is available for educational purposes only. The information is not to be
re-purposed or re-used in its current form or presentation for any personal or professional use.Disclosures
• Röth, A: reports Consultancy and Honoraria for Alexion Pharmaceuticals, Apellis Pharmaceuticals, Biocryst, Novartis, Roche and Sanofi
and Research Funding for Alexion and Roche
• Höchsmann, B: reports Consultancy and Honoraria for Alexion, Apellis Pharmaceuticals, Novartis and Roche and Research Funding for
Alexion
• Griffin, M: reports Honoraria and Other: Conference Support for Alexion Pharmaceuticals and Membership on an entity’s Board of
Directors or advisory committees for Biocryst
• de Castro, CM: reports Honoraria Alexion Pharmaceuticals, Apellis Pharmaceuticals, Biocryst, Novartis and Research Funding for Alexion
and Apellis Pharmaceuticals and Other: “Data monitoring committee” for Biocryst, and Other: “Steering committee” for Novartis
• Szer, J: reports Consultancy for Alexion Pharmaceuticals, Apellis Pharmaceuticals and Novartis, and Honoraria for Alexion
Pharmaceuticals, Novartis, Pfizer and Takeda, and Speakers Bureau for Alexion Pharmaceuticals, Novartis, Pfizer and Takeda, and
Membership on an entity’s Board of Directors or advisory committee for Alexion Pharmaceuticals
• Usuki, K: reports Research Funding for Alexion Pharmaceuticals, Apellis, Chugai and Novartis, and Speakers Bureau for Alexion
Pharmaceuticals and Novartis
• Soret, J: nothing to disclose
• Hamdani, M: reports Current Employment and Current equity holder in publicly-traded company for Apellis Pharmaceuticals
• Ajayi, T: reports Current Employment and Current equity holder in publicly-traded company for Apellis Pharmaceuticals
• Sarda, SP: reports Current Employment and Current equity holder in publicly-traded company for Apellis Pharmaceuticals
• Panse, J: reports Membership on an entity’s Board of Directors or advisory committee for Apellis Pharmaceuticals, BMS, Grunenthal,
MSD, F. Hoffman-La Roche, Amgen, Alexion, Boehringer Ingelheim, Novartis and Blueprint Medicines, and Consultancy for Apellis
Pharmaceuticals, BMS, Grunenthal, MSD, F. Hoffman-La Roche, Amgen and Blueprint Medicines, and Speakers Bureau for Alexion,
Boehringer Ingelheim, Novartis, Pfizer and Chugai
The following information is available for educational purposes only. The information is not to be
re-purposed or re-used in its current form or presentation for any personal or professional use.Paroxysmal Nocturnal Hemoglobinuria (PNH) is an acquired disease
characterized by complement-mediated intravascular and extravascular
hemolysis and thrombosis
• Hemolysis can lead to anemia with associated fatigue, dyspnea, and
the need for transfusions1-3
– C5 inhibitors such as eculizumab reduce IVH but not C3-mediated
EVH4
• Pegcetacoplan is an investigational C3 inhibitor that has the
potential to control both IVH and EVH in PNH5,6
– Ongoing phase 3 trial PEGASUS: Pegcetacoplan was superior to
eculizumab in the primary endpoint (change from baseline
hemoglobin)
Unmet need: Persistent low hemoglobin in patients receiving
eculizumab4 which impacts their quality of life7,8
80-96% PNH patients report persistent fatigue 7,8
17% PNH patients name their disease the reason why they were not
working or were working less7,8
23% PNH patients report having been hospitalized due to their symptoms 8
1. Parker C, et al. Blood. 2005;106(12):3699-3709. 2. Risitano AM, Rotoli B. Biologics. 2008;2(2):205-222. 3. Risitano AM, et al. Blood. 2009;113(17):4094-4100. 4. McKinley CE, et al. Blood. 2017;130(suppl 1):3471. 5. Mehdi D, et al. Molecular Immunology. 2017;89:115. 6. de
Castro, C, et al. Am J Hematol. 2020; 95: 1334– 1343. 7. Meyers G, et al. Blood 2007;110:11. Abstract 3683 8. Schrezenmeier H, et al. Haematologica. 2014;99(5):922-929.
The following information is available for educational purposes only. The information is not to be
re-purposed or re-used in its current form or presentation for any personal or professional use.The PEGASUS (Phase 3) trial evaluated the efficacy and safety of
pegcetacoplan in patients with prior eculizumab treatment
• Patients ≥18 years with PNH and hemoglobinThe majority of patients who received pegcetacoplan achieved a clinically
meaningful improvement in the FACIT-fatigue score
Patients who achieve a
clinically meaningful
improvement* in FACIT-
fatigue score by Week 16
Pegcetacoplan 73.0%
Eculizumab 0.0%
*3-point increase 1
Descriptive summary using all available data not censored for transfusion
Baselinea Week 2b Week 4b Week 6b Week 8b Week 12b Week 16b
Pegcetacoplan (n=41) 32.2 (11.4) 10.8 (1.3) 8.7 (1.5) 7.6 (1.6) 10.0 (1.4) 10.0 (1.3) 9.2 (1.6)
Eculizumab (n=38) 31.6 (12.5) 0.5 (1.4) -4.4 (1.9) -5.4 (2.3) -3.5 (2.1) -3.7 (2.3) -2.7 (2.8)
p-value -Pegcetacoplan treatment increased the total LASA score from baseline
over the 16-week period, while eculizumab treatment did not
Descriptive summary using all available data not censored for transfusion
Baselinea Week 2b Week 4b Week 6b Week 8b Week 12b Week 16b
Pegcetacoplan (n=40) 161.0 (68.0) 59.4 (8.6) 57.5 (9.5) 49.8 (9.0) 55.8 (9.0) 63.2 (8.9) 52.7 (8.9)
Eculizumab (n=38) 156.7 (61.3) 4.1 (9.1) -37.7 (9.9) -13.4 (9.3) -6.7 (9.3) -3.4 (9.1) -10.7 (9.1)
p-value -By Week 16, the pegcetacoplan group had improved more EORTC QLQ-
C30 functional and symptom scale characteristics than the eculizumab
group
Pegcetacoplan n=41 Eculizumab n=39
EORTC QLQ-C30:
Baselinea CFB at Week 16b Baselinea CFB at Week 16b
Global Health Status/QoL 56.30 (20.39) 15.91 (3.64) 56.53 (20.24) −2.71 (8.52)
Functional Scales
Physical functioning 71.38 (20.23) 16.92 (2.08) 72.11 (20.14) 4.06 (3.61) Higher score:
Role functioning 63.82 (29.56) 15.39 (3.93) 59.65 (33.92) −9.04 (6.95) a higher level of
Emotional functioning 72.36 (25.38) 7.98 (3.37) 69.59 (22.67) 3.86 (7.24) function
Cognitive functioning 76.02 (24.45) 5.76 (3.26) 75.23 (25.95) −3.80 (6.42)
Social functioning 69.51 (28.84) 15.08 (2.95) 64.86 (32.82) 3.82 (6.35)
Symptom Scales
Fatigue 49.59 (29.09) −22.93 (3.32) 50.29 (24.74) −2.18 (6.64)
Negative value:
Nausea and vomiting 3.66 (8.75) −0.34 (1.63) 5.26 (11.69) −0.33 (3.88)
improvement in
Pain 19.51 (26.85) −0.74 (4.32) 15.79 (25.10) 2.01 (7.84)
the symptom
Dyspnea 33.33 (27.90) −20.12 (3.49) 43.86 (32.05) −5.55 (7.02)
Insomnia 32.52 (34.55) −9.18 (3.96) 29.82 (29.80) −9.50 (7.09)
scales
Appetite loss 12.20 (17.88) −3.76 (3.36) 13.16 (23.94) 4.19 (7.01)
Constipation 11.38 (20.56) 2.98 (3.25) 10.81 (22.30) 1.19 (8.13) Arrows denote greater than
10-point increases or
Diarrhea 11.38 (23.11) 0.31 (3.71) 11.71 (21.11) 1.68 (8.20) decreases in CFB scores,
Financial difficulties 18.70 (26.93) −6.82 (3.85) 24.32 (37.39) 0.58 (6.30) which is indicative of a
clinically meaningful
a Descriptive summary using all available data not censored for transfusion, mean (SD)
change1,2
b MMRM model change from baseline to Week 16, MMRM model excludes post transfusion data for patients with transfusion, LS mean CFB (SE)
EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 Scale; LS, least squares 1. Osoba D. et al. J Clin Oncol. 1998;16(1):139-144.
2 King MT. Qual Life Res. 1996;5(6):555-567.
The following information is available for educational purposes only. The information is not to be
re-purposed or re-used in its current form or presentation for any personal or professional use.Pegcetacoplan increased the global health status QoL scores of patients
with PNH, as measured with the EORTC QLQ-C30, at all time points
investigated
Descriptive summary using all available data not censored for transfusion
Baselinea Week 2b Week 4b Week 6b Week 8b Week 12b Week 16b
Pegcetacoplan (n=41) 56.30 (20.4) 17.3 (2.7) 18.1 (3.2) 15.2 (2.9) 16.2 (2.8) 18.7 (2.7) 15.4 (3.0)
Eculizumab (n=38) 56.53 (20.2) 0.38 (2.9) -11.0 (3.4) -7.8 (3.1) -5.0 (2.9) -3.0 (2.8) -3.8 (3.1)
p-value -Conclusions
PNH symptoms are debilitating and significantly reduce the quality of life of patients
with PNH
Substantial clinically relevant improvements in QoL were consistently observed with
pegcetacoplan compared to eculizumab through Week 16
– Majority of patients achieve a clinically meaningful improvement in FACIT-fatigue score
– Only the pegcetacoplan group demonstrated increases in total LASA score and the EORTCQLQ-
C30 global health status QoL score
Pegcetacoplan evaluation for QoL measures is ongoing via a phase 3 randomized,
multicenter, open-label PRINCE trial in complement inhibitor–naive patients
For further investigations into pegcetacoplan and PNH, please visit the following presentations:
• PEGASUS 16 Week Encore (Abstract #2579) • PEGASUS Response Criteria (Abstract #2588)
• PEGASUS Subgroups (Abstract #1681) • PADDOCK/PALOMINO Trials (Abstract #753)
PRINCE (NCT04085601)
The following information is available for educational purposes only. The information is not to be
re-purposed or re-used in its current form or presentation for any personal or professional use.Acknowledgements
• Patients who participated in the PEGASUS trial
• Valuable contributions by institution staff and investigators who participated in this study
• Writing and editorial support was provided by Boston Strategic Partners Inc. (supported by
Apellis Pharmaceuticals, Inc.)
• This study was supported by Apellis Pharmaceuticals, Inc.
Abstract #764
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