Efficacy and Safety of Pegcetacoplan Treatment in Complement-Inhibitor Naïve Patients with Paroxysmal Nocturnal Hemoglobinuria: Results from the Phase 3 PRINCE Study

Efficacy and Safety of Pegcetacoplan Treatment in Complement-

Inhibitor Naïve Patients with Paroxysmal Nocturnal

Hemoglobinuria: Results from the Phase 3 PRINCE Study

Raymond S Wong, MBChB, MD, Juan Ramon Navarro, MD, Narcisa Sonia Comia, MD, Yeow Tee

Goh, MBBS, Henry Idrobo, MD, Daolada Kongkabpan, MD, David Gomez-Almaguer,MD,

Mohammed Al-Adhami, PhD, Temitayo Ajayi, MD, Paulo Alvarenga, MD, PhD, Pascal Deschatelets,

PhD, Cedric Francois, MD, PhD, Federico Grossi, MD, PhD, and Teresita Dumagay, MD

Abstract #606

Affiliations

David Gomez-Almaguer,MD:Department of Haematology, University Hospital Dr. José Eleuterio González, Monterrey, Mexico

Raymond S Wong, MBChB, MD:Sir YK Pao Centre for Cancer & Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Hong Kong

Juan Ramon Navarro, MD:Department of Hematology, Edgardo Rebagliati Hospital, Lima, Peru

Narcisa Sonia Comia, MD:Research Center, 6th Floor Medical Arts Building 3, Mary Mediatrix Medical Center, Lipa, Philippines

Yeow Tee Goh, MBBS:Department of Haematology, Singapore General Hospital, Singapore

Henry Idrobo, MD:Department of Haematology, Julian Coronel Medical Center, Cali, Colombia

Daolada Kongkabpan, MD:Department of Medicine, Songklanagarind Hospital, Songkhla

Mohammed Al-Adhami,PhD:Apellis Pharmaceuticals, Waltham, MA, United States

Temitayo Ajayi, MD:Apellis Pharmaceuticals, Waltham, MA, United States

Paulo Alvarenga, MD, PhD:Apellis Pharmaceuticals, Waltham, MA, United States

Pascal Deschatelets, PhD:Apellis Pharmaceuticals, Waltham, MA, United States

Cedric Francois, MD, PhD:Apellis Pharmaceuticals, Waltham, MA, United States

Federico Grossi, MD, PhD:Apellis Pharmaceuticals, Waltham, MA, United States

Teresita Dumagay, MD:Department of Cellular Therapeutics, Makati Medical Centre, Makati City, Philippines

Disclosures

David Gomez-Almaguer,MD:Reports consultancy, honoraria, and speakers bureau with Teva, Amgen, Janssen, Takeda, BMS, Roche, Abvvie.

Raymond S Wong, MBChB, MD:Reports consultancy, honoraria, research funding, and speakers bureau with Alexion Pharmaceuticals, Inc. and F. Hoffmann-La Roche Ltd. Dr. Wong also reports research funding and speakers bureau with Apellis Pharmaceuticals, Inc.

Juan Ramon Navarro, MD:Nothing to disclose

Narcisa Sonia Comia, MD:Nothing to disclose

Yeow Tee Goh, MBBS:Nothing to disclose

Henry Idrobo, MD:Nothing to disclose

Daolada Kongkabpan, MD:Nothing to disclose

Mohammed Al-Adhami,PhD:Reports current employment with Apellis Pharmaceuticals, Inc.

Temitayo Ajayi, MD:Reports current employment and current equity holder in the publicly traded-company Apellis Pharmaceuticals, Inc.

Paulo Alvarenga, MD, PhD:Reports consultancy with Apellis Pharmaceuticals, Inc.

Pascal Deschatelets, PhD:Reports current employment and current equity holder in the publicly traded-company Apellis Pharmaceuticals, Inc.

Cedric Francois, MD, PhD: Reports current employment and current equity holder in the publicly traded-company Apellis Pharmaceuticals, Inc.

Federico Grossi, MD, PhD:Reports current employment and current equity holder in the publicly traded-company Apellis Pharmaceuticals, Inc.

Teresita Dumagay, MD:Nothing to disclose

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a Rare and Potentially Life-Threatening Disease Characterized by Complement-Mediated Hemolysis and Thrombosis

• PNH results in debilitating complement-mediated hemolysis and an increased risk of thrombosis1
• Uncontrolled complement activation leads to intravascular hemolysis (IVH), mediated by the membrane attack complex and extravascular hemolysis (EVH), mediated by accumulation of C3 fragments, such as C3b, at the red blood cell surface2
• • IVH is associated with increased LDH and reticulocytosis
  • EVH is associated with bilirubinemia and reticulocytosis, without increases in LDH
• Pegcetacoplan, which binds C3 as well as C3b and inhibits C3 cleavage, was approved by the U.S. FDA in May 2021 to treat adults with PNH by controlling IVH and
  EVH

Pegcetacoplan

C3

C3 convertase

C3b opsonin

Abbreviations: EVH, extravascular hemolysis; FDA, Food and Drug Administration; IVH, intravascular hemolysis; LDH, lactate dehydrogenase; MAC, membrane attack complex; PNH, Paroxysmal Nocturnal Hemoglobinuria; U.S., United States

References: 1. DeZern AE, et al. Eur J Haematol. 2013;90(1):16-24. 2. Mastellos DC, et al. Expert Rev Hematol. 2014; 7(5):583-598.

PRINCE: A Phase 3 Study Evaluating the Efficacy and Safety of Pegcetacoplan Compared to Standard of Care in Complement-Inhibitor Naïve Patients with PNH

Up to 4 weeks

Screening

Complement-Inhibitor Naïve Patients with PNH

No complement-inhibitor

treatment (i.e., eculizumab,

ravulizumab) within 3 months

prior to screening1

53 Patients

Baseline:

Average of measurements prior to randomization

26 weeks

Randomized Controlled Period

Pegcetacoplan

(1080 mg subcutaneously twice weekly)

35 Patients

Standard of Care

(Excluding complement-inhibitors

eculizumab, ravulizumab)

18 Patients

Day 1, 2:1 Randomization:

Stratified by number of RBC transfusions within the 12 months prior to screening (<4, ≥4)

Standard of Care Escape

Option to escape to

pegcetacoplan therapy if

hemoglobin decreased by

≥2 g/dL from baseline

11 Patients

Week 26 Analysis of Co-

Primary and Secondary

Endpoints

		Study Design
Population		Patients ≥18 years of age with PNH
		• No complement-inhibitor (i.e., eculizumab, ravulizumab) treatment within 3 months prior to screeninga
Key Eligibility Criteria		• Hb levels below the LLN (males: ≤13.6 g/dL; females: ≤12.0 g/dL)
		• LDH levels ≥1.5 times the ULN (1.5x ULN; ≥339 U/L)
		Endpoints
Co-Primary Endpoints		• Hb stabilization (avoidance of a >1 g/dL decrease in Hb levels in the absence of transfusions through Week 26)
	• Change from baseline in LDH levels at Week 26
		• Change from baseline in Hb levels at Week 26
Selected Secondary		• Transfusion avoidance (defined as the proportion of patients who did not require a transfusion or discontinue/escape
Endpoints		through Week 26)
		• Incidence and severity of adverse events (including study deaths) through Week 26

Abbreviations: Hb, hemoglobin; LDH, lactate dehydrogenase; LLN, lower limit of normal; PNH; paroxysmal nocturnal hemoglobinuria; ULN, upper limit of normal

• All patients screened in PRINCE had never received a complement inhibitor at any point