Efficacy of intravitreal pegcetacoplan in geographic atrophy: 24-month results from the phase 3 OAKS and DERBY trials

Efficacy of intravitreal pegcetacoplan in geographic atrophy: 24-month results from the phase 3 OAKS and DERBY trials

Jeffrey Heier, Rishi Singh, Charles Wykoff, Nathan Steinle, David Boyer, Jordi Monés, Giovanni Staurenghi, Caleb Bliss, Mari Nakabayashi, Ramiro Ribeiro, David Lally, Ian Pearce, Robyn Guymer, Eleonora Lad, Frank G. Holz

November 2-5, 2022

Retina Society

Pasadena, CA, USA

Disclosures

• I have the following financial interests or relationships to disclose:

1. Consultant: 4DMT, Abpro, Adverum, Aerie, Affamed, Allegro, Allergan, Allgenesis, Annexon, Apellis Pharmaceuticals, Aprea, Asclepix, Aviceda, BVT, Chengdu Kanghong Biotechnology, DTx, Eloxx, Galimedix, Graybug, Gyroscope, Horizon Therapeutics, IVERIC Bio, Laboratoires Thea, Lensgen, NGM Biopharmaceuticals, Novartis, Ocular Therapeutix, Oriole, Oxurion, Palatin, Regeneron, REGENXBIO, Roche/Genentech, Santen, Scifluor, Stealth Biotherapeutics, Surrozen, Verseon, and Vinci

1. Stockholder: Apellis Pharmaceuticals

• 1. Research grants: Apellis Pharmaceuticals
• Studies funded by Apellis Pharmaceuticals

2

If approved, pegcetacoplan will be the first and only treatment for patients with GA

• Slows GA progression with both every-other-month and monthly dosing, with effects increasing over time
• Safety data collected in real world population of over 1,200 patients with nearly 12,000 injections studied for 2 years

3

Pegcetacoplan binds to C3 and C3b inhibiting the downstream effects of the complement pathway

Classical pathway

Lectin pathway

Alternative Pathway

C1q

C3(H2O)

MBL

MASPs

C1r/C1s

Factor B

Factor D

C4

C2

C4bC2b (C3 convertase)

C3bBb (C3 convertase)

Amplification

loop

C3

Inflammation

C3a

Pegcetacoplan

C3b

Opsonization

C3bBbC3b (C5 convertase)

C4bC2bC3b (C5 convertase)

C5

C5a

C5b

C5b C6

C9

Cell lysis

C7

C8

MAC

MAC=membrane attack complex; MBL=mannose-binding lectin; MASP=MBL-associated serine protease
1. Kolev M et al. Nat Rev Immunol 2014;14:811 -20; 2. Holers VM. Annu Rev Immunol 2014;32:433-59; 3. Dunkelberger JR, Song WC. Cell Res 2010;20:34 -50;
4. Strunz T et al. Sci Rep 2020;10:1584; 5. Anderson DH et al. Am J Ophthalmol 2002;134:411-31; 6. Boyer DS et al. Retina 2017;37:819 -35.	4

Design of the Phase 3 OAKS and DERBY studies

Patients with GA secondary to AMD

1258 patients at 232 sites in the combined studies

Double-masked					Randomized 2:2:1:1
			Pegcetacoplan		Pegcetacoplan		Sham		Sham
			15 mg/0.1 mL
				15 mg/0.1 mL EOM		monthly		EOM
			monthly

Primary analysis:

MMRM methodology

Fixed effects:

• Treatment*, time, treatment x time interaction
• Baseline GA lesion and fellow eye CNV area strata
• Baseline GA lesion strata × time interaction

*Sham monthly and EOM were pooled for analysis

Primary endpoint at 12 months

Change in total area of GA lesions based on fundus autofluorescence

Prespecified secondary endpoints at 24 months

•	BCVAa, LL-BCVA	•	FRI Index scorea
•	Reading speeda	• Microperimetry (OAKS only)a - MAIA device
•	NEI VFQ-25	•	Lesion growth

GALE 3-yearopen-label extension study

OAKS, DERBY, GALE CT.gov identifiers: NCT03525613, NCT03525600, NCT04770545, respectively. aKey secondary endpoints. AMD=age-related macular degeneration;

BCVA=best-corrected visual acuity; CNV=choroidal neovascularization; EOM=every other month; FRI=Functional Reading Independence; GA=geographic atrophy; LL=low 5 luminance; MAIA=macular integrity assessment; MMRM=mixed-effectsmodel for repeated measures ; NEI-VFQ=National Eye Institute Visual Function Questionnaire.