Efficacy of intravitreal pegcetacoplan in geographic atrophy: results from the DERBY and OAKS trials

Efficacy of intravitreal pegcetacoplan in geographic atrophy: results from the DERBY and OAKS trials

Jeffrey Heier, Charles Wykoff, Rishi Singh, Nathan Steinle, David Boyer, Jordi Monés, Giovanni Staurenghi, Frank G. Holz, Caleb Bliss, Pascal Deschatelets, Federico Grossi, Cedric Francois, Ramiro Ribeiro

30 September 2021

Retina Society 2021, Chicago, USA

Disclosures

• Dr. Heier is a consultant for 4DMT, Adverum, Aerie, Aerpio, Aldeyra, Allegro, Alzheon, Annexon, Apellis, Aprea, Asclepix, Aviceda, BVT, Dark Horse, DTx, Eloxx, Galimedix, Genentech, Graybug, Gyroscope, Iveric Bio, jCyte, Kanghong, LensGen, NGM, Novartis, Ocular Therapeutix, OcuTerra, Oxurion, Palatin, Regeneron, Regenxbio, Stealth, Thea, Version, Vinci, and Voyant.
• Dr. Heier receives research funding from: Apellis, Asclepix, Bayer, Genentech, Graybug, Gyroscope, Hemera, Iveric , Kanghong, Kodiak, NGM, Notal Vision, Novartis, Regeneron, Regenxbio, and Stealth.
• Studies funded by Apellis Pharmaceuticals

2

Introduction

LECTIN		CLASSICAL
Polysaccharides on microorganisms		Antigen-antibody complexes

Pegcetacoplan

C3 convertase

C3aC3b

C5

C5 convertase

C5a

ALTERNATIVE

Pathogen cell surfaces and nonspecific/spontaneous activation

C3 amplification loop

Activation

removal antigen uptake

C5b MAC Cell

C5b, C6, C7,
C8, C9	proliferation

• Dysregulation of the complement cascade has been implicated in GA pathogenesis
• All 3 complement pathways end in the central cleavage of C3
• Pegcetacoplan is a pegylated, highly-selective peptide that binds C3, preventing its cleavage
• Inhibition of C3 blocks steps in the complement cascade needed for opsonization, inflammation, and formation of MAC

Figure adapted from Ricklin D, et al. Immunol Rev 2016;274(1):33-58.
APC=antigen-presenting cell; GA=geographic atrophy; MAC=membrane attack complex.	3
Liao DS, et al. Ophthalmology 2020;127:186-95.

Introduction and objective

Phase 2 FILLY Results

Change from baseline in square root GA lesion size (mm)

baseline	(mm)	0.4
		20% (every other month) reduction Primary endpoint
		p=0.067 vs sham*	Month 12	20%
fromchange(±SE)mean	lesionGArootsquarein
0.3
		29% (monthly) reduction		29%
		p=0.008 vs sham*
		0.2
		0.1
LS		0
		Baseline	M2	M6	M12
		Sham (n=80, pooled)	PEOM (n=78)	PM (n=84)

*P<0.1 was the predefined threshold for statistical significance in FILLY.

• Phase 3 DERBY & OAKS objective: to assess the efficacy and safety of multiple intravitreal injections of pegcetacoplan in patients with GA secondary to AMD

AMD=age-related macular degeneration; GA=geographic atrophy; LS=least squares; M=Month; PEOM=pegcetacoplan every other month; PM =pegcetacoplan monthly; SE=standard error.	4
Liao DS, et al. Ophthalmology 2020;127:186-95.

Global phase 3 program: Design of studies

Patients with GA secondary to AMD

~600 patients at ~200 sites globally in 2 studies (1258 enrollees total)

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 endpoint at 12 months

Change in total area of GA lesions based on fundus autofluorescence

End of study at 24 months

Protocol study number, APL-2 303 (DERBY); NCT03525600

Protocol study number, APL-2 304 (OAKS); NCT03525613

AMD=age-related macular degeneration; EOM=every other month; GA=geographic atrophy.	5