Author: Arshad Khanani
Co-authors: Jason S Ehrlich, Daniel Janer, Pablo Velazquez-Martin, Rezi Zawadzki, Victor Perlroth
AbstractPurpose: Vascular endothelial growth factor (VEGF) suppression therapy is the first-line treatment for macular edema (ME) secondary to retinal vein occlusion(RVO). Substantial functional and anatomic improvements can be achievedusing currently approved dosing regimens of anti-VEGFs. However, increased treatment burden continues to prevent good outcomes from being consistently achieved in the clinical setting.KSI-301 is an antibody biopolymer conjugate (ABC) designed to providesafe and longer-lasting intraocular VEGF suppression.The objective of the BEACON study is to demonstrate that KSI-301 is non-inferior to aflibercept while providing a clinically meaningful reduction intreatment burden for patients with ME secondary to RVO.
Setting: A Phase 3 prospective, randomized, double-masked, two-arm, multi-centernon-inferiority study evaluating the efficacy and safety of repeated intravitreal dosing of KSI-301 5 mg vs aflibercept 2 mg in participants with visual impairment due to treatment-naÔve macular edema secondary to RVO.
Methods: Treatment-naÔve patients with ME secondary to branch or central RVOwere randomized 1:1 into two treatment arms: aflibercept 2 mg dosedmonthly or KSI-301 5 mg dosed every eight weeks (Q8W) after two initialmonthly doses. The primary efficacy endpoint is the mean change in best corrected visual acuity (BCVA) at Week 24. Secondary endpoints at Week 24 include change from baseline in retinal thickness measured by optical coherence tomography (OCT) central subfield thickness (CST), the proportions of patients gaining or losing ?10 or ?15 ETDRS letters from baseline, and the incidence of ocular and non-ocular adverse events.Starting at Week 24 through the end of the study, patients in both treatmentarms are evaluated monthly and treated according to protocol defined disease activity criteria.
Results: 134 sites across the United States, Europe and Israel randomized 568 patients (279 females, 49.1%) into the study with a mean age of 65.3 years. At baseline, mean BCVA was 60.4 letters with 32% of patientshaving a Snellen equivalent of 20/40 or better; mean baseline CST was 577.4 um. Results for the primary endpoint will be presented for the first time at the meeting.
Conclusions: Patients with treatment naÔve ME secondary to RVO can achieve substantial improvements in function and anatomy when treated with monthly dosing of currently available anti-VEGF therapies. However, this high treatment burden imposed on patients, caregivers, clinicians and the healthcare system prevents a significant proportion of patients fromachieving and maintaining these outcomes in the clinical setting. The ABC platform leverages the unique biophysical properties of branched phosphorylcholine biopolymers to maintain effective therapeutic levels of a biologic, such as an anti-VEGF antibody, for longer periods of time inside the eye, for this reason KSI-301 has the potential to address this unmet medical need. Data on the Week 24 primary efficacy outcomes will bepresented for the first time at the EURETINA meeting.
Financial Disclosure: Research grant from Kodiak Sciences. Consultant for Kodiak Sciences.