Tuesday, August 09, 2022
Kodiak Sciences Inc., announced that its BEACON Phase 3 study of tarcocimab tedromer (KSI-301; tarcocimab), its novel antibody biopolymer conjugate, met the primary endpoint of non-inferior change from baseline in visual acuity at week 24 compared to aflibercept in patients with macular edema due to retinal vein occlusion. Tarcocimab also demonstrated robust anatomic responses and a favorable safety profile. After two initial monthly loading doses, tarcocimab was dosed every two months compared to consistent monthly dosing for aflibercept.
"RVO is a disease with a heavy treatment burden, and all approved anti-VEGF treatments for RVO are labeled for monthly dosing," said Mark Barakat, MD, Director of the Retinal Research Institute at Retinal Consultants of Arizona and a BEACON study investigator. "BEACON is the first study to successfully test a doubling of the treatment interval for anti-VEGF dosing in a pivotal trial in RVO patients. Testing only two loading doses and an extended, fixed dosing interval for all patients rather than assigning a subset of patients to extended dosing based on disease activity assessment is an especially high bar because eyes of patients with RVO can have the highest VEGF levels across retinal vascular diseases. It's wonderful news for patients that the study was successful: it showed that treatment with tarcocimab results in non-inferior vision outcomes, while meaningfully reducing the treatment burden compared to monthly aflibercept."
The BEACON study is a randomized, double-masked, multicenter, active comparator-controlled Phase 3 clinical trial in treatment naïve patients with vision loss and macular edema due to retinal vein occlusion, including both branch (BRVO) and central (CRVO) subtypes. This condition occurs when a branch or central draining vein of the retina becomes blocked, for example due to chronic hypertension, and the retina becomes swollen as a result. The study randomized 568 participants (438 BRVO, 130 CRVO) from 11 countries 1:1 into two treatment arms: tarcocimab tedromer 5 mg on a fixed every-8-week dosing regimen following 2 monthly loading doses and aflibercept 2 mg on a fixed every 4-week dosing regimen per its label.
The primary efficacy endpoint of the study was change in best-corrected visual acuity (BCVA) score, a measure of the best vision a person can achieve when reading letters on an eye chart, from baseline at week 24. In the first 24 weeks of the study, patients randomized to tarcocimab received a total of 4 doses compared with 6 doses received by patients randomized to aflibercept.
The non-inferiority margin for the comparison to aflibercept at week 24 was established at 4.5 eye chart letters based on pretrial regulatory feedback and precedent. Under the study's prespecified statistical analysis plan and hierarchical testing strategy for control of type 1 error, non-inferiority of tarcocimab to aflibercept was first demonstrated in patients with branch RVO, with a statistically significant p-value of 0.0004, and then also demonstrated with a statistically significant p-value of 0.0243 in the overall RVO population (branch and central types combined). Tarcocimab tedromer was safe and well tolerated in the study, with no new safety signals identified. A low rate of intraocular inflammation was observed in both groups (1.4% vs 0.4% for tarcocimab and aflibercept, respectively) with no vasculitis or retinal arterial occlusion events reported in any patient.
"The positive results of the BEACON study show that tarcocimab can rapidly, robustly and safely improve vision and retinal anatomy in patients with macular edema due to RVO while substantially reducing the number of eye injections," said Jason Ehrlich, MD, PhD, Chief Medical Officer and Chief Development Officer of Kodiak. "We're hopeful that BEACON also bodes well for our ongoing Phase 3 GLEAM and GLIMMER studies of tarcocimab in diabetic macular edema, because both RVO and DME are diseases of the inner retina in which elevated VEGF levels in the vitreous and retina result in retinal vascular leakage and retinal swelling. We thank the patients who participated in BEACON and the many clinicians, site staff and Kodiak team members who worked together on this study and the broad tarcocimab clinical program."
"Our regulatory strategy is designed to have two successful studies in one indication and then individual studies in additional indications. Looking across our development program for tarcocimab, our paired Phase 3 GLEAM and GLIMMER studies in DME, if successful, are designed to serve as the primary basis for a licensing application and potential regulatory approval of tarcocimab," said Victor Perlroth, MD, Kodiak's Chief Executive Officer. "BEACON serves as the single pivotal study to support approval in macular edema following RVO. Our Phase 3 DAYLIGHT study and our Phase 3 GLOW study, if successful, would contribute data to support approvals in wet AMD and Non-Proliferative Diabetic Retinopathy (NPDR), respectively. All the studies are fully enrolled and expected to read out topline data within the next twelve months and, if successful, we would plan to file a single Biologics License Application (BLA) with the data across the program. As we learn more from the remaining Phase 3 studies, we look forward to continuing to work with the FDA and global health authorities to bring this medicine to patients."
Full primary results from the BEACON study are expected to be presented by BEACON Study Investigators at upcoming ophthalmology congresses in September 2022.