Phase 3 BEACON study delivers positive topline results for tarcocimab in patients with retinal vein occlusion

Kodiak Sciences announced that its BEACON Phase 3 study (NCT04592419) 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.

The company noted in a news release that 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.

Mark Barakat, MD, director of the Retinal Research Institute at Retinal Consultants of Arizona and a BEACON study investigator, pointed out in a news release that RVO is a disease with a heavy treatment burden, and all approved anti-VEGF treatments for RVO are labeled for monthly dosing.

“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,” he said in the release. “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."

According to the company, the BEACON study is a randomly assigned, 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 randomly assigned 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 randomly assigened 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 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.”

Victor Perlroth, MD, Kodiak's CEO, the company’s 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," he said.

Moreover, Perlroth noted that 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,” Perlroth said. “All the studies are fully enrolled and expected to read out topline data within the next 12 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.

About the BEACON Study

The Phase 3 BEACON study is a global, multi-center, randomly assigned study designed to evaluate the durability, efficacy and safety of tarcocimab tedromer in patients with treatment-naïve macular edema due to retinal vein occlusion, including both branch and central subtypes. Patients are randomized 1:1 to receive tarcocimab 5 mg or aflibercept 2 mg. In the first six months, patients receiving tarcocimab are treated with a proactive, fixed regimen which includes two monthly loading doses followed by treatment every 8 weeks, and patients receiving aflibercept are treated monthly as per its label. In the second 6 months, patients in both groups will receive treatment on an individualized basis per protocol-specified criteria.

Following this, patients can continue to receive tarcocimab tedromer for an additional 6 months on an individualized basis. The study completed enrollment of 568 patients worldwide in the fourth quarter of 2021 and met its primary efficacy endpoint at six months. Results from the BEACON study are intended to serve as the basis for the potential approval of tarcocimab in RVO.