Two investigational therapies developed by Kodiak Sciences met their primary endpoints in the phase 3 DAYBREAK trial for neovascular age-related macular degeneration (nAMD), with one demonstrating the potential to maintain visual gains with dosing intervals of up to 6 months. The findings provide additional evidence for the durability of tarcocimab tedromer as the company prepares a regulatory submission.
Charles C. Wykoff, MD, PhD, FASRS, of Retina Consultants of Texas, presented the first-year results at Retina Subspecialty Day during the American Academy of Ophthalmology (AAO) 2026 meeting in New Orleans. Dr. Wykoff, a consultant to Kodiak Sciences, reported findings for tarcocimab tedromer (KSI-301 or Zenkuda), a long-acting anti-VEGF antibody–biopolymer conjugate, and tabirafusp-ted (KSI-501), a bispecific antibody–biopolymer conjugate targeting VEGF and interleukin-6 (IL-6).
The randomized, double-masked DAYBREAK trial enrolled 667 treatment-naïve patients with nAMD. Each investigational agent was evaluated independently against aflibercept 2 mg (Eylea; Regeneron) administered every 8 weeks following 3 monthly loading doses. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline, averaged across weeks 40, 44, and 48. The trial will continue through week 96 to evaluate longer-term efficacy, durability, and safety.
Dr. Wykoff noted that a distinguishing feature of the trial was the use of an artificial intelligence algorithm to detect intraretinal and subretinal fluid within the central 3 mm of the macula to guide retreatment. Unlike other pivotal nAMD trials, DAYBREAK did not require a specified increase in central subfield thickness or loss of visual acuity. “The goal here was to approximate how retina specialists actually determine disease activity using a ‘treat-to-dry’ and ‘maintain-dry’ approach,” he explained.
At the primary endpoint, mean BCVA gains were 7.2 ETDRS letters with tarcocimab and 7.6 ETDRS letters with aflibercept, meeting the noninferiority endpoint (P=.0007). Dr. Wykoff reported that 54% of tarcocimab-treated patients had achieved a 24-week dosing interval, while another 29% were receiving treatment every 12, 16, or 20 weeks (Figure 1). The median number of injections after the loading phase was 1 with tarcocimab vs 5 with aflibercept.
Tabirafusp-ted 5 mg, administered every 8 weeks with additional monthly treatment as indicated, also met its primary endpoint (Figure 2). Mean BCVA gains at week 48 were 6.3 letters vs 7.6 letters with aflibercept (P=.0036). The agent also demonstrated noninferiority in retinal drying, with central subfield thickness reductions of 131 μm and 138 μm, respectively (P<.0001).
No intraocular inflammation occurred in the tarcocimab or aflibercept groups, compared with 1 case in the tabirafusp-ted group. No cases of endophthalmitis or occlusive retinal vasculitis were reported.
For tabirafusp-ted, Dr. Wykoff said the future is “to continue to examine which patients may benefit from combined anti-VEGF plus anti-IL-6 treatment.” Planned post hoc analyses and the ongoing phase 3 ALTO trial in diabetic macular edema will further evaluate the agent.
With DAYBREAK, tarcocimab has now completed “5 positive phase 3 trials: 2 in wet AMD, 2 in diabetic retinopathy, and 1 in retinal vein occlusion,” noted Dr. Wykoff. Based on that, Kodiak plans to submit a multi-indication biologics license application to the US Food and Drug Administration later this year, he said. RP