DAYBREAK: Tarcocimab, tabirafusp-ted noninferior to aflibercept in wet AMD

Two investigational intravitreal agents from Kodiak Sciences met the primary end point of the phase 3 DAYBREAK trial in treatment-naive neovascular age-related macular degeneration (AMD). Tarcocimab tedromer (proposed brand name Zenkuda; formerly KSI-301) and the bispecific tabirafusp alfa tedromer (tabirafusp-ted; KSI-501) each achieved best-corrected visual acuity (BCVA) gains noninferior to aflibercept at 1 year, according to topline results the company released September 28, 2026.¹

The company reported that 54% of tarcocimab-treated patients were on a 24-week dosing interval at year 1. Retreatment criteria in the trial required a new injection for any detectable fluid on optical coherence tomography (OCT).¹ It is the first positive wet AMD readout for tarcocimab on an extended, individualized regimen. In 2022, a phase 2b/3 trial that tested fixed extended intervals missed its primary end point.²

Trial design and results

DAYBREAK (NCT06556368) is a noninferiority trial with parallel tarcocimab and tabirafusp-ted arms and an aflibercept comparator arm.^1,3

• Tarcocimab arm: After 4 monthly loading doses, patients received individualized, as-needed dosing every 4 to 24 weeks. Retreatment followed a treat-to-dry approach that used retinal fluid as the disease activity marker, rather than a combination of central subfield thickness and vision loss.
• Tabirafusp-ted arm: After 4 monthly loading doses, patients received fixed dosing every 8 weeks, with additional as-needed doses up to monthly under the same fluid criteria.
• Aflibercept arm: Patients were dosed per label. The release does not specify which regimen.
• Primary end point: Mean change in BCVA from baseline to the average of weeks 40, 44, and 48.¹

Tarcocimab met the primary end point (P = .0007). Tabirafusp-ted also met the primary end point (P = .0036) and a key anatomic secondary end point (P < .0001).¹ The company said tarcocimab’s effect through the loading phase matched or exceeded that of aflibercept, but it did not provide supporting figures.¹

On safety, the company reported intraocular inflammation rates of 0% with tarcocimab and 0.4% with tabirafusp-ted. Cataract adverse events occurred in 0.5% of the tarcocimab arm and 0% of the tabirafusp-ted arm, compared with 0.9% of the aflibercept arm.¹ The cataract finding matters because of the program’s history. In 2023, the GLEAM and GLIMMER trials of tarcocimab in diabetic macular edema (DME) failed. The company attributed those failures primarily to a cataract imbalance (19% with tarcocimab vs 9% with aflibercept by the primary end point).⁴

Clinical context

AMD affected an estimated 196 million people worldwide in 2020, and that number is projected to reach 288 million by 2040.⁵ Intravitreal anti-VEGF therapy is the standard of care for neovascular disease, but the injection burden limits real-world outcomes.

In the VIEW 1 and VIEW 2 trials, aflibercept 2 mg every 8 weeks after 3 monthly loading doses was noninferior to monthly ranibizumab.⁶ More recent agents have extended intervals further:

• Faricimab: Allowed dosing up to every 16 weeks in TENAYA and LUCERNE, with nearly half of patients on 16-week dosing in year 1.⁷
• Aflibercept 8 mg: Dosed every 12 or 16 weeks after loading in PULSAR and was noninferior to aflibercept 2 mg every 8 weeks.⁸

Drug background

Tarcocimab is an anti-VEGF antibody conjugated to a high-molecular-weight biopolymer through Kodiak’s antibody biopolymer conjugate (ABC) platform. The company reports a mean ocular half-life of about 20 days in humans, roughly 3 times that of approved anti-VEGF agents.¹ The formulation used in DAYBREAK also contains unconjugated protein, which is intended to produce a faster initial effect.¹

The agent’s development history in wet AMD has been uneven:

• DAZZLE (2022): This phase 2b/3 trial dosed tarcocimab at fixed 12-, 16-, or 20-week intervals and failed to show noninferiority to aflibercept every 8 weeks.²
• DAYLIGHT (557 patients): Monthly tarcocimab met noninferiority vs aflibercept every 8 weeks.⁴
• BEACON, retinal vein occlusion (RVO): Tarcocimab every 8 weeks after 2 loading doses was noninferior to monthly aflibercept at week 24.⁹
• GLOW1 and GLOW2, diabetic retinopathy: Tarcocimab was superior to sham in both trials. In GLOW2, 62.5% of patients achieved a 2-step or greater improvement on the Diabetic Retinopathy Severity Scale, compared with 3.3% of sham-treated patients (P < .0001).¹⁰

Kodiak plans to submit a Biologics License Application (BLA) in the fourth quarter of 2026 covering wet AMD, diabetic retinopathy, and RVO. The application will draw on DAYBREAK, DAYLIGHT, GLOW1, GLOW2, and BEACON.¹

Tabirafusp-ted is a bispecific molecule, also built on the ABC platform, that combines interleukin-6 (IL-6) inhibition with a VEGF trap. DAYBREAK used a 50-mg/mL formulation containing both conjugated and unconjugated protein. Kodiak plans post hoc analyses to identify which treatment-naive wet AMD subgroups may benefit from IL-6 inhibition. The company is also testing whether tabirafusp-ted is superior to aflibercept 2 mg in DME in the phase 3 ALTO trial, which plans to enroll approximately 910 patients.¹

Interpretation

The durability figure should be read carefully. The 54% of patients on 24-week dosing have no direct comparator within DAYBREAK, because aflibercept was given on a fixed label regimen. It also cannot be compared across trials that used different retreatment rules. Two investigators quoted in the company’s release are both scheduled to present the data alongside Kodiak:

• Charles Wykoff, MD, PhD, of Retina Consultants of Texas, said the tarcocimab results exceeded his expectations.
• David M. Brown, MD, of Retina Consultants of America said retreatment was guided by an AI algorithm that mirrors a zero-fluid-tolerance approach.¹

The details of that algorithm have not been published.

Limitations and next steps

These are topline, company-reported data, and they have not been peer reviewed. Efficacy magnitudes, second-year durability, and outcomes against higher-dose or bispecific comparators remain unknown. The company describes 5 positive phase 3 studies; that framing excludes DAZZLE, GLEAM, and GLIMMER. Regulatory acceptance and approval are not assured.

References

1. Kodiak Sciences Inc. Zenkuda and tabirafusp-ted meet primary endpoints in pivotal DAYBREAK trial in wAMD. News release. PR Newswire. September 28, 2026. Accessed September 28, 2026. https://www.prnewswire.com/news-releases/zenkuda-and-tabirafusp-ted-meet-primary-endpoints-in-pivotal-daybreak-trial-in-wamd-with-zenkuda-demonstrating-a-potential-new-standard-of-care-profile-with-strong-immediacy-and-sustained-clinical-effect-with-majority-of-patients-302891194.html

2. Kodiak Sciences Inc. Kodiak Sciences announces top-line results from its initial phase 2b/3 study of KSI-301 in patients with neovascular (wet) age-related macular degeneration. News release. February 23, 2022. Accessed September 28, 2026. https://ir.kodiak.com/news-releases/news-release-details/kodiak-sciences-announces-top-line-results-its-initial-phase-2b3

3. A study to evaluate the efficacy and safety of tarcocimab tedromer and tabirafusp tedromer compared to aflibercept in participants with neovascular (wet) age-related macular degeneration (DAYBREAK). ClinicalTrials.gov identifier: NCT06556368. Updated April 2026. Accessed September 28, 2026. https://clinicaltrials.gov/study/NCT06556368

4. Kodiak Sciences Inc. Kodiak Sciences announces topline results from its phase 3 studies of tarcocimab tedromer in neovascular age-related macular degeneration and diabetic macular edema. News release. July 24, 2023. Accessed September 28, 2026. https://ir.kodiak.com/news-releases/news-release-details/kodiak-sciences-announces-topline-results-its-phase-3-studies

5. Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106-e116. doi:10.1016/S2214-109X(13)70145-1. https://doi.org/10.1016/S2214-109X(13)70145-1

6. Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119(12):2537-2548. doi:10.1016/j.ophtha.2012.09.006. https://doi.org/10.1016/j.ophtha.2012.09.006

7. Heier JS, Khanani AM, Quezada Ruiz C, et al. Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials. Lancet. 2022;399(10326):729-740. doi:10.1016/S0140-6736(22)00010-1. https://doi.org/10.1016/S0140-6736(22)00010-1

8. Lanzetta P, Korobelnik JF, Heier JS, et al. Intravitreal aflibercept 8 mg in neovascular age-related macular degeneration (PULSAR): 48-week results from a randomised, double-masked, non-inferiority, phase 3 trial. Lancet. 2024;403(10432):1141-1152. doi:10.1016/S0140-6736(24)00063-1. https://doi.org/10.1016/S0140-6736(24)00063-1

9. Kodiak Sciences Inc. Form 10-K for fiscal year ended December 31, 2022. US Securities and Exchange Commission. Accessed September 28, 2026. https://www.sec.gov/Archives/edgar/data/1468748/000095017023010314/kod-20221231.htm

10. Kodiak Sciences Inc. Kodiak Sciences announces positive topline results in GLOW2, the second phase 3 study in diabetic retinopathy, demonstrating superiority of Zenkuda (tarcocimab tedromer) over sham. News release. March 26, 2026. Accessed September 28, 2026. https://ir.kodiak.com/news-releases/news-release-details/kodiak-sciences-announces-positive-topline-results-glow2-second/