Tarcocimab and Tabirafusp Meet Phase 3 Endpoints

Clinical Report: Tarcocimab and Tabirafusp Meet Phase 3 Endpoints

Overview

In the phase 3 DAYBREAK trial in treatment-naïve neovascular age-related macular degeneration (nAMD), tarcocimab tedromer and tabirafusp-ted each met the primary endpoint of noninferiority to aflibercept for mean visual acuity change at week 48. Tarcocimab was associated with extended dosing intervals for many participants, including 54% who reached 24-week dosing; the trial continues through week 96 to assess longer-term efficacy, durability, and safety.

Background

Anti-VEGF therapy is a central treatment approach for nAMD, and dosing interval is an important feature of treatment regimens. DAYBREAK compared two investigational Kodiak Sciences agents independently with aflibercept 2 mg administered every 8 weeks after three monthly loading doses. Tarcocimab is an anti-VEGF antibody–biopolymer conjugate, whereas tabirafusp-ted targets VEGF and interleukin-6. The trial used an artificial intelligence algorithm to detect central macular intraretinal and subretinal fluid to guide retreatment, reflecting the investigators’ stated treat-to-dry and maintain-dry approach.

Data Highlights

DAYBREAK measure	Tarcocimab tedromer	Tabirafusp-ted	Aflibercept comparator
Participants enrolled	667 treatment-naïve patients with nAMD
Mean BCVA gain at week 48	7.2 ETDRS letters	6.3 ETDRS letters	7.6 ETDRS letters
Primary endpoint comparison	Noninferior; P=.0007	Noninferior; P=.0036	Reference treatment
Central subfield thickness reduction	Not reported in source	131 μm; noninferior for retinal drying (P<.0001)	138 μm
Dosing interval / injections after loading	54% reached 24-week dosing; 29% received treatment every 12, 16, or 20 weeks; median 1 injection	5 mg every 8 weeks, with additional monthly treatment as indicated	Every 8 weeks; median 5 injections after loading in the tarcocimab comparison
Reported ocular safety events	No intraocular inflammation	1 case of intraocular inflammation	No intraocular inflammation
Other reported events	No endophthalmitis or occlusive retinal vasculitis cases reported

Key Findings

DAYBREAK randomized 667 treatment-naïve patients with nAMD; each investigational agent was evaluated independently against aflibercept 2 mg every 8 weeks after three monthly loading doses.
The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged across weeks 40, 44, and 48.
Tarcocimab produced a mean gain of 7.2 ETDRS letters versus 7.6 with aflibercept and met the noninferiority endpoint (P=.0007).
With tarcocimab, 54% of patients reached a 24-week dosing interval and another 29% received treatment every 12, 16, or 20 weeks; median post-loading injections were 1 versus 5 with aflibercept.
Tabirafusp-ted 5 mg, given every 8 weeks with additional monthly treatment as indicated, produced a mean BCVA gain of 6.3 letters versus 7.6 with aflibercept and met the primary endpoint (P=.0036); central subfield thickness reductions were 131 μm and 138 μm, respectively (P<.0001).
No intraocular inflammation was reported in the tarcocimab or aflibercept groups, compared with one case in the tabirafusp-ted group; no endophthalmitis or occlusive retinal vasculitis cases were reported. DAYBREAK is continuing through week 96.

Clinical Implications

The reported week-48 results support noninferiority of both investigational agents to aflibercept for the trial’s primary visual acuity endpoint, while the tarcocimab dosing data describe extended intervals achieved under DAYBREAK’s fluid-guided retreatment protocol. These are first-year findings; the trial’s planned follow-up through week 96 will evaluate longer-term efficacy, durability, and safety.

Conclusion

Both tarcocimab tedromer and tabirafusp-ted met DAYBREAK’s primary endpoint against aflibercept at week 48. Kodiak Sciences plans a multi-indication biologics license application for tarcocimab later in 2026, according to the presentation; longer-term DAYBREAK results remain pending.