Kodiak's Zenkuda and Tabirafusp-ted Match Aflibercept in Phase 3 Wet AMD Trial

Kodiak Sciences said on September 28 that both of its investigational eye drugs, Zenkuda (tarcocimab tedromer) and tabirafusp-ted (KSI-501), met the primary endpoint of the Phase 3 DAYBREAK trial in wet age-related macular degeneration (wet AMD), according to the company's topline announcement. Each drug achieved vision gains that were noninferior to the standard therapy aflibercept at one year.

The results are company-reported topline data. Kodiak did not disclose mean letter gains in the announcement, and the detailed results were to be discussed on a company webcast.

The DAYBREAK trial

DAYBREAK (NCT06556368) is a noninferiority study with parallel Zenkuda and tabirafusp-ted arms and an aflibercept comparator arm, in patients with wet AMD who had not been treated before. The primary endpoint was the change in visual acuity from baseline to the average of weeks 40, 44 and 48.

Patients on Zenkuda received four monthly loading doses and then individualized dosing every 4 to 24 weeks as needed. Retreatment followed a treat-to-dryness approach that used the presence of retinal fluid as the disease activity marker. Patients on tabirafusp-ted received fixed dosing every 8 weeks after loading, with additional doses up to monthly if needed. Aflibercept was dosed per its label.

Zenkuda met the primary endpoint with a p-value of 0.0007, and 54% of Zenkuda patients reached a 6-month dosing interval at year one, the company said. Tabirafusp-ted, a bispecific drug aimed at both VEGF and IL-6, met the vision primary endpoint (p=0.0036) and an anatomical key secondary endpoint (p<0.0001). Kodiak said it plans post-hoc analyses to identify which patient subgroups may benefit from IL-6 inhibition.

On safety, Kodiak reported an intraocular inflammation rate of 0% with Zenkuda and 0.4% with tabirafusp-ted. Cataract adverse events occurred in 0.5% of Zenkuda patients and none on tabirafusp-ted, compared with 0.9% on aflibercept.

A program with setbacks

The readout is the first positive wet AMD result for tarcocimab on an extended, individualized regimen, Ophthalmology Times reported. In 2022, the Phase 2b/3 DAZZLE trial, which used fixed 12-, 16- or 20-week intervals, failed to show noninferiority to aflibercept every 8 weeks. In 2023, the GLEAM and GLIMMER trials in diabetic macular edema also failed, which the company attributed mainly to an imbalance in cataracts, the publication reported.

The publication also noted that Kodiak said Zenkuda's effect through the loading phase matched or exceeded aflibercept's, but did not provide supporting figures.

"The strength of these DAYBREAK data positions us for the next stage of Kodiak's evolution, as we prepare for the planned commercialization of Zenkuda as a potential best-in-class therapy for patients with wet AMD, diabetic retinopathy and retinal vein occlusion," said Victor Perlroth, Kodiak's chief executive officer.

Next steps

Kodiak plans to submit a biologics license application for Zenkuda in the fourth quarter of 2026, drawing on five Phase 3 studies: DAYBREAK and DAYLIGHT in wet AMD, GLOW1 and GLOW2 in diabetic retinopathy, and BEACON in macular edema following retinal vein occlusion. Tabirafusp-ted is being tested against aflibercept in diabetic macular edema in the Phase 3 ALTO study, which is enrolling. The company expects topline data in December 2026 from the Phase 3 PEAK study of a third drug, KSI-101, in macular edema secondary to inflammation.