Kodiak Sciences Says Both Drugs Met Primary Endpoints in Phase 3 Wet-AMD Trial

Kodiak Sciences said both of its investigational drugs in the Phase 3 DAYBREAK study met the trial’s primary endpoint in patients with treatment-naive wet age-related macular degeneration, or wet AMD. Zenkuda, also known as tarcocimab tedromer, and tabirafusp alfa tedromer, formerly KSI-501, each produced vision gains that were non-inferior to aflibercept at one year, according to topline results released Monday.

The readout gives Kodiak a positive result for two separate development programs from the same pivotal study. The primary endpoint measured the change in best-corrected visual acuity from baseline using the average of Weeks 40, 44 and 48. Kodiak reported a p-value of 0.0007 for Zenkuda and 0.0036 for tabirafusp-ted on the vision endpoint.

Zenkuda matched aflibercept on vision while extending dosing for many patients

In its DAYBREAK topline announcement, Kodiak said 54% of patients receiving Zenkuda reached a 24-week, or roughly six-month, dosing interval at year one. Patients assigned to Zenkuda first received four monthly loading doses and then moved to individualized dosing every four to 24 weeks as needed. Retreatment was driven by a treat-to-dryness approach that used the presence of retinal fluid as a disease-activity marker.

That durability result is important to Kodiak’s proposed profile for Zenkuda because anti-VEGF treatment for wet AMD can require repeated injections into the eye. The study was designed to test whether the drug could preserve vision outcomes while allowing longer intervals for patients whose disease remained controlled. Kodiak said Zenkuda matched or exceeded the aflibercept comparator through the loading phase and maintained comparable vision gains through the one-year primary endpoint.

The company also reported no cases of intraocular inflammation in the Zenkuda arm and a 0.5% cataract adverse-event rate, compared with 0.9% for aflibercept. Those figures are company-reported topline safety results rather than an FDA review, and Zenkuda remains investigational. Kodiak said the observed safety profile was consistent with the established safety profile of aflibercept.

Zenkuda is an anti-VEGF biologic built on Kodiak’s antibody biopolymer conjugate platform. The company says the drug has a mean ocular half-life of about 20 days in humans and is intended to maintain therapeutic exposure in ocular tissues for longer periods. DAYBREAK was the final anticipated Phase 3 study in Kodiak’s current Zenkuda program after earlier pivotal studies in wet AMD, diabetic retinopathy and retinal vein occlusion.

Tabirafusp-ted also cleared the vision endpoint and an anatomical secondary endpoint

Tabirafusp-ted met the same non-inferiority vision endpoint against aflibercept, with Kodiak reporting a p-value of 0.0036. The company also said the drug met an anatomical key secondary endpoint with a p-value of less than 0.0001. Kodiak did not present the result as evidence that tabirafusp-ted was superior to aflibercept on the primary vision measure.

The tabirafusp-ted arm used a different dosing strategy from Zenkuda. After four monthly loading doses, patients received fixed dosing every eight weeks with the possibility of additional individualized dosing, as frequently as monthly, when retreatment criteria were met. The DAYBREAK study is registered as NCT06556368 on ClinicalTrials.gov.

For safety, Kodiak reported a 0.4% intraocular inflammation rate in the tabirafusp-ted arm and no cataract adverse events, versus a 0.9% cataract rate with aflibercept. As with Zenkuda, those numbers come from Kodiak’s topline disclosure and will need to be considered alongside the complete study dataset and any later regulatory review.

Tabirafusp-ted is designed to inhibit both VEGF and interleukin-6, or IL-6. Kodiak plans post-hoc analyses to identify whether particular treatment-naive wet AMD subgroups may derive additional benefit from IL-6 inhibition. The company is also testing the drug in diabetic macular edema in the ongoing Phase 3 ALTO study, where the goal is to evaluate whether the dual-target therapy can outperform aflibercept rather than merely establish non-inferiority.

The DAYBREAK result puts Kodiak’s planned Zenkuda filing next in line

The immediate regulatory focus is Zenkuda. Kodiak said it plans to submit a three-indication biologics license application in the fourth quarter of 2026 using data from 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. The company had previously said in its second-quarter regulatory filing that it intended to include DAYBREAK in the application if the study was successful.

Meeting a Phase 3 primary endpoint does not mean a drug has been approved. The FDA will evaluate the full application, including efficacy, safety, manufacturing and other supporting information, if and when Kodiak files it. Kodiak is still a precommercial biotechnology company, so the planned Zenkuda submission is a central step in determining whether the program can move from clinical development toward a marketed product.

The result also changes the evidence base around Zenkuda from the position Kodiak described before the readout. In its August quarterly filing, the company listed four successful Phase 3 pivotal studies for the drug and described DAYBREAK as the remaining Phase 3 study in the program. With Monday’s topline result, Kodiak now counts five positive Phase 3 studies across three retinal vascular indications.

DAYBREAK also provides a pivotal wet AMD result for tabirafusp-ted, but Kodiak’s near-term plans for that drug remain focused on additional analysis and the separate ALTO program in diabetic macular edema. The company said it will examine DAYBREAK subgroups to understand where IL-6 inhibition may add value in wet AMD. For investors, the next concrete Zenkuda milestone is the planned fourth-quarter BLA submission, while the broader pipeline continues with ALTO enrollment and another Phase 3 readout for Kodiak’s KSI-101 program expected in December 2026.