Kodiak's Zenkuda and Tabirafusp-Ted Hit Phase 3 DAYBREAK Endpoints in Wet AMD
核心洞察
Both Zenkuda (tarcocimab tedromer) and tabirafusp alfa tedromer (搜索) met the primary endpoint of noninferiority in best corrected visual acuity versus aflibercept at one year in the phase 3 DAYBREAK study.
Zenkuda achieved its vision endpoint with a p-value of 0.0007, and 54% of patients reached a 24-week dosing interval under strict treat-to-dryness retreatment criteria.
Tabirafusp-ted, an anti-IL-6 and VEGF (搜索)-trap bispecific, met its vision endpoint at P = .0036 and its anatomical secondary endpoint at P < .0001, with post hoc subgroup analyses planned.
Kodiak Sciences reported that two investigational agents, Zenkuda (tarcocimab tedromer) and tabirafusp alfa tedromer (搜索) (tabirafusp-ted, also known as KSI-501), both met their primary endpoints in the pivotal phase 3 DAYBREAK study in patients with wet age-related macular degeneration (搜索). Both therapies were noninferior to Eylea (aflibercept, Regeneron) for vision gains at one year.
Zenkuda met the primary endpoint with a p-value of 0.0007, demonstrating vision gains alongside rapid and sustained retinal drying. More than half of patients, 54%, reached a six-month, or 24-week, dosing interval at year one under strict treat-to-dryness retreatment criteria. Kodiak said the design was intended to resemble real-world retinal specialist practice by using retinal fluid as the marker for retreatment.
Tabirafusp-ted met its vision primary endpoint with a p-value of 0.0036 and its anatomical key secondary endpoint with a p-value below 0.0001. Kodiak plans post hoc analyses to identify which treatment-naive wet AMD patient subgroups may benefit most from IL-6 inhibition.
Mechanism and Durability
Zenkuda is an investigational anti-VEGF (搜索) biopharmaceutical built on Kodiak's proprietary antibody biopolymer conjugate (ABC) platform and is designed to maintain more durable drug levels. According to the company, it has a mean ocular half-life of about 20 days, roughly three times longer than approved anti-VEGF therapies. Kodiak ultimately aims for a flexible dosing label ranging from one month to six months across retinal vascular diseases.
Tabirafusp-ted is an anti-IL-6, VEGF (搜索)-trap bispecific also built on the ABC platform.
"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 (搜索) and retinal vein occlusion," said Victor Perlroth, M.D., chief executive officer of Kodiak Sciences.
J. Pablo Velazquez-Martin, M.D., chief medical officer of Kodiak Sciences, said the readout came "four years and seven months after our first Phase 3 readout," adding that "DAYBREAK demonstrated the attributes we designed Zenkuda to achieve: rapid disease control in wet AMD and the potential for six-month durability under stringent treat-to-dryness retreatment criteria."
Charles Wykoff, M.D., Ph.D., chairman of research at Retina Consultants of Texas and professor of clinical ophthalmology and deputy chair of ophthalmology at Houston Methodist Hospital, said: "More than half of patients reached a 24-week dosing interval using strict treat-to-dry retreatment criteria. This combination of immediacy, flexibility and true durability is unique and differentiated." He added that the data "bring us closer to the best possible outcomes with fewer injections."
Safety Findings
Zenkuda demonstrated a favorable safety profile in the study. No intraocular inflammation was reported among Zenkuda-treated patients, and the cataract adverse-event rate was 0.5%, compared with 0.9% for aflibercept. Tabirafusp-ted was also well tolerated, with a 0.4% intraocular inflammation rate and no reported cataract adverse events, compared with the 0.9% cataract rate for aflibercept.
Regulatory Path and Broader Program
Kodiak plans to submit a biologics license application for Zenkuda in the fourth quarter of 2026, covering three indications: wet AMD, supported by the phase 3 DAYBREAK and DAYLIGHT studies; diabetic retinopathy (搜索), supported by the phase 3 GLOW and GLOW2 studies; and macular edema following retinal vein occlusion (搜索), supported by the phase 3 BEACON study. The DAYBREAK results bring Zenkuda's tally to five completed successful phase 3 pivotal studies.
Tabirafusp-ted is being advanced in parallel in the phase 3 ALTO study in diabetic macular edema (搜索). The approximately 910-patient global study is evaluating whether the bispecific can demonstrate superiority over aflibercept and includes regimens allowing individualized dosing intervals of up to 24 weeks.
Kodiak also expects a phase 3 topline readout for KSI-101 in December 2026 in patients with macular edema secondary to inflammation. The company said its late-stage portfolio could potentially result in marketing authorization for both Zenkuda and KSI-101 by the end of 2027 or early 2028.