Kodiak's Zenkuda and tabirafusp-ted hit primary endpoints in pivotal DAYBREAK trial in wet AMD
核心洞察
Zenkuda (tarcocimab tedromer) met the DAYBREAK primary endpoint with a p-value of 0.0007, showing vision gains and retinal drying in wet AMD.
Tabirafusp-ted (KSI-501) met its vision primary endpoint at p=0.0036 and the anatomical key secondary endpoint at p<0.0001.
Both agents achieved non-inferiority in vision gains versus aflibercept at year one, with 54% of Zenkuda patients on 6-month dosing.
Kodiak Sciences reported that both Zenkuda (tarcocimab tedromer) and tabirafusp alfa tedromer (搜索) (tabirafusp-ted, KSI-501) met their primary endpoints in the Phase 3 DAYBREAK study in patients with wet age-related macular degeneration (搜索) (wAMD). Both investigational agents achieved non-inferiority in vision gains compared with aflibercept at year one, according to topline results announced on September 28, 2026.
Zenkuda met the primary endpoint with a p-value of 0.0007, demonstrating meaningful vision gains alongside rapid and sustained retinal drying. In the study, 54% of patients achieved a 6-month dosing interval at year one while being managed under strict treat-to-dryness, real-world retreatment criteria. The company described the result as establishing a first-line benchmark in wAMD.
Tabirafusp-ted, an anti-IL-6, VEGF (搜索)-trap bispecific built on the same antibody biopolymer conjugate (ABC) platform, met the vision primary endpoint with a p-value of 0.0036 and the anatomical key secondary endpoint with a p-value of less than 0.0001.
Trial design and dosing
DAYBREAK is a non-inferiority study evaluating parallel investigational arms of Zenkuda and KSI-501 against active comparator aflibercept. Patients randomized to Zenkuda received four monthly loading doses followed by individualized dosing every 4 to 24 weeks on an as-needed basis. Individualized dosing was determined by a treat-to-dryness proactive approach using the presence of retinal fluid as a disease activity marker, rather than a combination of central subfield thickness and vision loss.
Patients randomized to tabirafusp-ted received fixed every-8-week dosing with additional individualized dosing up to monthly after four monthly loading doses. The tabirafusp-ted arm used the same treat-to-dryness approach coupled with fixed intensive proactive dosing. The primary endpoint for that arm was non-inferiority in change in visual acuity from baseline to the average of Week 40, 44 and 48. Aflibercept patients were dosed per label. The trial is registered on clinicaltrials.gov under identifier NCT06556368.
Zenkuda's specific objectives in DAYBREAK were to assess safety, meet the primary endpoint of non-inferiority of best corrected visual acuity, explore the strength of fluid control vision gain through the loading phase, and demonstrate a differentiated real-world durability profile.
Safety findings
Both agents demonstrated safety consistent with the established safety profile of aflibercept. Zenkuda showed a 0% intraocular inflammation rate and a 0.5% cataract adverse event rate, compared with 0.9% for cataract in the aflibercept comparator arm. Tabirafusp-ted showed a 0.4% intraocular inflammation rate and a 0% cataract adverse event rate, also against 0.9% for aflibercept.
Durability and mechanism
Zenkuda is an investigational anti-VEGF (搜索) biopharmaceutical built on Kodiak's ABC platform for intravitreal administration. It has a mean ocular half-life in humans of about 20 days, roughly three times that of approved anti-VEGF therapies, and is designed to maintain potent drug levels in ocular tissues for longer. The company's stated objective is a flexible 1-month through 6-month label for all patients with retinal vascular disease, including treatment-naive, treatment-experienced, mild and severe patients.
Charles Wykoff, M.D., Ph.D., Chairman of Research at Retina Consultants of Texas, said the Zenkuda results exceeded his expectations, delivering rapid vision and anatomic improvements comparable to aflibercept during loading followed by meaningfully longer intervals between treatment for a majority of patients while maintaining fluid control. "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 said.
David M. Brown, M.D., Chief Medical Officer of Retina Consultants of America, noted that 20 years after approval of Lucentis (ranibizumab) for wet AMD, the goal remains robust anatomic disease control and maximal visual gains sustained with less frequent dosing. He said Zenkuda pairs free protein for immediate disease control with antibody conjugated to a high-molecular-weight biopolymer, and that DAYBREAK's criteria require retreatment for any detectable fluid on OCT. "The goal is not one-size-fits-all dosing, but extending each patient to the longest effective interval their biology allows," he said.
Regulatory path and pipeline
Kodiak plans to submit Zenkuda data to regulatory authorities in the fourth quarter of 2026 from five positive Phase 3 studies: DAYBREAK and DAYLIGHT in wAMD, GLOW1 and GLOW2 in diabetic retinopathy (搜索) (DR), and BEACON in macular edema following retinal vein occlusion (搜索) (RVO). The planned submission is a three-indication biologics license application.
In GLOW1 and GLOW2, 100% of DR patients were on extended 6-month dosing at year one. In BEACON, Zenkuda-treated patients were dosed at 8-week intervals during the first 6 months, versus 4-week intervals for aflibercept; in the second 6 months identical retreatment criteria were used in both arms, and nearly half of Zenkuda patients required no treatment while achieving similar vision and anatomical outcomes to aflibercept at one year.
"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 (搜索)," said Victor Perlroth, M.D., Chief Executive Officer of Kodiak Sciences.
J. Pablo Velazquez-Martin, M.D., Chief Medical Officer, said the company plans to submit the Zenkuda BLA later this year and that post-hoc analyses are planned to identify which treatment-naive wAMD patient subgroups can benefit from IL-6 inhibition.
Tabirafusp-ted is being accelerated in diabetic macular edema (搜索). The registrational Phase 3 ALTO study is enrolling approximately 910 patients, treatment-naive or previously treated, with visual impairment secondary to center-involved DME. Participants are randomized 5:3:5 to tabirafusp-ted 5 mg every 8 weeks with monthly assessment for additional individualized dosing after six monthly loading doses; tabirafusp-ted 5 mg on an individualized regimen of every 4 to 24 weeks after six monthly loading doses; or aflibercept 2 mg every 8 weeks after five monthly loading doses. The primary endpoint is mean change in best-corrected visual acuity from baseline to the average of Week 48 and Week 52, with the proportion of patients improving two or more steps on the DRSS at Week 48 as the key secondary endpoint. Participants will be treated and followed for approximately 96 weeks.
Kodiak's third late-stage asset, KSI-101, is being developed for macular edema secondary to inflammation (搜索) (MESI), with first topline readout from the Phase 3 PEAK study expected in December 2026. PEAK is evaluating KSI-101 for superiority against sham-treated patients, and the company plans to file a BLA for KSI-101 in the second quarter of 2027. Kodiak stated it wholly owns global rights to all three late-phase assets.