Kodiak Sciences (NASDAQ:KOD) reported that its Phase III DAYBREAK study met primary endpoints for two investigational treatments in treatment-naïve patients with wet age-related macular degeneration, or wet AMD, with both therapies demonstrating statistical equivalence to aflibercept on visual-acuity outcomes.
The company presented results for Zenkuda, also known as tarcocimab, and tabirafusp-ted, also called KSI-501 or tedromer. DAYBREAK used a single aflibercept control arm but evaluated each investigational therapy independently under separate statistical analysis plans.
Zenkuda results and durability
Charles Wykoff, chairman of research at Retina Consultants of America, said the study’s retreatment protocol was designed to identify very small amounts of intraretinal or subretinal fluid through an artificial-intelligence-based imaging analysis. The criteria did not require patients to experience vision loss or to meet a specified central subfield thickness threshold before retreatment.
At week 48, patients receiving aflibercept gained an average of 7.6 letters of visual acuity, compared with a 7.2-letter gain for Zenkuda. Wykoff said the primary endpoint was met with high statistical significance, demonstrating non-inferiority and equivalence between the treatments.
Central subfield thickness outcomes also showed overlapping trajectories during the study, according to the presentation. Wykoff said this supported the view that Zenkuda achieved disease control during the loading phase comparable with aflibercept.
Among Zenkuda-treated patients, 54% reached a 24-week, or six-month, dosing interval by the 48-week endpoint. About 30% reached dosing intervals of 12, 16 or 20 weeks, while roughly 15% to 17% required treatment every four or eight weeks.
There were no reported cases of intraocular inflammation, occlusive retinal vasculitis or endophthalmitis in either the Zenkuda or aflibercept arms of that comparison. The Zenkuda arm had one cataract event, or 0.5%, compared with two events, or 0.9%, in the aflibercept arm.
Tabirafusp-ted also meets endpoint
In the separate tabirafusp-ted analysis, patients received four monthly 5 mg doses followed by fixed every-eight-week treatment. Patients could also receive additional monthly doses if the same AI-based analysis identified disease activity.
At the end of the assessment period, aflibercept patients gained an average of 7.6 letters, while tabirafusp-ted patients gained 6.3 letters. Kodiak said the study met its primary endpoint, demonstrating non-inferiority and equivalence in visual acuity. The company cited a P value of 0.0036 for the non-inferiority analysis.
Tabirafusp-ted also demonstrated non-inferiority and equivalence to aflibercept on central subfield thickness, according to Wykoff. In the safety results, there was one intraocular inflammatory event in the tabirafusp-ted group, representing 0.4% of patients. Neither arm reported occlusive retinal vasculitis or endophthalmitis, while two cataract events occurred in the aflibercept group and none occurred in the tabirafusp-ted group.
Wykoff said further analysis would be needed to identify whether particular wet AMD subgroups may benefit more from the therapy’s interleukin-6 inhibition mechanism. David Brown, a medical and surgical retina specialist at Retina Consultants of America, said inflammatory pathways may have a more prominent role in diabetic macular edema, or DME, than in wet AMD.
Development and regulatory plans
Chairman and Chief Executive Officer Victor Perlroth said Kodiak plans to submit a multi-indication biologics license application for Zenkuda this year. The proposed filing would cover wet AMD, diabetic retinopathy and retinal vein occlusion, supported by five positive Phase III trials, according to the company.
Kodiak is also enrolling patients in its Phase III ALTO study of tabirafusp-ted in DME. Pablo Velazquez-Martin, Kodiak’s chief medical officer, said the study is powered for superiority and is intended to assess the potential role of IL-6 inhibition in the inflammatory vascular disease setting.
The company also said it remains on track to release top-line data before Christmas from the PEAK study of KSI-101 in macular edema secondary to inflammation. A second pivotal analysis from the PEAK and PINNACLE program is expected in the second quarter of 2027.
Perlroth said Kodiak aims to transition from a pre-commercial company to a commercial-stage company through potential Zenkuda approval, while continuing development of KSI-101 and tabirafusp-ted.
About Kodiak Sciences (NASDAQ:KOD)
Kodiak Sciences Inc (NASDAQ: KOD) is a clinical-stage biopharmaceutical company focused on developing medicines for serious retinal diseases. The company’s research is centered on its Antibody Biopolymer Conjugate (ABC) platform, which is designed to combine antibody-based therapies with biopolymer technology to potentially extend the duration of treatment in the eye.
Kodiak’s lead programs have focused on ophthalmic diseases involving abnormal blood-vessel growth or leakage, including wet age-related macular degeneration, diabetic macular edema and retinal vein occlusion.
