AFLIBERCEPT-JBVF

Two of Kodiak Sciences’ drug candidates have matched Eylea in a phase 3 clinical trial, positioning the biotech to seek FDA approval of one of the eye disease assets this year. The Daybreak study compared tarcocimab tedromer and tabirafusp alfa tedromer to aflibercept, a VEGF inhibitor that Regeneron sells as Eylea, in wet age-related macular degeneration (wAMD). After one year of treatment, both of Kodiak's candidates performed as well as aflibercept on the primary endpoint, which assessed vision gains. Investors seemed pleased, sending the biotech's stock up 128% to $72.99 when markets opened Monday from a Friday closing price of $32.35. Kodiak plans to file for FDA approval of tarcocimab, an anti-VEGF drug also called Zenkuda, in the fourth quarter. The multi-indication submission will include results from five phase 3 trials in wAMD, diabetic retinopathy and retinal vein occlusion. “The Zenkuda results exceeded my expectations, delivering the clinical profile retina specialists are seeking: rapid vision and anatomic improvements comparable to aflibercept during loading, followed by meaningfully longer intervals between treatment for a majority of patients, while maintaining optimal fluid control,” Houston Methodist Hospital’s Charles Wykoff, M.D., Ph.D., a surgical retina specialist, said in a statement. Kodiak used an AI-guided retreatment algorithm to inform tarcocimab dosing. More than half of the patients were maintained on 24-week dosing through year one. Patients on aflibercept received treatment every eight weeks. The biotech has yet to share detailed Daybreak data comparing tarcocimab to the control, although it said the drug candidate showed “strong immediacy of clinical effect, matching and/or exceeding that of the aflibercept comparator through the loading phase.” Kodiak also reported strong durability of clinical effect and a favorable safety profile, with a numerically lower rate of cataracts than aflibercept. An “unexpected increase in cataracts” temporarily ended tarcocimab development in 2023. The biotech restarted development later that year in response to non-proliferative diabetic retinopathy data. Buoyed by the readout, Kodiak embarked on a renewed late-phase program that has taken it to the cusp of an FDA filing. While investors were enthusiastic, the topline readout left unanswered questions about tarcocimab’s chances in a competitive field. Patents on aflibercept have expired, meaning Kodiak will compete with biosimilars such as Biocon’s Yesafili. As well as contending with lower-cost biosimilar competition, Kodiak will face up against branded rivals such as Regeneron’s Eylea HD and Roche’s Vabysmo. Kodiak’s Daybreak press release focused on tarcocimab rather than tabirafusp, an anti-IL-6, VEGF-trap bispecific therapy. Like tarcocimab, tabirafusp matched aflibercept on the primary endpoint. Kodiak will run post-hoc analyses to identify which treatment-naïve wAMD patient sub-groups can benefit from IL-6 inhibition. A phase 3 superiority trial is comparing tabirafusp to aflibercept in diabetic macular edema.