Kyowa Kirin KHK4951, an investigational nanocrystal ophthalmic suspension built on the tyrosine kinase inhibitor tivozanib, has generated closely watched Phase 2 topline results in patients with neovascular age-related macular degeneration (nAMD). Kyowa Kirin Co., Ltd. (TSE:4151, President and CEO Abdul Mullick) disclosed the findings from its global Study 4951-002 on September 8, 2026, positioning the eye drop as a potential non-invasive maintenance therapy for patients who have already responded to anti-VEGF treatment.
The randomized, double-masked, multicenter trial enrolled patients who first demonstrated a favorable response during a run-in period of intravitreal anti-VEGF injections before being assigned to one of three Kyowa Kirin KHK4951 dosing regimens. Across all three dose groups, approximately 65% to 69% of participants avoided the study’s composite primary event, a loss of 15 or more letters in best-corrected visual acuity (BCVA) or the need for rescue treatment, through Week 52.
Despite that encouraging retention rate, the study did not demonstrate statistical superiority of the high-dose regimen over the low-dose regimen, the comparison that had been designated as the primary endpoint. As a result, Kyowa Kirin confirmed that Study 4951-002 did not meet its primary endpoint, even though mean BCVA and central subfield thickness (CST) were generally maintained among patients who completed the full observation period.
“The interim results from the KHK4951-002 study provide important insights and support further investigation,” said Dante Pieramici, M.D., Medical Director of Clinical Research at California Retina Consultants in Santa Barbara, California. He noted that the absence of a true control arm remains a key limitation requiring careful interpretation, but added that many patients maintained visual outcomes over roughly a year following their initial anti-VEGF treatment, an encouraging signal given the ongoing treatment burden that frequent intravitreal injections place on nAMD patients.
Kyowa Kirin KHK4951 Clinical Study Design and Methodology
Study 4951-002 was designed specifically to test whether an eye drop-based maintenance regimen could extend the benefit of anti-VEGF therapy without repeated injections. Before randomization, every enrolled patient received three intravitreal injections of aflibercept 2 mg to establish a stable disease baseline. Patients who responded favorably during this run-in period were then randomized into the Kyowa Kirin KHK4951 dosing arms described below.
The trial’s primary endpoint compared treatment groups on the proportion of patients experiencing either a loss of 15 or more letters in BCVA or requiring rescue treatment between Week 8 and Week 52, a standard measure used across nAMD maintenance studies. Secondary assessments tracked anatomical changes through CST, a retinal-thickness measurement obtained by optical coherence tomography that reflects fluid leakage from abnormal blood vessels beneath the macula.
Yoshifumi Torii, M.D., Ph.D., Chief Medical Officer of Kyowa Kirin, said that many patients across all dose groups, including the low-dose group, maintained their vision over the approximately one-year observation period, and that mean BCVA remained generally stable among those who completed the study. He acknowledged that the predefined dose-response relationship was not demonstrated, but pointed to the anatomical CST data and the overall safety evaluation as sources of meaningful insight for future maintenance-treatment strategies.
Kyowa Kirin KHK4951 Safety Profile and Tolerability Findings
Alongside the efficacy readout, Kyowa Kirin KHK4951 was reported as generally well tolerated across the full dose range studied, including the highest regimen of 2.0% twice daily. Company disclosures state that no new safety signals were identified during the 52-week observation period, a notable finding given that the study evaluated a topically administered tyrosine kinase inhibitor rather than an intravitreal biologic.
The most commonly noted ocular findings were dry eye and punctate keratitis, both observed in some patients across the dosing arms. Systemically, investigators paid particular attention to blood pressure, since VEGF pathway inhibition is associated with hypertension risk in other therapeutic settings; the study found no clinically meaningful trend toward blood pressure elevation among Kyowa Kirin KHK4951-treated patients.
Kyowa Kirin KHK4951 Outlook and Next Steps for nAMD Treatment
Looking beyond Study 4951-002, Kyowa Kirin KHK4951 remains part of a broader tivozanib eye-drop development program that also includes an active Phase 2 study in diabetic macular edema (DME), registered separately under Study 4951-003. The company has consistently framed KHK4951 as an exploratory step toward reducing the treatment burden associated with chronic retinal disease, rather than a direct replacement for existing anti-VEGF injections in the near term.
That burden is substantial at a population level. Age-related macular degeneration overall is estimated to affect approximately 200 million people worldwide, a figure Kyowa Kirin projects will rise to roughly 290 million by 2040 as populations age. In Japan alone, more than 100,000 patients are estimated to live with nAMD today, a number the company expects to keep climbing.
Kyowa Kirin has stated that KHK4951 has not been approved in any country or region and that its safety and efficacy have not yet been established through pivotal, controlled trials. Management said the company remains committed to carefully evaluating the knowledge gained from Study 4951-002 as it weighs next steps for the tivozanib eye-drop program, including how the anatomical and safety findings might inform a future, more rigorously controlled study design.
For a company positioning itself as a global specialty pharmaceutical business, the topline data represent a mixed but not discouraging checkpoint. Kyowa Kirin KHK4951 did not clear its statistical bar for a dose-response relationship, yet the retention of vision across all three arms, paired with a clean safety profile through 52 weeks, gives the company a rationale to continue investing in eye drop-based maintenance therapy as an alternative to lifelong intravitreal injections for nAMD patients.
Kyowa Kirin, a Japan-based global specialty pharmaceutical company that has invested in drug discovery and biotechnology innovation for more than 70 years, said the results will inform ongoing efforts across its JAPAC, North America, and EMEA regions to bring new treatment options to people living with retinal disease.
