ARVO 2026: Vamikibart trials advance IL-6 inhibition in retinal disease

Interleukin-6 is increasingly recognized as a driver of inflammation in retinal disease, and a novel intravitreal agent targeting this pathway is now generating clinical trial data across two distinct indications. Among the research updates at the Association for Research in Vision and Ophthalmology (ARVO) 2026 annual meeting, May 3 to 7 in Denver, Colorado, three presentations highlighted clinical results for vamikibart, a first-in-class anti–interleukin-6 (IL-6) humanized monoclonal antibody designed for intravitreal (IVT) administration. Data were presented from the phase 2 ALLUVIUM monotherapy trial in diabetic macular edema (DME), the phase 2 BARDENAS combination trial in DME, and the phase 3 MEERKAT and SANDCAT trials in uveitic macular edema (UME) secondary to noninfectious uveitis (NIU).

ALLUVIUM: Vamikibart monotherapy vs ranibizumab in DME

Arshad M. Khanani, MD, and colleagues presented week 44/48 results from ALLUVIUM (NCT05151731), a global phase 2, randomized, double-masked, active comparator-controlled trial enrolling 394 patients with center-involving DME, of whom 259 were treatment-naive.¹ Patients were randomly assigned 1:1:1:1 to IVT vamikibart 0.25 mg every 8 weeks (Q8W), vamikibart 1.0 mg Q8W, vamikibart 1.0 mg every 4 weeks (Q4W), or ranibizumab 0.5 mg Q4W. The primary end point was mean change from baseline in best-corrected visual acuity (BCVA) averaged over weeks 44 and 48 in treatment-naive patients.

Adjusted mean BCVA change from baseline at weeks 44/48 was +7.1, +4.6, and +5.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters for vamikibart 0.25 mg Q8W, 1.0 mg Q8W, and 1.0 mg Q4W, respectively, compared with +13.0 letters for ranibizumab. The proportion of patients achieving a ≥15-letter gain in BCVA was 14.9%, 22.9%, and 15.6% across the vamikibart dose groups versus 40.0% for ranibizumab. Mean central subfield thickness (CST) reduction was −68.4, −50.8, and −67.5 μm for vamikibart doses versus −174.2 μm for ranibizumab.

Higher rates of adverse events related to intraocular inflammation were observed with vamikibart compared with ranibizumab; rates of cataract and elevated intraocular pressure (IOP) were comparable between groups. The authors concluded that vamikibart monotherapy improved vision and anatomical outcomes in patients with DME, confirming that IL-6-mediated inflammation is a relevant pathogenic pathway in DME and that IL-6 inhibition provides a clinical effect distinct from VEGF blockade. They noted that, although efficacy was less robust than ranibizumab, the findings provide a rationale for exploring the combination of anti–IL-6 and anti-VEGF therapy in DME.

BARDENAS: Vamikibart plus ranibizumab vs ranibizumab alone in DME

Roger A. Goldberg, MD, and colleagues presented week 44/48 results from BARDENAS (NCT05151744), a global phase 2, double-masked, randomized active comparator-controlled trial enrolling 187 patients with center-involving DME, of whom 124 were treatment-naive.² Patients were randomly assigned 1:1 to IVT vamikibart 1.0 mg plus ranibizumab 0.5 mg Q4W (VAM+RBZ) or ranibizumab 0.5 mg Q4W alone. The primary end point was mean change from baseline in BCVA averaged over weeks 44 and 48 in treatment-naive patients.

Adjusted mean BCVA change from baseline at weeks 44/48 was +12.8 letters for VAM+RBZ versus +9.4 letters for ranibizumab, meeting the pre-established nominal significance level of P = .1 (P = .063). The proportion of patients achieving a ≥15-letter gain in BCVA was 44.7% for VAM+RBZ versus 28.6% for ranibizumab. Mean CST reduction was −202.4 μm for VAM+RBZ versus −192.4 μm for ranibizumab. The proportion of patients achieving CST below 325 μm at weeks 44/48 was 85.1% for VAM+RBZ versus 71.4% for ranibizumab.

Higher rates of intraocular inflammation and elevated IOP were observed with VAM+RBZ compared with ranibizumab alone; cataract rates were comparable between arms, with no events of endophthalmitis or retinal detachment in the study eye reported. The authors concluded that VAM+RBZ improved vision and anatomical outcomes in patients with DME and that the findings, building on the ALLUVIUM data, provide a rationale for exploring combination anti–IL-6 and anti-VEGF therapy in DME.

MEERKAT and SANDCAT: Vamikibart vs sham in uveitic macular edema

Eduardo Uchiyama, MD, and colleagues presented week 16 outcomes from two identical phase 3 trials—MEERKAT (NCT05642312; n = 245) and SANDCAT (NCT05642325; n = 256)—evaluating IVT vamikibart 0.25 mg and 1.0 mg versus sham in patients with UME secondary to NIU.³ Vamikibart was administered 4 times monthly then pro re nata through week 48, with week 16 as the primary endpoint.

In MEERKAT and SANDCAT, respectively, mean CST change from baseline was −187.5/−209.7 μm with vamikibart 0.25 mg and −196.1/−194.7 μm with vamikibart 1.0 mg, versus −58.5/−43.5 μm with sham. The proportion of patients achieving UME resolution (CST below 325 μm) was 56.7/63.3% with 0.25 mg and 61.2/57.3% with 1.0 mg, versus 16.3/18.0% with sham. The proportion of patients achieving a ≥15-letter improvement in BCVA was 26.1/34.0% with 0.25 mg and 43.2/24.2% with 1.0 mg, versus 6.3/13.3% with sham. Mean BCVA change from baseline was +9.6/+11.9 letters with 0.25 mg and +12.8/+9.2 letters with 1.0 mg, versus +3.5/+5.0 letters with sham.

The overall incidence of serious ocular adverse events and intraocular inflammation was low, and no events of retinal occlusive vasculitis were observed. The authors concluded that vamikibart demonstrated efficacy in anatomical and vision outcomes and was well tolerated in patients with UME, describing it as a non-steroid treatment that directly targets macular edema due to ocular inflammation.

What comes next

The three presentations reported results from two phase 2 trials of vamikibart in DME (ALLUVIUM and BARDENAS) and two identical phase 3 trials in UME (MEERKAT and SANDCAT). Further data from these trials are expected as follow-up continues.

References

1. Khanani AM, Eichenbaum DA, Gallego Pinazo R, et al. Efficacy and safety of vamikibart in patients with diabetic macular edema: first results from the phase 2 ALLUVIUM trial. ARVO 2026 Annual Meeting; May 3–7, 2026; Denver, Colorado. Presentation 3334.

2. Goldberg RA, Hu A, Wykoff CC, et al. Efficacy and safety of vamikibart in combination with ranibizumab in patients with DME: first results from the phase 2 BARDENAS trial. ARVO 2026 Annual Meeting; May 3–7, 2026; Denver, Colorado. Presentation 3335.

3. Uchiyama E, Khurana R, Acharya N, et al. Efficacy and safety of vamikibart in patients with uveitic macular edema: anatomical outcomes at Week 16 in the phase 3 MEERKAT and SANDCAT trials. ARVO 2026 Annual Meeting; May 3–7, 2026; Denver, Colorado. Presentation 3849.