Intravitreal vamikibart shows visual and anatomical improvements in uveitic macular edema study

A phase 1 clinical trial conducted at 18 sites in the US evaluating intravitreal vamikibart (RO7200220) for intravitreal vamikibart in patients with uveitic macular edema (UME) secondary to noninfectious uveitis (NIU) demonstrated improvements in best-corrected visual acuity (BCVA) and central subfield thickness (CST). The trial evaluated the safety, tolerability, and preliminary effects of intravitreal vamikibart in patients with uveitic macular edema (UME) secondary to noninfectious uveitis (NIU).

The study’s first author is Sumit Sharma, MD, of Cole Eye Institute, Cleveland Clinic in Cleveland, Ohio.

“Emerging evidence suggests that IL-6 inhibition may be an effective treatment strategy for uveitis and UME, with various IL-6R blockers being used off label,” the study authors stated. “However, currently there are no interleukin-6 (IL-6) pathway inhibitors approved for ocular conditions and no biologic IVT treatments approved for UME. Our data indicate that IVT vamikibart was associated with short-term safety and tolerability, with mean improvement in VA outcomes. Previous studies have reported anatomical and visual improvements with systemic IL-6 pathway inhibitors.”

The open-label, nonrandomized study enrolled 37 adults who received one of 3 doses of vamikibart (0.25 mg, 1 mg, or 2.5 mg) administered at baseline, week 4, and week 8, with follow-up extending to 12 weeks and beyond for observation. The primary outcomes were safety and tolerability, while exploratory measures included BCVA and CST.

“Vamikibart is a recombinant humanized immunoglobulin G2 monoclonal antibody engineered for intravitreal (IVT) administration to inhibit IL-6 activity in the eye. Vamikibart exhibits strong binding affinity for IL-6 and IL-6/IL-6R complexes, an IVT half-life of approximately 7 to 7.5 days, and limited systemic exposure, minimizing risk of systemic AEs. Vamikibart binds to site 2 of human IL-6, the region that interacts with coreceptor gp130 following its binding to transmembrane or soluble IL-6 receptors (eFigure 1 in Supplement 2). By blocking this interaction, vamikibart inhibits cis- and trans-signaling pathways and constitutes a first-in-class intravitreally administered IL-6 inhibitor.

At 12 weeks, improvements in visual and anatomical outcomes were observed across all groups. Mean BCVA letter score increased by 9.9 (8.9), corresponding to an approximate 2-line improvement. Mean CST decreased by 165.1 (147.5) µm from baseline. Improvements were reported in each dose group, with BCVA gains of +11.1, +10.3, and +8.4 letters and CST reductions of −125.0 µm, −188.1 µm, and −183.6 µm in the 0.25 mg, 1 mg, and 2.5 mg groups, respectively.

Additional anatomical findings included resolution of intraretinal fluid in most participants and complete resolution of subretinal fluid in all participants by week 12. Improvements in inflammatory markers, including anterior chamber cell and vitreous haze scores, were also observed.

Across all dose groups, vamikibart was tolerated, with 36 of 37 participants completing the 12-week treatment period. A total of 30 participants (81.1%) experienced at least one adverse event, though 3 serious adverse events were reported as unrelated to the study drug. One participant discontinued treatment due to worsening uveitis, also considered unrelated. A single treatment-related adverse event, described as transient reduction in visual acuity, was reported and resolved without intervention. No cases of retinal vasculitis were observed, and no sustained increases in IOP or new cataracts were reported.

Ocular adverse events in the study eye were reported in 19 participants (51.4%). Most were nonserious, and no participants withdrew due to adverse events.

The study did not include a control group and was limited by its small sample size, short follow-up period, and nonrandomized design. The authors note that these factors may affect interpretation of long-term safety and efficacy.

The findings provide preliminary evidence supporting the short-term safety, tolerability, and potential effects of intravitreal vamikibart in UME secondary to NIU. Two phase 3 trials are underway to further evaluate the treatment.

Reference:

1. Sharma S, Lin P, Hu A, et al. Interleukin 6 inhibition with vamikibart for uveitic macular edema: The phase 1 DOVETAIL nonrandomized clinical trial. JAMA Ophthalmology. 2026. doi:10.1001/jamaophthalmol.2026.0610