Interleukin 6 Inhibition With Vamikibart for Uveitic Macular Edema

Key Takeaways

• Intravitreal vamikibart was associated with week 12 improvement in visual acuity and retinal thickness across all three dose groups.
• Ocular adverse events were reported in 19 of 37 participants, with one unrelated serious event, one treatment-related transient visual acuity reduction, and no reported retinal vasculitis.
• The authors described the findings as preliminary support for safety, tolerability, and potential effects, while phase 3 development continues.

Adults with uveitic macular edema secondary to noninfectious uveitis gained a mean 9.9 best-corrected visual acuity letters by week 12 after intravitreal vamikibart in the phase 1 DOVETAIL trial. That change corresponds to roughly a 2-line visual improvement in this early readout. Vamikibart is an anti–interleukin 6 monoclonal antibody administered by intravitreal injection.

DOVETAIL was a multipart, multicenter, open-label, multiple-ascending-dose, phase 1, nonrandomized clinical trial conducted at 18 U.S. sites from July 2019 to November 2023. Eligible participants were adults with uveitic macular edema secondary to noninfectious uveitis and optical coherence tomography central subfield thickness of at least 325 µm. Thirty-seven participants entered the 0.25-mg, 1-mg, and 2.5-mg groups, and intravitreal vamikibart was given on day 1, week 4, and week 8. Primary outcomes were safety and tolerability, while best-corrected visual acuity and central subfield thickness were exploratory outcomes.

The study enrolled 12 participants in the 0.25-mg group, 12 in the 1-mg group, and 13 in the 2.5-mg group. Thirty-six of 37 participants continued treatment through 12 weeks, and the mean age was 63.5 years, with 59.5% female. At week 12, mean central subfield thickness decreased by 165.1 µm overall, while best-corrected visual acuity changed by 11.1, 10.3, and 8.4 letters across ascending doses. Central subfield thickness fell by 125.0, 188.1, and 183.6 µm in the same groups, showing parallel visual and anatomic improvement across dose levels.

Ocular adverse events occurred in the study eye during follow-up. Investigators identified one serious adverse event of worsening uveitis, which was judged unrelated to study drug, and one treatment-related transient reduction in visual acuity. No occlusive or nonocclusive retinal vasculitis was reported, and observation continued after dosing to week 20 in the 2.5-mg group and week 36 in the lower-dose groups. The authors described the findings as preliminary support for safety, tolerability, and potential effects, and noted that MEERKAT and SANDCAT are underway.