Q&A: KSI-101: A new dual anti-interleukin-6 and anti-VEGF protein for treating macular edema associated with inflammation

The results of a phase 1b study that evaluated a potential new treatment for macular edema associated with inflammation, KSI-101 (Kodiak Sciences, Inc.), were reported at the recent Angiogenesis, Exudation, and Degeneration 2026 at the Bascom Palmer Eye Institute, Miami. Sumit Sharma, MD, described the phase 1b end-of-study results at Angiogenesis, Exudation, and Degeneration 2026 at the Bascom Palmer Eye Institute, Miami. He is a retina and uveitis specialist at the Cole Eye Institute and serves as Vice Chair for Clinical Outcomes and Safety, Quality, and Patient Experience at Cleveland Clinic, Cleveland.

How does KOI-101 differ from other therapies that may be available to treat macular edema?

Sumit Sharma, MD: KSI-101 is a combination therapy that addresses two components of the macular edema that develops in association with inflammation, namely, interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF). Currently, the only other treatments available are corticosteroids. KSI-101 eliminates all of the adverse effects associated with steroids, ie, cataracts and increases in intraocular pressure.

What was an unexpected result of treatment of macular edema with KSI-101?

Sharma: I was especially surprised by the speed with which the fluid resolved in the treated eyes. At week 1 after the first dose, more than three-quarters of the eyes were free of fluid. That is a fantastic result that was not seen in other clinical trials.

What else was outstanding about this treatment?

Sharma: The results showed the durability of KSI-101. At the 16-week timepoint, which was 4 weeks after the previous injection, 96% of the eyes were fluid-free, and at week 24, 80% of those eyes were fluid-free; 16% of the eyes had slight fluid recurrences. No recurrence of fluid was seen in 80% of eyes during 12 weeks without treatment. This is a very encouraging result.

What is the next step for the drug?

Sharma: Two phase 3 studies, the PEAK and PINNACLE studies, are currently enrolling patients. The studies will evaluate the treatment effects with the 5- and 10-mg doses of KSI-101.

What key points would you like ophthalmologists to know about the results achieved with KSI-101 in the phase 1b clinical trial?

Sharma: KOI-101, a combination anti-interleukin-6 and anti-vascular endothelial growth factor molecule, was able to resolve macular edema in almost 100% of a heterogeneous group of patients; 96% of eyes had complete resolution of macular edema after four injections. That outcome was maintained during an off-treatment observation period of 12 weeks in the vast majority of eyes with a fantastic safety profile.