Treatment for Macular Oedema Secondary to Inflammation

Preliminary results from a phase 1b clinical trial show that intravitreal treatment with KSI-101, a bispecific trap-antibody inhibiting both interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), was associated with robust anatomic and visual improvement in patients with macular oedema secondary to inflammation (MESI), irrespective of the location of inflammation or the specific aetiology.

“MESI is a heterogeneous group of diseases with the shared pathophysiology of inflammation and blood-retinal barrier disruption and associated macular oedema with visual impairment. Diseases in this new category include the classic uveitic macular oedemas, as well as other aetiologies such as postoperative macular oedema and choroidal neovascularisation secondary to inflammation,” said Charles C Wykoff MD, PhD. “The encouraging first-time results in the phase 1b [trial] have led to the launch of two phase 3 trials investigating KSI-101 for MESI, PEAK, and PINNACLE that are actively enrolling.”

The phase 1b trial, named APEX, enrolled patients with MESI who had active or nonactive non-infectious intraocular inflammation (either acute or chronic) with active leakage on fluorescein angiography, central subfield thickness (CST) greater than or equal to 320 μm, and BCVA of 20/32 or worse. The study investigated three doses of KSI-101—2.5, 5.0, or 10.0 mg. Patients received four injections of their assigned dose at monthly intervals and were followed to the end of the study at 24 weeks.

Enrolment in APEX included 41 patients. About two-thirds of patients had posterior inflammation, and about one-fourth had panuveitis. Baseline mean VA was approximately 20/50 (63.5 ETDRS letters), and mean CST was 493 μm. The interim analysis Dr Wykoff presented included data from 27 patients who had reached week 12 by 14 July 2025.

Functional assessments showed that BCVA increased from baseline by week 4. Across the three dose groups at week 12, mean BCVA gains from baseline ranged from 7.8 to 11.8 ETDRS letters, and 50% of patients had gained 15 letters or more.

Anatomic improvement occurred rapidly, with the majority of patients having resolution of intraretinal or subretinal fluid by week 1. At week 12, CST was 300 μm or less in all eyes and decreased by 199 to 237 microns across the three treatment groups; 100% of eyes had resolution of both intraretinal and subretinal fluid.

The safety review showed KSI-101 was safe and well-tolerated. There was a single case of vitreous haemorrhage, with this event occurring following anterior chamber paracentesis and before dosing of KSI-101. Intraocular inflammation occurred in two eyes and was attributed to underlying uveitis rather than KSI-101.

Dr Wykoff mentioned that a parallel arm of the phase 1b APEX trial is investigating KSI-101 in patients with diabetic macular oedema. This 24-week study enrolled 12 patients who received five monthly doses of KSI-101 in the same increments. Preliminary end-of-study results for these patients showed KSI-101 to be safe and well-tolerated with no cases of intraocular inflammation. From baseline to week 24, BCVA improved by a mean of 13.1 ETDRS letters. Mean CST was less than 325 μm by week 12 and remained stable through week 24, having decreased by an average of 175 μm from baseline.

Dr Wykoff spoke at EURETINA 2025 in Paris.

Charles C Wykoff MD, PhD is Deputy Chair of Ophthalmology, Blanton Eye Institute, Methodist Hospital and Director of Research, Retina Consultants of Texas, both of Houston, Texas, US. ccwmd@retinaconsultantstexas.com