KSI-301 Improves Wet AMD, Diabetic Macular Edema, and Retinal Vein Occlusion

Charles Wykoff, MD, PhD

Phase 1/1b studies examining novel intravitreal anti-VEGF therapy, with the potential to treat a multitude of retinal diseases, has returned positive results—a sign a new treatment could be on the horizon.

Interim results revealed KSI-301 improved visual acuity and was well-tolerated in patients with diabetic macular edema(DME), wet age-related macular degeneration(AMD), and retinal vein occlusion(RVO).

Presented at the American Academy of Ophthalmology (AAO) 2019 Annual Meeting in San Francisco by Charles Wykoff, MD, PhD, retina surgeon at Retina Consultants of Houston, results highlighted the potential of the novel antibody biopolymer conjugate.

A total of 105 patients were included in the randomized, open label phase 1b study, of which 35 had wet AMD, 35 had DME, and 35 had RVO. These patients were randomized in a 1:3 ratio to receive either a 2.5 mg or 5 mg dose of KSI-301.

The study was designed with an 8-week loading phase followed by a durability assessment phase that lasted from week 12 until week 36. Patients received injections at weeks 0, 4, and 8. Investigators noted patients were evaluated every 4 weeks during the durability assessment phase and could receive re-treatment as needed, except during week 36.

From baseline to week 16, a pooled analysis of patients with wet AMD detailed a mean gain in BCVA of 5.4 ETDRS letters. In terms of central subfield thickness(CST) measured by OCT, investigators observed a mean reduction of 72 microns. Wykoff noted only 8 instances of re-treatment had occurred in that group so far.

In patients with RVO, a pooled analysis revealed patients receiving KSI-301 experienced a mean gain in BCVA of 21.3 ETDRS letters and a mean reduction in OCT CST of 353 at week 16. Wykoff added 56% of patients have gone longer than 3 months after last loading dose.

Wykoff also highlighted phase 1a results that revealed KSI-301 resulted in rapid anatomic and visual response in patients with DME. Among patients who received KSI-301, the mean gain in BCVA at 30 days was 12.5 ETDRS letters and at 90 days the mean increase was 9 letters. Use also resulted in a mean reduction of 120 microns in OCT CST at 30 days.

In regard to safety, Wykoff pointed out there was zero cases of intraocular inflammation after more than 300 doses. Additionally, he added the phase 1b study had been extended to 18 months to further assess durability outcomes and a phase 2 study called DAZZLE has begun enrollment.

“KSI-301 has already entered into a pivotal phase 2 trial—DAZZLE. In which, 400 treatment-naive wet AMD eyes are being randomized to aflibercept versus KSI-301. In this trial KSI-301 is being dosed every 12, 16, or even every 20 weeks,” Wykoff said.

This study, “Extended Durability in Exudative Retinal Diseases Using the Novel Intravitreal Anti-VEGF Antibody Biopolymer Conjugate KSI-301: Results From the Phase 1b Study in Patients with wAMD, DME and RVO,” was presented by Charles Wykoff, MD, at AAO 2019.