A brief clinical update reporting on a new anti-VEGF antibody conjugate polymer (identified as KSI-301) has highlighted visual acuity gains with three indications – wet AMD, diabetic edema and retinal vein occlusion. The experimental treatment has a novel higher molecular weight antibody moiety -950kDA- considerably larger than other anti-VEGF antibodies (ranibizumab [48kDa] and aflibercept [115kDa]). Preliminary research results from the study suggested that the new engineered polymer may increase durability and aims to develop a new first-line agent, potentially to enable earlier treatment and prevention of vision loss for patients with diabetic eye disease. The Phase 1/1b study is entitled: “Open label, multi-center exploratory study to investigate the bioactivity, ocular and systemic safety, tolerability, and pharmacokinetics following single and multiple intravitreal administrations of KSI-301 in subjects with wet age-related macular degeneration (wAMD), diabetic macular edema (DME) and retinal vein occlusion (RVO)”.
The randomised interventional clinical trial recruited 105 patients for testing intravitreal injections of two doses – 2.5mg and 5.0mg for the anti-VEGF (KSI-301). The Phase 1b was an open-label study of treatment-naive patients with wet age-related macular degeneration, diabetic macular edema/diabetic retinopathy or retinal vein occlusion randomized 1:3 to receive either one or other dose for KSI-301. Patients received three initial injections 4 weeks apart and were evaluated for the need for additional doses at 4-week intervals beginning at week 16. The initial results indicated that twenty-five wet AMD patients demonstrated a best corrected visual acuity (BCVA) letter gain of 5.4 letters and a 72 µm central subfield thickness (CST) improvement from baseline; twelve DME patients experienced an 8.4 BCVA letter gain and a 140 µm CST improvement from baseline, and; finally, fifteen RVO patients experienced a 21.3 BCVA letter gain and a 353 µm CST improvement from baseline. In addition to the report, there was zero cases of intraocular inflammation after more than 300 doses. The phase 1b study may be extended to 18 months to further assess durability outcomes and a Phase 2 study has now initiated enrolment.
Commenting of the results, Dr. Charles C Wykoff, M.D., Ph.D., Retinal Consultants, Houston, one of the investigators, stated that KSI-301 has already entered into a pivotal phase 2 trial—DAZZLE and now suggested that “400 treatment-naive wet AMD eyes are being randomized to aflibercept versus KSI-301, dosed every 12, 16, or even every 20 weeks.