Abstract
Purpose :
An ongoing Phase 1b clinical trial (NCT03790852), has demonstrated promising initial safety, efficacy and durability of repeated intravitreal injections of KSI-301, a novel anti-VEGF antibody biopolymer conjugate designed for improved intraocular durability, in patients with wet age-related macular degeneration (wAMD), diabetic macular edema/diabetic retinopathy (DME/DR) and retinal vein occlusion (RVO). In this paper, data with extended patient follow-up beyond 20 weeks and following multiple re-treatments over time will be reported.
Methods :
This is a multicenter, randomized, open-label, Phase 1b study in treatment-naïve subjects with wAMD, DME/DR or RVO followed over 72 weeks. Patients receive 3 initial monthly doses of either 2.5 mg or 5 mg of KSI-301 with additional treatment given according to disease-specific, protocol-specified retreatment criteria. Preliminary results for patients that have reached Week 20 (n=55) as of November 8, 2019 are presented in this abstract. Updated results beyond Week 20 will be provided at the meeting.
Results :
The phase 1b study is on-going, with 109 patients recruited across all three cohorts. Ocular safety of KSI-301 is encouraging with no reports of intraocular inflammation and no drug-related adverse events after 338 doses. Mean change in BCVA at Week 20 was +4.3 letters in wAMD (n=25, baseline 64.5), +7.4 letters in DME (n=15, baseline 66.8) and +21.3 letters in RVO (n=15, baseline 54.9). Mean change in CST was -67 microns (µm) in wAMD (baseline 426), -129 µm in DME (baseline 449) and -365 µm in RVO (baseline 675). 92% of wAMD eyes have been extended to 3 months or longer after the last loading dose without receiving retreatment. In DME 72% of DME eyes have been extended to four months or longer, and half of RVO eyes have been extended to 3 months or longer. New data with longer follow-up, with many patients followed beyond Week 20, will be presented for the first time at the meeting.
Conclusions :
Ongoing results of the Phase 1b study demonstrate that KSI-301 provides strong functional and anatomical outcomes with an excellent safety profile and remarkable biological durability. Recruitment of a pivotal study in wAMD comparing KSI-301 every 3-5 months vs aflibercept every 2 months is underway.
This is a 2020 ARVO Annual Meeting abstract.