Integrin Peptide Therapy: The First Wet AMD Experience

Abstract

Purpose: ALG-1001 is a synthetic anti-integrin oligopeptide. ALG-1001 inhibits integrin receptors in vitro and arrests aberrant blood vessel growth in vivo meditated by integrins αvβ3, αvβ5, and α5β1 - sites that are expressed in neovascular ocular tissue in wet AMD and diabetic retinopathy. ALG-1001 has demonstrated a statistically significant reduction in CNV, ROP, and vascular permeability in mouse models conducted by Dr. Peter Campochiaro. A 15 subject human phase 1 DME study demonstrated nearly 55% of the study subjects improving 3 lines or more in BCVA with at least a 30% reduction in OCT CMT with ALG-1001 mono-therapy. The purpose of this study is to evaluate the safety and dose ranging of intravitreal ALG-1001 in subjects with CNV due to wet AMD with a primary endpoint of observing for any dose limiting toxicity.

Methods: Key inclusion criteria included: Baseline BCVA between 20/50 and 20/320 and CNV due to AMD with no previous anti-VEGF treatment within 45 days of enrollment. A combination of treatment naïve and previously treated subjects were enrolled. All patients received a loading dose of 3 monthly intravitreal injections of either 1.5mg, 2.5mg, or 4.0mg ALG-1001 and were followed for an additional 4 months off treatment. Safety measurements included BCVA, slit lamp, fundus exam, IOP, OCT, FA, and fundus photos.

Results: To date, 15 subjects with neovascular AMD have been enrolled in this ongoing open label safety study. There have been no SAEs reported to date. AEs have primarily been limited to injection related events. While this is an ongoing study with 15 subjects enrolled to date, there are already clear improvements in BCVA and macular anatomy by OCT in this mono-therapy study in approximately 40% of the study subjects with clinical benefits lasting at least 60 days off treatment after a 3 monthly injection loading dose.

Conclusions: This was the first clinical trial of ALG-1001 in wet AMD and the first clinical study evaluating the dose ranging safety in human subjects. To date, there has been consistency in the lack of toxicity across all study metrics at doses up to 4.0 mg. Despite the small study size and open-label monotherapy dosing regimen, clinically relevant indicators of efficacy are apparent with improvements in BCVA alongside anatomic improvements in OCT CMT that persist at least 60 days past the last intravitreal treatment. Further studies will evaluate the further efficacy of this therapy.

Keywords: 700 retinal neovascularization • 453 choroid: neovascularization • 466 clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials