Integrin Peptide Therapy: A New Class of Treatment for Vascular Eye Diseases - The First Human Experience in DME

Abstract

Purpose: : ALG-1001 is a synthetic anti-integrin oligopeptide. This is the first human clincal safety and efficacy data presented on this new class of anti-angiogenic compounds in the eye. Studies to date show that ALG-1001 inhibits integrin receptors in vitro and arrests aberrant blood vessel growth in vivo meditated by αvβ3, αvβ5 as well as α2β1 and α5β1 - integrin sites that are expressed in neovascular ocular tissue from patients with wet AMD and diabetic retinopathy. ALG-1001 demonstrated a statistically significant reduction in a CNV mouse model conducted by Dr. Peter Campochiaro.

Methods: : The objective was to evaluate the safety of intravitreal ALG-1001 in humans with end stage DME with a primary endpoint of observing dose limiting toxicity.15 patients with end-stage DME completed this open label study. Baseline BCVA was ≥ 20/100 & patients had not undergone anti-VEGF treatment or focal laser within 90 days -- many refractory to Avastin and previous photocoagulation. 3 monthly intravitreal injections of 2.5mg ALG-1001 were given, following subjects for an additional 3 months. Safety measurements included BCVA, slit lamp evaluation, fundus exam, IOP measurements, OCT, FA, fundus photos, B-scan, and ERG.

Results: : There were no Serious Adverse Events or Adverse Events with no inflammatory reactions or sustained elevations in IOP. There was clearly a clinically significant effect demonstrated. 8 of 15 subjects reported a 3 line or more increase in BCVA after receiving 3 injections with up to a corresponding 83% reduction in central macular thickness on OCT. The clinical benefit lasted at least 90 days off treatment to the end of the study. The non-responders did not experience any loss in BCVA from baseline or an increase in OCT central macular thickness over 5 months.

Conclusions: : This was the first human exposure to ALG-1001. The study objective was evaluating safety in human subjects. There was consistency in the lack of toxicity across all study metrics. Overall, ALG-1001 was very well tolerated. Despite the small study size, there has been a clinically significant indicator of efficacy with improvements in BCVA tracking anatomic improvements in OCT central macular thickness. The clinical improvements endured to the end of the study at least 90 days past the last intravitreal treatment in nearly all study subjects that demonstrated improvements.

Clinical Trial: : http://www.clinicaltrials.gov NCT01482871

Keywords: edema • macula/fovea • diabetic retinopathy