Justis Ehlers, MD, FASR | Image Credit: American Society of Retina Specialists

A single intravitreal dose of PER-001, a first-in-class, sustained-release intravitreal implant delivering an endothelin A receptor antagonist, has proven itself safe and well-tolerated, resulting in durable structural and functional improvements in patients with diabetic retinopathy (DR).1

These data, presented at the 43rd Annual Scientific Meeting of the American Society of Retina Specialists in Long Beach, CA, by Justis Ehlers, MD, FASR, Cole Eye Institute of the Cleveland Clinic, these data are the result of a phase 2a multicenter, randomized, sham-controlled, patient- and reading center-masked study. Ehlers and colleagues investigated patients with non-proliferative DR without center-involved diabetic macular edema (DME).1

With intravitreal implant treatments on the rise in ophthalmology, studies have presented a variety of potential medications and housing implants for several ocular diseases. Recently, dexamethasone implants have proven efficacy in treating patients with DME, paving the way for further research into alternative treatments to expand the regimen.2

During the trial, patients were randomized to receive either a single intravitreal injection of PER-001 on day 1 of low dose, high dose, or sham control, followed monthly for 6 months. Investigators monitored safety outcomes including best-corrected visual acuity (BCVA), intraocular pressure (IOP), biomicroscopy, and ocular and systemic adverse events (AEs). They utilized exploratory structural imaging, including ultra-widefield color fundus photography (UWCFP), spectral-domain optical coherence tomography (OCT), ultra-widefield fluorescein angiography (UWFA), and OCT angiography.1

UWFA analyses of vascular diseases included quantification of vascular leakage, macular ischemia, and macular microaneurysm count. Exploratory functional assessments also included contrast sensitivity, measured by the AST Manifold device and peripheral visual field using Humphrey Matrix perimetry. Investigators also noted key contrast sensitivity endpoints, which included low luminance sensitivity, low luminance, and low contrast visual acuity (LLLC-VA). These were chosen to capture real-world visual impairment reported in cases of DR.1

Investigators indicated that PER-001 was well tolerated, exhibiting no drug-related serious AEs. The only 2 AEs during the study were both reports of mild, intermittent vitreous floaters. No retinal vasculitis, intraocular inflammation, or endophthalmitis was reported. BCVA and IOP also remained stable over the course of 6 months.1

In regard to structural outcomes, PER-001 treatment led to improvements in UWFA evaluation of macular ischemia, vascular leakage, and microaneurysm count at months 3 and 6 compared to control. The macular ischemia index showed a reduction from baseline in the high- and low-dose groups at month 3 (-.51% to -.11%) and month 6 (-.22% and -.1%). The control group displayed an increase of +.6% and +.92%, respectively.1

Vascular leakage was reduced in the high-dose group at month 3 (-5.44%) and month 6 (-2.35%). The low-dose group, however, had a reduction at month 3 (-1.28) and an increase at month 6 ((+.82%). Notably, the control group exhibited greater worsening at both timepoints (+2.55% and +4.29%, respectively). Macular microaneurysm count saw a decrease from baseline of -6.63 and -3.57 at month 3 and a decrease of -7.5 and -7.86 at month 6 were observed for the high and low dose, respectively. The control group saw an increase from baseline of +12.86 and +5.6 at months 3 and 6, respectively.1

Investigators also noted the functional outcome, showing LLCS improved by +.89 dB and +.65 dB in the high- and low-dose groups, respectively, at month 5. The control group exhibited a decline of -2.1 dB, with a difference from control of +2.99 dB in the high-dose group and +2.75 dB in the low-dose group. LLLC-VA was better by a mean difference of 5.5 and 5.1 letters from baseline in both low and high dose groups, compared to control at week 20. Subjects that had reduced peripheral vision at baseline also demonstrated a +1.8 dB/year improvement in the PER-001 treatment groups compared to +.01 dB/year in control.1

“These findings support PER-001 as a first-in-class, disease-modifying therapy targeting the underlying neurovascular pathology with vision benefits in DR,” Ehlers and colleagues wrote. “PER-001 offers a promising approach for DR and other ischemic retinal diseases.”1

References