Eat, Shoot or Drop?

The Injection to End All Injections

The standard of care for wet age-related macular degeneration (AMD) is regular intravitreal injections of anti-VEGF therapy. Unfortunately, although this is effective, the burden of frequent injections for patients and caregivers means that real-world visual acuity outcomes fall short of clinical trial results because of under-dosing. This disparity has led to a push in the retina field to develop sustained delivery strategies. For the first time, gene therapy has been applied as a mechanism for drug delivery with ADVM-022, which is designed to provide long-term anti-VEGF treatment (aflibercept) with a single intravitreal injection. “The results so far have been really positive, with efficacy shown 13 months post-injection, comparable to the standard of care,” says Szilard Kiss, Director of Clinical Research and Associate Professor of Ophthalmology at Weill Cornell Medical College, New York, USA (1). The drug was found to be safe and well-tolerated (inflammation could be managed with steroid eye drops), displaying consistent and sustained anatomical improvements on OCT, without the need for any rescue injections. “In the future, the plan is to further develop the treatment for diabetic retinopathy (DR) patients as well,” adds Kiss.

A Better Pill to Swallow

An oral AMD treatment could offer a number of benefits, including reduced visits to the clinic, increasing compliance, easier administration, and potentially even offering protection to the other eye.

AKST4290 is an orally administered treatment, which is currently in clinical trials for wet AMD. “Results are promising, with 83 percent of treatment-naïve patients and 72 percent of treatment-refractory patients showing maintenance or improvement of best corrected visual acuity (BCVA),” says Michael Stewart, Chairman of the Department of Ophthalmology and Professor of Ophthalmology at the Mayo Clinic in Jacksonville, USA. But compliance with oral medication is also an issue, and safety is a concern with any systemic medication – thankfully, the phase 2A trials have so far shown only mild adverse effects. Following the results of a phase 2B trial, the drug is planned to enter phase 3 clinical trials in 2020, with exploratory trials for DME and retinal vein occlusions also on the horizon.

A Drop a Day

A recent clinical study has suggested that a once-daily topical eye drop named PAN-90806 may make anti-VEGF therapy safe, less burdensome, and help patients avoid the frequent intravitreal injections required by current treatment regimes. It could also have a significant benefit in terms of patient adherence.

This is the first topical anti-VEGF eye drop to demonstrate both safety and biological response as a monotherapy in treatment-naïve patients with wet AMD. Over half of the clinical trial participants completed the study without the need for a rescue injection, and 88 percent of these experienced either clinical improvement or stability of their disease, supporting its continued clinical development (2).