Angiogenesis 2023: The tides of AMD reversed with drug targeting mitochondria to improve photopic vision

Investigators found risuteganib (Allegro Ophthalmics) improved the photopic best-corrected visual acuity (BCVA) by stabilizing the mitochondria.

Investigators, led by first author Baruch Kupperman, MD, PhD, reported that reversing visualloss in dry age-related macular degeneration (AMD) is possible with therapy that improves cellular function and survival, by targeting the mitochondria, in a patient population with a recoverable photoreceptor layer. They found that risuteganib (Luminate, Allegro Ophthalmics, LLC) improved the photopic best-corrected visual acuity (BCVA) by stabilizing the mitochondria.

Luminate is an investigational drug not yet approved by the FDA.

Dr. Kupperman, Roger F. Steinert professor, chair of the Department of Ophthalmology, and director of the Gavin Herbert Eye Institute at the University of California, Irvine, reported the findings at the Angiogenesis, Exudation, and Degeneration 2023 meeting at Bascom Palmer Eye Institute, Miami. He shared clinical evidence and considerations for matching the mechanism of action with the right patient population and stage of disease to reverse vision loss in dry AMD, which affects more than 15 million patients in the US.

He said, “Existing data suggest that restoration of functional vision is achievable in dry AMD patients with more anatomical integrity, or less disease progression, using these mitochondrial stabilizing drug candidates. This underscores the potential for early treatment of dry AMD, with the right therapeutic agent, to reverse vision loss.”

In their prospective, randomized, controlled trial, the researchers evaluated risuteganib for safety and effectiveness in patients with dry AMD (40) eyes, all of which had intermediate disease. They also sought to identify biomarkers that may predict a response to the risuteganib.

The study patients had BCVAs that ranged from 20/40 to 20/200 and were randomized to either active treatment or sham and followed for 32 weeks.

The primary study endpoint was the percentage of patients with an improvement of 8 or more letters, and the secondary endpoint was the percentage with an improvement of 10 and 15 letters improvement in the BCVA. The exploratory endpoints were changes in microperimetry, color vision, and anatomic changes seen on optical coherence tomography (OCT).

Results with risuteganib

The results showed that risuteganib caused substantial improvements in the BCVA compared with the results in the sham-treated patients.

The investigators found that 48%, 32% and 20% of the patients treated with risuteganib had improvements of 8 or more, 10, and 15 letters, respectively, compared with 7%, 7% , and 0% of the sham-treated patients. 

The authors commented that the BCVA improvements were “correlated strongly” with improvements in microperimetry and color vision.

A strong biomarker of the response to risuteganib was the baseline thickness of the ellipsoidal zone-retinal pigment epithelial layer. The results showed that 83% of those who responded to risuteganib and had a letter improvement of 8 or more letters had an ellipsoidal zone-retinal pigment epithelial layer that was 30 microns or thicker. This is in contrast to 38% of the non-responders.

No detectable anatomic changes were seen on OCT images over the course of the study. No drug-related serious adverse events were reported.

The investigators pointed out, “Intervention is most fruitful during the earlier stage of the disease, when patients have discernible visual function loss (such as the loss of reading, driving, cooking vision), but before complete atrophy of the retinal pigment epithelium and outer retina layers.”