Is ophthalmology entering its golden era? With the explosion of new biologics and biosimilars, novel imaging technologies, AI-enabled analytics, landmark clinical trials and major FDA approvals, the 2020s are shaping up to be quite a bright time for eye health.

In 2023, for instance, the FDA approved the first-ever drug for geographic atrophy — pegcetacoplan. Later in the year, the agency approved a second drug option (avacincaptad pegol) for the condition, an advanced form of age-related macular degeneration previously considered untreatable.

Pegcetacoplan, marketed as Syfovre, demonstrated promising results in two major trials — the OAKS and the DERBY — led in part by Dr. Charles Wykoff, a Houston Methodist ophthalmologist and retinal disease expert helping to drive much of the recent research renaissance.

"Geographic atrophy leads to a tremendous amount of vision loss and its impact can have substantial negative effects on patients and their families, with independence and quality of life severely impacted in many cases because of progressive difficulty with visual tasks including reading, driving, cooking, watching TV, recognizing faces and reading lips during conversation," Dr. Wykoff said. "While the drug does not reverse or stop progression, it can significantly slow the growth of lesions causing vision loss."

The OAKS and DERBY trials enrolled a total of 1,258 patients to assess the efficacy and safety of pegcetacoplan in slowing the growth of geographic atrophy over a two-year period. Both trials were global, multicenter, randomized, double-masked and sham-controlled.

The trials involved three groups: patients treated every month, patients treated every other month, and those receiving sham injections.

While the OAKS trial met its primary endpoint at one year, the DERBY trial did not. However, in both trials the key findings that led to FDA approval were an increase in effectiveness over time and significant slowing of the progression of geographic atrophy over a two-year period.

In combined study results, treatment with pegcetacoplan exhibited an increasing effect size over time, with a reduction in growth reaching 24% to 30% in the last six months, compared to 12% to 13% in the first six months.

"This is a truly exciting development, and we are looking forward to following these patients over the next several years to see if the drug continues to work better over time," Dr. Wykoff explained.

The extension study is the GALE study, which aims to assess OAKS and DERBY trial patients for a total of five years of continuous dosing. Dr. Wykoff noted that an impressive 83% of patients from the OAKS and DERBY trials transitioned to the GALE, and 92% of those have completed the first year of the extended trial.

Despite DERBY not meeting its primary endpoint at one year, the FDA acknowledged the increasing efficacy signal over time was the most crucial factor. Dr. Wykoff speculated on potential reasons for the discrepancy between the OAKS and DERBY, citing different clinical trial sites and patient populations.

Addressing the importance of functional endpoints, Dr. Wykoff noted that patients care more about improved vision than anatomical details. While predefined visual endpoints showed no statistically significant differences, microperimetry indicated potential benefits in preserving tissue and function with ongoing pegcetacoplan treatment.

Dr. Wykoff highlighted several important safety considerations. Within the trial program, there was a dose-dependent development of wet AMD as a meaningful side effect. In the monthly treatment group, 19.5% developed wet AMD compared to 8.6% in the every-other-month group after 36 months of continuous pegcetacoplan treatment. Other adverse events in the trials included ischemic optic neuropathy and intraocular inflammation. Since FDA approval, there have been rare reports of retinal vasculitis, retinal vascular occlusion and severe vision loss.

When asked about the potential link between pegcetacoplan and new-onset wet AMD, Dr. Wykoff acknowledged uncertainty and emphasized the importance of early diagnosis and appropriate management. Notably, patients who developed wet AMD during the trial responded well to anti-VEGF agents, which can be administered on the same day as pegcetacoplan.

The FDA approved Syfovre in February 2023 and avacincaptad pegol (Izervay) in August 2023.

A total of 87 retinal disease treatments, including 21 brand-new therapies, were in the clinical trial pipeline in 2023.