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A discussion into safety data from the Phase 3 DERBY and OAKS trials on pegcetacoplan with Dr. Boyer at AAO 2022.
Twenty-four month data from the DERBY and OAKS studies better indicate the overall safety of pegcetacoplan for geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
Pegcetacoplan is an investigational, targeted C3 therapy, studied in over 1200 patients between the two phase 3 studies. The safety data were presented at the 2022 American Academy of Ophthalmology Meeting in Chicago.
In an interview with HCPLive, presenting author David Boyer, MD, Senior Partner, Retina-Vitreous Associates Medical Group, discussed the observed safety signals and their connection to the greater benefit of the drug.
In terms of intraocular inflammation, most patients had mild to moderate forms and almost all patients were able to go back on treatment without sequelae, according to Boyer.
"I think that the inflammatory aspect needs to be evaluated in much larger studies, even though this was a huge study, but it seems to be very mild to moderate in 70% of the cases," Boyer said.
He added the risk of endophthalmitis with injection was low, at about 0.034% per injection compared to 0.03% with anti-VEGF injections in large databases.
Some inflammation was observed at the study start in 2018, when an impurity observed in the drug led to a study stop after four patients developed severe uveitis. Boyer noted it is unrelated to the present study drug, but they are still included in the analysis.
Another concern is the formation of wet macular degeneration, as observed in the phase 2 FILLY study. However, the inclusion criteria in DERBY and OAKS included patients with neovascularization in the other eye and could be receiving anti-VEGF treatment.
"You have patients that are more apt to get a choroidal neovascularization in the eye that's being treated because they're exposed and the other eye to have neovascularization," Boyer said. "Even with that, the numbers were low."
The results were approximately 12% of developing choroidal neovascularization in the monthly and 6.7% in the every other month groups, compared to only 3% in the sham group.
While these numbers were investigator determined, Boyer added that when patients were sent to a reading center, the numbers went down. However, he noted that to play it safe, the higher incidence in the trials should be considered first.
Patients whose other eye had wet AMD had more likelihood of neovascularization, but the reasoning is not fully understood, although it has been observed in other studies.
"It's interesting, it hardly ever caused any significant loss of vision and they were able to be treated successfully with anti-VEGF simultaneously," Boyer said. "They would maintain their vision. I think this is something that will come up more when we go out into practice and hopefully utilize this drug."
He additionally spoke to 3 cases of ischemic optic neuropathy with a lack of mechanism for understanding why it occurred. One patient was diabetic which predisposed them to greater risk and one had a severe case of hypertension.
However, investigators do not believe it was related to the study drug, but Boyer suggests it is something to keep an eye on in the future.
Other topics discussed by Boyer included the potential FDA approval for pegcetacoplan at the end of November, the promise of a GA drug on the patient-level, and if the innovations in the GA space will define the year in ophthalmology.
Check out other coverage from AAO 2022 here.