Pegcetacoplan effective in controlling geographic atrophy in AMD patients
Intravitreal pegcetacoplan significantly reduced geographic atrophy progression in patients with age-related macular degeneration, according to a study published in the American Journal of Ophthalmology.
“Numerous interventions targeting [geographic atrophy (GA)] secondary to AMD have been tested in clinical trials with limited success,” Nathan C. Steinle, MD, of California Retina Consultants, and colleagues wrote. “Recently, treatment with pegcetacoplan was demonstrated to slow GA progression in a large phase 2 trial.”
Investigators further explored these findings by conducting an analysis of a prospective, multicenter, randomized trial that assessed the safety, tolerability and efficacy of IV pegcetacoplan in patients with GA secondary to AMD. The primary endpoint was change in GA lesion size from baseline to 12 months using fundus autofluorescence imaging.
A total of 246 participants, aged older than 50 years, were divided into four groups and received 15 mg pegcetacoplan monthly, 15 mg pegcetacoplan every other month (EOM), sham injection monthly or sham injection every other month for 12 months. Of those randomized patients, 176 were included in the final analysis, which considered the effects of age; gender; lesion size, focality and location; pseudodrusen status; best-corrected vision acuity; and low-luminance deficit (LLD) on GA progression.
According to study results, overall mean change in lesion size was 0.26 mm (P < .01), 0.27 mm (P < .05) and 0.36 mm in the monthly pegcetacoplan (n = 67), EOM pegcetacoplan (n = 58) and sham (n = 67) groups, respectively. In univariate analysis, patients with extrafoveal lesions (P < .001), BCVA greater than or equal to 20/60 (P = .001) and larger LLD (P = .002) had greater mean changes in lesion size.
Most patients in the analysis were women, and those who received sham injections had a higher rate of GA progression. No specific trend was observed in the male subgroup. Although approximately two-thirds of patients had multifocal lesions, those in in the pegcetacoplan treatment groups experienced lower GA growth rates regardless of lesion focality (unifocal or multifocal).
“Extrafoveal lesions and larger LLD are potential risk factors for GA progression,” Steinle and colleagues wrote. “Pegcetacoplan treatment significantly controlled GA progression even after accounting for these risk factors.”
Perspective
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There are currently no approved therapies to prevent the development or progression of GA in AMD patients. Even Age-Related Eye Disease Study-recommended supplementation, although often recommended to reduce the risk of developing neovascularization, has no beneficial effect on GA progression. Researchers hope to address this unmet medical need utilizing complement inhibitors.
In the phase 2 FILLY trial, pegcetacoplan, a complement C3 inhibitor peptide, demonstrated reduction in the growth of GA lesions compared to sham. An exploratory post-hoc analysis identified extrafoveal GA lesion (vs. foveal) and a larger low-luminance deficit (the decrease in visual acuity when the acuity chart is viewed through a 2.0-log unit neutral density filter) as baseline characteristics that are potential risk factors for GA progression. Encouragingly, pegcetacoplan treatment controlled GA progression even after accounting for these risk factors.
This is exciting data. However, pegcetacoplan did not halt GA progression entirely, and the original study highlighted a possible association between exudation and pegcetacoplan. I will reserve judgment until after the phase 3 trials. Understanding risk factors for GA progression, while important for patient education, will not change my current clinical practice until there is an approved treatment for the disease. Additionally, the post-hoc analysis is limited by small sample sizes.
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