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  • Pegcetacoplan May Slow GA Progression

    By Lynda Seminara
    Selected By: Stephen D. McLeod, MD
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    Journal Highlights

    Ophthalmology, February 2020

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    Although efforts have been made to determine how complement activation pathways may affect the development and progression of age-related mac­ular degeneration (AMD), there is no treatment for geographic atrophy (GA) caused by AMD. Liao et al. investigated the effects of pegcetacoplan, a pegylated complement C3 inhibitor peptide, in patients with GA secondary to AMD. They found that this treatment signifi­cantly reduced the growth rate of GA lesions.

    For this prospective phase 2 study, the researchers enrolled 246 adults (≥50 years of age) with GA. They were assigned randomly (2:2:1:1) to receive either intravitreal injections of pegceta­coplan (15 mg) or sham injections, on either a monthly or every-other-month basis, for a 12-month period. Follow-up assessment occurred at months 15 and 18. Fundus autofluorescence imag­ing was used to evaluate GA area and growth. The main efficacy end point was mean change in square root of the lesion area from baseline to month 12. Safety end points included the number and severity of treatment-emergent adverse events.

    By 12 months, the lesion growth rate relative to sham injection was 29% slower with monthly pegcetacoplan (p = .008) and 20% slower with peg­cetacoplan every other month (EOM; p = .067). The effect of monthly or EOM pegcetacoplan was greater in the second six months of treat­ment (reductions of 45% and 33%, respectively). The lesions started growing when active treatment was stopped, suggest­ing the need for ongoing injections. Of note, new-onset exudative AMD was found more frequently in pegcetaco­plan-treated eyes (21% vs 9%). Other­wise, the drug’s safety profile resembled that of other intravitreal agents. The patients most prone to exudative AMD had a history of choroidal neovascular­ization in the fellow eye. Two cases of culture-positive endophthalmitis and one case of culture-negative endoph­thalmitis occurred in patients who received pegcetacoplan.

    According to the authors, their study shows the effectiveness of C3 inhibition in slowing GA progression. Both efficacy and safety were sufficiently favorable to warrant phase 3 studies.

    The original article can be found here.