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Writer's pictureRetina Global

Pegcetacoplan injection demonstrated increasing treatment effect over 3 years in AMD patients



Date from Apellis Pharmaceuticals' GALE extension study following 3 years of continuous treatment with SYFOVRE® (pegcetacoplan injection) demonstrates increasing treatment effects year-over-year and a more than 40% reduction in nonsubfoveal lesion growth in the third year.



In Year 3, the treatment:

  • Reduced GA lesion growth with both monthly (35%; p<0.0001) and every-other-month (24%; p<0.0001) treatment compared to the projected sham arm.

  • Reduced nonsubfoveal GA lesion growth with both monthly (42%; p<0.0001) and every-other-month (28%; p=0.0015) treatment compared to the projected sham arm.

  • Reduced GA lesion growth by 19% (p<0.0001) after one year of SYFOVRE treatment (combined monthly and every-other-month), compared to the sham treatment period, in patients who crossed over from the sham group.


An analysis of the untreated fellow eye further validated the treatment effects observed in Year 3. In patients with bilateral GA, lesions are known to grow at similar rates in both eyes. The fellow eye analysis serves as an important additional control to assess treatment effect.


The safety profile of the treatment in Year 3 remained consistent with previously reported data.


During the first year of GALE, the rate of new-onset investigator-reported exudative AMD was 7.1% (monthly) and 2.3% (every-other-month). There was one serious adverse event of ischemic optic neuropathy in the monthly group between Months 24 to 30, which was previously reported, and one case of endophthalmitis between Months 30 to 36. The rate of intraocular inflammation was 0.26% per injection from Months 0 to 36, which does not include the four cases linked to the 2018 impurity. Zero events of retinal vasculitis have been observed in the clinical trial program, following more than 24,000 injections to date.


Approximately 92% of patients enrolled in GALE completed the first year of the study, demonstrating robust long-term treatment compliance.


The GALE Long-Term Extension Study (n=792) is a Phase 3, multicenter, open-label, extension study to evaluate the long-term efficacy and safety of SYFOVRE® (pegcetacoplan injection) in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The objectives of the study are to evaluate the long-term incidence and severity of ocular and systemic treatment emergent adverse events as well as change in the total area of GA lesions as measured by fundus autofluorescence. More than 80-percent of participants who completed the OAKS and DERBY studies entered the GALE study. GALE also includes 10 patients who were previously enrolled in the Phase 1b study of pegcetacoplan for GA.


Patients included in the 3-year GALE lesion growth reduction analyses were in the SYFOVRE treatment arms through Month 24 in the OAKS and DERBY studies and remained on the same regimen in GALE. Sham-treated patients in the Phase 3 OAKS and DERBY studies were eligible to transition to SYFOVRE treatment in GALE after Month 24, so a projected sham arm was used to estimate the growth of GA lesions without treatment between Months 24 and 36. The projected sham arm was estimated as the average 12-month mean rate of change in the OAKS and DERBY sham arms through Month 24.


The Phase 3 OAKS (n=637) and DERBY (n=621) Studies were Phase 3, multicenter, randomized, double-masked, sham-controlled studies comparing the efficacy and safety of SYFOVRE® (pegcetacoplan injection) with sham injections across a broad and heterogenous population of patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The studies evaluated the efficacy of monthly and every-other-month SYFOVRE in patients with GA assessed by change in the total area of GA lesions from baseline as measured by fundus autofluorescence.


In Phase 3 studies at 24 months, both every-other-month and monthly SYFOVRE reduced GA lesion growth with increasing effects over time and showed a well-demonstrated safety profile.


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