Prof Robyn Guymer ‘thrilled’ by Phase 3 results of pegcetacoplan for dry AMD

Prominent Melbourne retinal disease researcher Professor Robyn Guymer is encouraged by the Phase 3 results of a trial she’s been involved in, investigating a new therapy she says is the only intervention shown to significantly slow the growth of lesions in dry AMD.
The Centre for Eye Research Australia (CERA) deputy director and head of macular research is on the advisory board of Apellis Pharmaceuticals, a US-based company that is developing therapies for several debilitating diseases by controlling complement, part of the body’s immune system.
On 9 September, the company reported top-line results from the Phase 3 DERBY and OAKS studies evaluating intravitreal pegcetacoplan, an investigational targeted C3 therapy, in 1,258 adults with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The drug works to regulate excessive activation of the complement cascade.
In the OAKS trial, monthly and every-other-month treatment with pegcetacoplan met the primary endpoint, significantly reducing GA lesion growth by 22% and 16%, respectively, compared to pooled sham at 12 months.
DERBY did not meet the primary endpoint, showing a reduction in GA lesion growth of 12% and 11% with monthly and every-other-month treatment, respectively, compared to pooled sham at 12 months.
CERA was one of the recruiting sites for the trials, which recruited four patients into DERBY. Guymer was the principal investigator on the CERA trial but during a sabbatical in 2020 Dr Sanjeewa Wickremasinghe took over this role
Overall, there were 45 patients from Australia and New Zealand recruited into DERBY (nine) and OAKS (36). For DERBY, there were three sites in Australia (including CERA) and two in New Zealand, while for OAKS there were six centres in Australia and one in New Zealand.
 “I was thrilled to see that the DERBY and OAKS 12 month results produced the results that were anticipated from the Phase 2 trial,” Guymer said.
“Pegcetacoplan is currently the only intervention that has shown significant slowing of the growth of lesions in dry AMD. This is exciting news for all those patients that have been diagnosed with AMD.
In a statement to Insight, Apellis stated: “[We] plan to discuss the results with regulatory authorities worldwide, including the Therapeutic Goods Administration (TGA) in Australia. Our goal is to bring pegcetacoplan to patients with geographic atrophy as quickly as possible.”
Decades of work come to fruition
In other results, a prespecified analysis of the primary endpoint showed pegcetacoplan had a greater effect in patients with extrafoveal lesions at baseline.
Patients with GA typically present first with extrafoveal lesions, which then progress toward the fovea where central vision is impacted. In the combined studies, monthly and every-other-month treatment with pegcetacoplan decreased GA lesion growth by 26% and 23%, respectively, in patients with extrafoveal lesions compared to pooled sham at 12 months. 
Based on results, Apellis plans to submit a New Drug Application for pegcetacoplan for GA to the US Food and Drug Administration (FDA) in the first half of 2022.
“These results underscore the potential for pegcetacoplan to become the first treatment for geographic atrophy, a progressive and irreversible disease that robs patients of their vision and for which no treatment exists,” said Dr Jeffrey Heier, principal investigator of the DERBY study and director.
“Pegcetacoplan demonstrated a clinically meaningful slowing of disease progression with an even stronger effect in GA patients with extrafoveal lesions.”
Apellis chief medical officer Dr Federico Grossi said the company wanted to develop therapies for people with complement-driven diseases and now, after decades of challenges in such a complex disease, pegcetacoplan is the first investigational therapy to significantly slow the progression of GA in a large Phase 3 study.
“Across our ophthalmology development program, pegcetacoplan has demonstrated an efficacy and safety profile with both monthly and every-other-month dosing that we believe supports treatment for GA patients. We look forward to working with regulatory authorities to bring this medicine to patients in need as quickly as possible,” he said.
Pegcetacoplan was well tolerated in both Phase 3 studies. The pooled rate of new-onset exudations was 6.0% of patients in the monthly pegcetacoplan groups, 4.1% in the every-other-month pegcetacoplan groups, and 2.4% in the sham groups.
Two cases of confirmed infectious endophthalmitis and one case of suspected infectious endophthalmitis were observed in the study eye out of a total of 6,331 injections (0.047%).
Thirteen events of intraocular inflammation were observed in the studies (0.21% per injection). No events of retinal vasculitis or retinal vein occlusion were observed. There were no clinically relevant changes in vision for patients who developed infectious endophthalmitis or intraocular inflammation.
“On the heels of our recent FDA approval in paroxysmal nocturnal hemoglobinuria (blood disease), these pivotal results further reinforce the platform potential of targeting C3 across multiple diseases with few or no treatments,” said Dr Cedric Francois, Apellis co-founder and CEO.
“Apellis is singularly positioned to make a meaningful difference for patients living with a broad range of retinal, rare, and neurological diseases by targeting C3 to comprehensively control complement.”

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