DERBY and OAKS: 18-month data shows continuous reduction in foveal, extrafoveal lesion growth in eyes with GA

At 2022 Association for Research in Vision and Ophthalmology (ARVO) annual meeting, Apellis unveiled the 18-month data from the Phase 3 DERBY and OAKS studies of intravitreal pegcetacoplan, revealing that monthly and every-other-month pegcetacoplan reduced the growth of extrafoveal and foveal lesions continuously up to month 18. The combined rate of new-onset exudations at month 18 was 9.5%, 6.2%, and 2.9% in the monthly, every-other-month, and sham arms, respectively. The data presented at ARVO demonstrates the potential of pegcetacoplan to slow the progression of GA in all cases, regardless of severity.

“Hope is on the horizon for our patients with this debilitating disease: the 18-month results of Derby and Oaks showed continued impact of pegcetacoplan to slow the growth of geographic atrophy,” said Roger Goldberg, MD, presenting author and vitreoretinal specialist at Bay Area Retina Associates. “The growth curves continue to separate over time, meaning more preserved retinal tissue with ongoing therapy. Safety-wise, the rates of exudation and inflammation remained low and in-line with the 12-month data. The prospect of slowing disease and potentially preserving vision longer for our patients is exciting.

Pegcetacoplan is an investigational, targeted C3 therapy for the treatment of geographic atrophy (GA). The C3 therapy is designed to regulate excessive activation of the complement cascade, which is part of the body’s immune system, to limit the onset and progression of disease. GA is an advanced form of dry age-related macular degeneration (AMD). With over 5 million people affected worldwide, it is a global leading cause of blindness. There is currently no approved therapy for GA. Apellis received Fast Track designation by the FDA in 2018 and is on track to submit a New Drug Application (NDA) for pegcetacoplan in the first half of 2022.

Through month 18 of Phase 3 studies OAKS and DERBY, pegcetacoplan remained consistent with safety rates at 12 months and long-term exposure to intravitreal injections, continuing to demonstrate a favorable safety profile. Infectious endophthalmitis and intraocular inflammation rates remained comparable to studies of other intravitreal therapies.

Data takeaways from the 18-month data from Phase 3 DERBY and OAKS (nominal P-values presented at month 18 were calculated using the same methodology as the 12-month primary endpoint analysis):

• Pegcetacoplan reduced extrafoveal GA lesion growth in OAKS by 33% (P < 0.0001) and 17% (P = 0.0422) with both monthly and every-other-month treatment, respectively, and in DERBY by 17% (P = 0.0606) and 23% (P = 0.0075), respectively.
• Pegcetacoplan reduced foveal GA lesion growth in OAKS by 18% (P = 0.0105) and 19% (P = 0.0020) with both monthly and every-other-month treatment, respectively, and in DERBY by 9% (P = 0.2015) and 4% (P = 0.5538), respectively.
• In the combined studies, pegcetacoplan reduced extrafoveal GA lesion growth by 26% (P < 0.0001) and 21% (P = 0.0006) with both monthly and every-other-month treatment, respectively, and reduced foveal lesion growth by 13% (P = 0.0070) and 13% (P = 0.0069), respectively.

“We are excited to see that longer-term use of monthly and every-other-month pegcetacoplan reinforces the potential for our targeted C3 therapy to slow GA progression regardless of disease severity,” said Federico Grossi, MD, PhD, chief medical officer at Apellis. “There is a significant need for GA treatments, so we look forward to working closely with regulatory authorities to bring pegcetacoplan as quickly as possible to patients around the world.”

In addition to the 18-month results DERBY and OAKS oral presentation, 6 additional presentations at ARVO highlighted data regarding the pegcetacoplan clinical development program for GA. The topics ranged from artificial intelligence to identify, monitor and predict GA lesion growth to disease burden for the patients. Artificial intelligence presentations were developed with Ophthalmic Image Analysis (OPTIMA) group at the Medical University of Vienna.

About DERBY and OAKS

Intended to evaluate the efficacy and safety of pegcetacoplan in patients with GA secondary to AMD, DERBY (621 participants) and OAKS (637 participants) are Phase 3, multicenter, randomized, double-masked, sham-controlled studies. The comparative studies pit intravitreal pegcetacoplan against sham injections with a primary objective to assess the efficacy of the targeted C3 therapy, which is measured by change in total area of GA lesions from baseline as measured by fundus autofluorescence (P-value less than .05) at 12 months. Enrolled patients will continue to receive masked treatment for 24 months, at which time the secondary functional endpoints will be evaluated.

About Apellis

Apellis Pharmaceuticals is a global biopharmaceutical company that is establishing leadership in geographic atrophy research. They hope for their investigational candidate, pegcetacoplan, to be the first FDA-approved therapy for advanced dry AMD.