Apellis Announces Detailed 18-Month Results from Phase 3 DERBY and OAKS Studies of Pegcetacoplan for Geographic Atrophy (GA)

Apellis Pharmaceuticals announced detailed, longer-term data from the phase 3 DERBY and OAKS studies of intravitreal pegcetacoplan, an investigational, targeted C3 therapy, for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Monthly and every-other-month pegcetacoplan showed a continuous and clinically meaningful reduction in the growth of both extrafoveal and foveal lesions at month 18. The analysis was reported during an oral presentation at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting taking place May 1-4 in Denver and builds on the previously announced 18-month data.

“Slowing disease progression and preserving vision longer is critical for all patients with GA, so I am very encouraged that pegcetacoplan continuously reduced lesion growth over time in patients who are representative of the real-world GA population,” said Roger Goldberg, MD, presenting author and vitreoretinal specialist at Bay Area Retina Associates. “These results support that we are on the brink of the first potential treatment for patients living with this relentless, progressive, and irreversible disease.”

Pegcetacoplan Continues to Reduce GA Lesion Growth in Broad Patient Population at Month 18

In a longer-term analysis of the primary endpoint, pegcetacoplan continued to show a robust reduction in GA lesion growth in patients with extrafoveal lesions and an improved effect in patients with foveal lesions compared to pooled sham at month 18 (all p-values are nominal). GA typically presents first with extrafoveal lesions, which then progress toward the fovea where central vision is impacted.

• 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.”

At month 18, pegcetacoplan continued to demonstrate a favorable safety profile, consistent with safety rates at 12 months and longer-term exposure to intravitreal injections. The combined rate of new-onset exudations at month 18 was 9.5%, 6.2%, and 2.9% in the pegcetacoplan monthly, every-other-month, and sham groups, respectively. Rates of infectious endophthalmitis and intraocular inflammation continue to be consistent with those reported in studies of other intravitreal therapies.^1,2,3

These data will be included in the new drug application that the company plans to submit to the FDA in the second quarter of 2022.

Ten Presentations Showcase Apellis’s Leadership in Retina

Two oral presentations included an 18-month analysis from the phase 3 DERBY and OAKS studies that adjusted for imbalances in baseline characteristics known to be associated with lesion growth as well as results from a consensus survey on GA management.

Seven scientific presentations highlighted data from the pegcetacoplan clinical development program for GA, the disease burden, and use of artificial intelligence to identify, monitor, and predict GA lesion growth. Four of the artificial intelligence presentations were in collaboration with the Ophthalmic Image Analysis (OPTIMA) group at the Medical University of Vienna, one of the world’s leading data analysis laboratories for retinal diseases.

About DERBY and OAKS  

DERBY (621 patients enrolled) and OAKS (637 patients enrolled) are phase 3, multicenter, randomized, double-masked, sham-controlled studies comparing the efficacy and safety of intravitreal pegcetacoplan with sham injections in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The primary objective of the studies is to evaluate the efficacy of pegcetacoplan in patients with GA assessed by change in the total area of GA lesions from baseline as measured by fundus autofluorescence (p-value less than .05) at 12 months. Patients in DERBY and OAKS will continue to receive masked treatment for 24 months. Secondary functional endpoints will be evaluated after all patients have received treatment for 24 months.

The nominal p-values presented in the month 18 results were calculated using the same methodology as the month 12 primary endpoint analysis.