Apellis Announces Detailed Results from Phase 3 DERBY and OAKS Studies Presented at Retina Society Annual Meeting
September 30, 2021
- Results further support the efficacy and safety profile of pegcetacoplan, an investigational, targeted C3 therapy, with monthly and every-other-month treatment
- Pegcetacoplan has the potential to become the first treatment for GA, a leading cause of blindness worldwide
WALTHAM, Mass., Sept. 30, 2021 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals, Inc. (Nasdaq: APLS), a global biopharmaceutical company and leader in complement, today announced that detailed data from the Phase 3 DERBY and OAKS studies were presented for the first time as part of two oral presentations at the Retina Society Annual Scientific Meeting in Chicago. The studies evaluated the efficacy and safety of pegcetacoplan, an investigational, targeted C3 therapy, in geographic atrophy (GA) secondary to age-related macular degeneration (AMD). GA is a leading cause of blindness that impacts more than five million people globally including one million people in the United States.1,2
In the OAKS study, monthly (p=0.0003) and every-other-month treatment (p=0.0052) with pegcetacoplan met the primary endpoint, significantly reducing GA lesion growth compared to pooled sham at 12 months. The DERBY study narrowly missed the primary endpoint, showing a reduction in GA lesion growth with monthly (p=0.0528) and every-other-month treatment (p=0.0750) compared to pooled sham at 12 months. In a prespecified analysis of the combined studies, pegcetacoplan showed a reduction in lesion growth in patients with foveal and extrafoveal lesions, with a greater effect in patients with extrafoveal lesions at baseline. Apellis plans to submit a New Drug Application (NDA) for pegcetacoplan for GA to the U.S. Food and Drug Administration (FDA) in the first half of 2022.
“The data presented at Retina Society reinforce that pegcetacoplan is a breakthrough for patients with GA, a relentless disease that leads to blindness and has no treatment,” said Charles Wykoff, M.D., Ph.D., investigator of the OAKS study and director of research, Retina Consultants of Texas. “Pegcetacoplan demonstrated a clinically meaningful treatment effect and favorable safety profile with both monthly and every-other-month dosing, highlighting the potential of pegcetacoplan to become the first treatment for GA.”
The presentations also included new analyses that evaluated the differences between the studies:
Reduction in GA lesion growth in U.S. vs rest of world (ROW) at 12 months
In a prespecified subgroup analysis of the primary endpoint, patients in the U.S. showed a consistent reduction in lesion growth with both monthly and every-other-month pegcetacoplan treatment compared to pooled sham at 12 months. The U.S. represents approximately two-thirds of the population in each study. The company continues to investigate the geographic differences in the ROW populations.
Evaluation of effect size by analyzing OAKS, DERBY, and Phase 2 FILLY studies adjusted for baseline imbalances
In order to better understand the effect size of pegcetacoplan, a post hoc analysis was conducted to adjust for imbalances in baseline characteristics known to be specifically associated with lesion growth. Results showed a consistent reduction in lesion growth compared to pooled sham across OAKS, DERBY, and FILLY with both monthly and every-other-month pegcetacoplan treatment at 12 months.
*The non-adjusted treatment rates in FILLY were measured using square root lesion size. When measured using the untransformed lesion size in FILLY, non-adjusted treatment rates were 31% with monthly and 21% with every-other-month treatment.
Pegcetacoplan demonstrated a favorable safety profile in both Phase 3 studies. The pooled rate of new-onset exudations was 6.0%, 4.1%, and 2.4% in the pegcetacoplan monthly, every-other-month, and sham groups, respectively. Rates of endophthalmitis and intraocular inflammation were generally in line with those reported in studies of other intravitreal therapies.
Detailed efficacy and safety data presented at the Retina Society Annual Scientific Meeting may be accessed on the company’s website.
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 at 12 months (p-value less than .05). Patients in DERBY and OAKS will continue on masked treatment for 24 months.
About Geographic Atrophy (GA)
GA is an advanced form of age-related macular degeneration (AMD), a leading cause of blindness. GA lesions affect the central portion of the retina, known as the macula, which is responsible for central vision. Excessive complement activation drives irreversible lesion growth in GA,3 and C3 is the only target to precisely control complement overactivation. GA is progressive and irreversible, leading to central visual impairment and permanent loss of vision. Based on published studies, more than five million people have GA globally including approximately one million people in the United States.1,2 There are currently no approved treatments for GA.
About Pegcetacoplan for Geographic Atrophy (GA)
Pegcetacoplan is an investigational, targeted C3 therapy designed to regulate excessive activation of the complement cascade, part of the body’s immune system, which can lead to the onset and progression of many serious diseases. Pegcetacoplan was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of geographic atrophy.
Apellis Pharmaceuticals, Inc. is a global biopharmaceutical company that is committed to leveraging courageous science, creativity, and compassion to deliver life-changing therapies. Leaders in targeted C3 therapies, we aim to develop transformative therapies for a broad range of debilitating diseases that are driven by excessive activation of the complement cascade, including those within hematology, ophthalmology, nephrology, and neurology. For more information, please visit http://apellis.com.
Apellis Forward-Looking Statement
Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to Apellis’ interpretation of results from the DERBY and OAKS trials, its planned timing of regulatory submissions and the potential advantages and therapeutic potential of intravitreal pegcetacoplan for GA. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: whether results obtained in preclinical studies and clinical trials will be indicative of results that will be generated in future clinical trials; whether the results of the DERBY and OAKS trials are sufficient to support regulatory submissions; whether a submission for approval of intravitreal pegcetacoplan for GA on the basis of the DERBY and OAKS trials will be accepted by the FDA or foreign regulatory agencies; whether intravitreal pegcetacoplan will receive approval from the FDA or equivalent foreign regulatory agencies for GA when expected or at all; whether, if intravitreal pegcetacoplan receives approval, it will be successfully distributed and marketed; and other factors discussed in the “Risk Factors” section of Apellis’ Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on August 9, 2021 and the risks described in other filings that Apellis may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Apellis specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.
1 Rudnicka AR, Jarrar Z, Wormald R, et al. Age and gender variations in age-related macular degeneration prevalence in populations of European ancestry: a meta analysis. Ophthalmology 2012;119:571–580.
2 Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health 2014;2:e106–116.
3 Seddon, JM, Rosner, B. Validated prediction models for macular degeneration progression and predictors of visual acuity loss identify high-risk individuals. Am J Ophthalmol 2019;198:223–261.