Apellis Announces 24-Month Phase 3 Post Hoc Results Showing Treatment with Pegcetacoplan Led to Preservation of Function in High-Risk Areas of the Retina in Patients with Geographic Atrophy (GA) at AAO Annual Meeting
Apellis Pharmaceuticals announced promising results from the 24-month Phase 3 OAKS study of pegcetacoplan for treating geographic atrophy (GA) related to age-related macular degeneration (AMD). New analyses revealed that patients receiving pegcetacoplan treatments, both monthly and every-other-month, exhibited improved visual function near GA lesion borders compared to sham treatments. The data supports pegcetacoplan's potential as the first effective therapy for GA, aiming for regulatory submissions to the European Medicines Agency and a PDUFA target action date of November 26, 2022, in the U.S.
- Positive trends in visual function preservation near GA lesion borders were observed with pegcetacoplan treatment.
- Pegcetacoplan is positioned to be the first treatment for GA, addressing a significant unmet medical need.
- Both monthly and EOM treatments showed reduced retinal sensitivity loss compared to sham over 24 months.
- Statistically significant differences were not observed between pegcetacoplan and sham for certain microperimetry measures due to broad retinal area assessments.
- The combined rate of new-onset exudations in pegcetacoplan groups (12.2% monthly; 6.7% EOM) reflects potential safety concerns.
- New analyses of microperimetry data showed positive trends with both monthly and every-other-month pegcetacoplan treatment near the GA lesion border compared to sham
- These analyses provide further evidence that slowing GA lesion growth with pegcetacoplan has the potential to preserve visual function
- Data were presented during an oral presentation at the American Academy of Ophthalmology Annual Meeting
WALTHAM, Mass., Sept. 30, 2022 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals, Inc. (Nasdaq: APLS), a global biopharmaceutical company and leader in complement, today announced new data from the 24-month Phase 3 OAKS study of pegcetacoplan, an investigational targeted C3 therapy, for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration.
Two post hoc analyses of microperimetry data showed positive trends with increasing effects over time, demonstrating both monthly and every-other-month (EOM) pegcetacoplan treatment preserved visual function of retinal cells near the GA lesion border compared to sham. These data were presented during an oral presentation at the American Academy of Ophthalmology (AAO) Annual Meeting.
“These results provide the first direct evidence that slowing GA lesion growth has the potential to preserve visual function,” said Charles Wykoff, M.D., Ph.D., presenting author and director of research, Retina Consultants of Texas. “There is a pressing need for a treatment for GA given the progressive, irreversible vision loss that severely impacts daily living for millions of patients. Combined, these data underscore the potential of pegcetacoplan to preserve vision over the long term and become the first treatment for GA.”
Lesion borders grow at approximately 100-150 microns per year1, and the analyses measured the visual function of cells within 250 microns on either side of the lesion border that are at the highest risk of permanently losing visual function as lesions expand. At 24 months, positive trends in microperimetry measures were demonstrated (all p-values nominal):
- Reduction of retinal sensitivity as measured by microperimetry reflects loss of function. Patients in both monthly (0.564 dB; p=0.0650) and every-other-month (EOM) (0.707 dB; p=0.0202) pegcetacoplan treatment groups lost less retinal sensitivity compared to the sham group over 24 months with increasing effects over time.
- Scotomatous points measure areas of the retina that have lost all light sensitivity and therefore are no longer functioning. Patients in both monthly (-0.680 points; p=0.1444) and EOM (-1.138 points; p=0.0140) pegcetacoplan treatment groups had fewer new scotomatous points compared to sham over 24 months with increasing effects over time.
A Media Snippet accompanying this announcement is available by clicking on the image or link below:
Microperimetry was a key secondary endpoint measured only in the OAKS study. Statistically significant differences on the prespecified endpoint were not observed between pegcetacoplan and sham given the large area of the retina assessed, which included areas that were farther away from the GA lesion and thus not at high risk of losing function due to GA lesion growth.
As previously reported, both monthly and EOM pegcetacoplan showed increased effects on slowing lesion growth over time, with an acceleration between months 18-24 (combined:
“Pegcetacoplan is the only treatment for GA to demonstrate increased effects on slowing lesion growth over time and a favorable safety profile in two large, Phase 3 studies,” said Federico Grossi, M.D., Ph.D., chief medical officer, Apellis. “We are excited these data are being shared across several oral presentations at AAO, which continue to highlight our leadership in retina and the breakthrough potential of pegcetacoplan.”
Pegcetacoplan demonstrated a favorable safety profile, consistent with safety data to date and longer-term exposure to intravitreal injections. Over 24 months, the rates of infectious endophthalmitis and intraocular inflammation were generally in line with reported rates in studies of other intravitreal therapies.2,3,4 The combined rate of new-onset exudations at month 24 was
The results will be included in the marketing authorization application that the company plans to submit to the European Medicines Agency by the end of this year. The U.S. marketing application is under Priority Review with a Prescription Drug User Fee Act (PDUFA) target action date of Nov. 26, 2022.
The presentation is available on the “Events and Presentations” page of the “Investors and Media” section of 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 (p-value less than .05) at 12 months. Patients in DERBY and OAKS received masked treatment for 24 months. All patients who completed the DERBY or OAKS studies were invited to participate in the GALE open-label extension study. The nominal p-values presented in the month 24 results were calculated using the same methodologies as the month 12 and 18 analyses.
About Geographic Atrophy (GA)
Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) and a leading cause of blindness that impacts more than 5 million people worldwide, including one million people in the United States.5,6 This progressive disease can severely impair visual function, independence, and quality of life as it takes on average 2.5 years for GA lesions to encroach the fovea, which is responsible for central vision.7 GA is caused by destruction of retinal cells through irreversible lesion growth that is driven by excessive complement activation.8 C3 is the only target that can precisely control the complement cascade due to its central location. 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.
About Apellis
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 complement, we ushered in the first new class of complement medicine in 15 years with the approval of the first and only targeted C3 therapy. We are advancing this science to continually develop transformative medicines for people living with rare, retinal, and neurological diseases. For more information, please visit http://apellis.com or follow us on Twitter and LinkedIn.
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 regarding timing of anticipated regulatory submissions. 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 the results of the FILLY, 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 FILLY, 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; and other factors discussed in the “Risk Factors” section of Apellis’ Annual Report on Form 10-K with the Securities and Exchange Commission on February 28, 2022 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.
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1Shen LL, Sun M, Grossetta Nardini HK, Del Priore LV. Progression of Unifocal versus Multifocal Geographic Atrophy in Age-Related Macular Degeneration: A Systematic Review and Meta-analysis. Ophthalmol Retina. 2020;4(9):899-910. doi:10.1016/j.oret.2020.03.020
2Morioka et al. Incidence of endophthalmitis after intravitreal injection of an anti-VEGF agent with or without topical antibiotics. Scientific Reports 2020.
3Kiss et al. Endophthalmitis rates among patients receiving intravitreal anti-VEGF injections: a USA claims analysis. Clin Ophthalmol 2018.
4Cox et al. Inflammatory complications of intravitreal anti-VEGF injections. Journal of Clinical Medicine 2021.
5Rudnicka 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.
6Wong 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.
7Lindblad AS, et al, and AREDS Research Group. Arch Ophthalmol. 2009;127(9):1168-1174.
8Seddon, 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.
FAQ
What are the results from the Phase 3 OAKS study on pegcetacoplan for GA?
When is the regulatory submission for pegcetacoplan expected?
How does pegcetacoplan impact visual function in GA patients?
