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

Rhea-AI Summary

Apellis Pharmaceuticals (APLS) reported promising long-term results from the Phase 3 DERBY and OAKS studies for pegcetacoplan, a targeted C3 therapy, showing significant reductions in geographic atrophy (GA) lesion growth after 18 months.

Monthly and every-other-month treatments led to reductions of up to 33% for extrafoveal lesions and 19% for foveal lesions (p<0.0001). This positions pegcetacoplan as a potential first treatment for GA, a leading cause of blindness affecting over 5 million globally. Apellis plans to submit a New Drug Application to the FDA in Q2 2022.

Positive

• Pegcetacoplan reduced extrafoveal GA lesion growth by 33% (p<0.0001) in the OAKS study at month 18.
• Demonstrated a 19% reduction in foveal lesion growth (p=0.0020) in the OAKS study.
• Favorable safety profile with a combined rate of new-onset exudations at month 18 remaining low at 9.5%.

Negative

• Foveal lesion growth reduction in the DERBY study was not statistically significant (p=0.2015 and p=0.5538).
• Regulatory submission to the FDA is still pending as of Q2 2022.

• Monthly and every-other-month treatment with pegcetacoplan showed a continuous and clinically meaningful reduction in the growth of both extrafoveal and foveal lesions at month 18 (all p-values nominal)  
  • Continued to demonstrate a robust effect in patients with extrafoveal lesions 
  • Showed an improved effect in patients with foveal lesions
• Ten presentations, including three oral presentations, showcase Apellis’s leadership in retina
  

WALTHAM, Mass., May 02, 2022 (GLOBE NEWSWIRE) --  Apellis Pharmaceuticals, Inc. (Nasdaq: APLS), a global biopharmaceutical company and leader in complement, today 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, M.D., 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.
  

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“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, M.D., Ph.D., 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 U.S. Food and Drug Administration 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.

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.^4,5 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.⁶ GA is caused by destruction of retinal cells through irreversible lesion growth that is driven by excessive complement activation.⁷ 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.

Media Contact: 
Lissa Pavluk
media@apellis.com
617.977.6764

Investor Contact: 
Meredith Kaya 
meredith.kaya@apellis.com
617.599.8178 

¹Morioka et al. Incidence of endophthalmitis after intravitreal injection of an anti-VEGF agent with or without topical antibiotics. Scientific Reports 2020.
²Kiss et al. Endophthalmitis rates among patients receiving intravitreal anti-VEGF injections: a USA claims analysis. Clin Ophthalmol 2018.
³Cox et al. Inflammatory complications of intravitreal anti-VEGF injections. Journal of Clinical Medicine 2021.
⁴ 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.
⁵Wong 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.
⁶ Lindblad AS, et al, and AREDS Research Group. Arch Ophthalmol. 2009;127(9):1168-1174.
⁷ 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. 

 

FAQ

What were the results of the pegcetacoplan trials for APLS?

The pegcetacoplan trials showed significant reductions in GA lesion growth: 33% for extrafoveal and up to 19% for foveal lesions.

When does Apellis plan to submit the New Drug Application for pegcetacoplan?

Apellis plans to submit the New Drug Application for pegcetacoplan to the FDA in the second quarter of 2022.

How does pegcetacoplan impact patients with geographic atrophy?

Pegcetacoplan demonstrates a continuous reduction in GA lesion growth, potentially preserving vision for patients.

What are the safety results reported for pegcetacoplan?

At month 18, pegcetacoplan showed a favorable safety profile, with a new-onset exudation rate of 9.5%.

How many patients were involved in the DERBY and OAKS studies of pegcetacoplan?

The DERBY study enrolled 621 patients, while the OAKS study enrolled 637 patients.