Apellis Announces 24-Month Results Showing Increased Effects Over Time with Pegcetacoplan in Phase 3 DERBY and OAKS Studies in Geographic Atrophy (GA)

Rhea-AI Summary

Apellis Pharmaceuticals announced positive 24-month data from Phase 3 DERBY and OAKS studies on pegcetacoplan for geographic atrophy (GA) linked to age-related macular degeneration (AMD). Treatment effects accelerated between months 18-24, with notable reductions in GA lesion growth: DERBY showed 36% (monthly) and 29% (every-other-month), while OAKS reported 24% (monthly) and 25% (EOM) reductions. The drug maintained a favorable safety profile, with no significant adverse events. A potential first approval in the U.S. is expected by Nov. 26, 2022, with European submission planned by year-end.

Positive

• 24-month data shows increased treatment effect over time for pegcetacoplan.
• Robust reductions in GA lesion growth: 36% monthly (DERBY) and 24% monthly (OAKS).
• Favorable safety profile maintained with no reports of endophthalmitis.
• Potential to become the first approved treatment for GA in the U.S. by Nov. 26, 2022.

Negative

• No clinically meaningful difference observed in visual function endpoints at 24 months.

• Pegcetacoplan treatment effect accelerated between months 18-24, demonstrating a robust reduction of GA lesion growth compared to sham (all p-values are nominal)
  • DERBY: 36% monthly, p<0.0001; 29% every-other-month (EOM), p=0.0002
  • OAKS: 24% monthly, p=0.0080; 25% EOM, p=0.0007
    
    
• Consistent with expectations, no clinically meaningful difference on key functional endpoints observed at 24 months
  
  
• Continued to demonstrate a favorable safety profile
  
  
• Potential to become the first-ever treatment for GA with a U.S. PDUFA date of Nov. 26, 2022; EU marketing authorization application submission on track by end of year
  
  
• Conference call today at 8:30 a.m. ET
  

WALTHAM, Mass., Aug. 24, 2022 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals, Inc. (Nasdaq: APLS), a global biopharmaceutical company and leader in complement, today announced top-line data at 24 months showing increased effects over time with intravitreal pegcetacoplan, an investigational, targeted C3 therapy, in the Phase 3 DERBY and OAKS studies in geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

“I am thrilled to see the increased effects over time, which suggest that pegcetacoplan is preserving more and more photoreceptor cells that are directly responsible for vision,” said Eleonora Lad, M.D., Ph.D., lead principal investigator for the OAKS study, associate professor of ophthalmology, director of ophthalmology clinical research unit, Duke University Medical Center. “The vision loss caused by GA is devastating for patients, taking away their ability to perform critical daily tasks like driving, reading, and recognizing faces. It is very exciting to finally be on the brink of the first potential GA treatment with pegcetacoplan.”

In a pre-specified analysis of GA lesion growth over 24 months, both monthly and every-other-month (EOM) pegcetacoplan showed a clinically meaningful reduction in GA lesion growth from baseline compared to sham (all p-values are nominal):

• DERBY: 19% monthly, p=0.0004; 16% EOM, p=0.0030
• OAKS: 22% monthly, p<0.0001; 18% EOM, p=0.0002

Between months 18-24, the pegcetacoplan treatment effect accelerated compared to previous six-month periods, with robust reductions of GA lesion growth versus sham (all p-values are nominal). The increased effects were driven by a greater slowing of lesion growth by pegcetacoplan and not by an increase in the lesion growth rate in the sham group, which was highly consistent over each of the four six-month intervals (1.0+/-0.05 mm²).

• DERBY: 36% monthly, p<0.0001; 29% EOM, p=0.0002
• OAKS: 24% monthly, p=0.0080; 25% EOM, p=0.0007

Additionally, the reduction of GA lesion growth in patients with extrafoveal lesions (28% monthly; 28% EOM) was comparable to the reduction in patients with foveal lesions (34% monthly; 28% EOM) in the combined studies between months 18-24.

Consistent with expectations, no clinically meaningful difference was observed between pegcetacoplan and sham in the key secondary endpoints measuring visual function at 24 months. Studies show that GA lesion growth is correlated with loss of visual function over longer periods of time.¹ The visual function outcomes at 24 months are believed to be due to the limitations of the endpoints when used for GA and the relatively early assessment timeframe. Patients will be treated with pegcetacoplan in the GALE extension study for an additional three years.

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"These data further reinforce the breakthrough potential of pegcetacoplan, with both monthly and every-other-month treatment demonstrating increased effects across a broad patient population over 24 months,” said Jeffrey Eisele, Ph.D., chief development officer, Apellis. “With a U.S. PDUFA date in November and an EU submission planned later this year, we are committed to bringing pegcetacoplan to patients as quickly as possible.”

Pegcetacoplan continued to demonstrate a favorable safety profile, consistent with safety data to date and longer-term exposure to intravitreal injections. No cases of endophthalmitis were reported between months 18 and 24. Over 24 months, the rate of infectious endophthalmitis was 0.034% per injection and the rate of intraocular inflammation was 0.24% per injection, which continue to be generally in line with reported rates in studies of other intravitreal therapies.^2,3,4 No events of occlusive vasculitis or retinitis were observed over 24 months, and no serious adverse events of ischemic optic neuropathy were reported between months 18 and 24. The combined rate of new-onset exudations at month 24 was 11.9%, 6.7%, and 3.1% in the pegcetacoplan monthly, every-other-month, and sham groups, respectively.

The results at 24 months 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.

Detailed data will be presented at upcoming medical congresses.

Conference Call and Webcast
Apellis will host a conference call and webcast with Dr. Eleonora Lad to discuss the 24-month results of the Phase 3 DERBY and OAKS studies today, August 24 at 8:30 a.m. ET. To access the live call by phone, please pre-register for the call here. A live audio webcast of the event and accompanying slides may also be accessed through the “Events and Presentations” page of the “Investors and Media” section of the company’s website. A replay of the webcast will be available for 30 days following the event.

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 GALE
GALE is a Phase 3, multicenter, open label, extension study to evaluate the long-term safety and efficacy of intravitreal pegcetacoplan in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The objectives of the study are to evaluate the long-term incidence and severity of ocular and systemic treatment emergent adverse events as well as change in the total area of GA lesions as measured by fundus autofluorescence.

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.

Media Contact:
Lissa Pavluk
media@apellis.com
617.977.6764

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

¹Sunness JS et al. Ophthalmology. 1999;106:1768–79.
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 of the Phase 3 DERBY and OAKS studies for pegcetacoplan?

The studies demonstrated significant reductions in GA lesion growth, with pegcetacoplan achieving reductions of 36% monthly in DERBY and 24% in OAKS.

When is the PDUFA date for pegcetacoplan's approval?

The U.S. PDUFA date for pegcetacoplan is set for November 26, 2022.

What does the safety profile of pegcetacoplan indicate?

Pegcetacoplan has shown a favorable safety profile with no serious adverse events reported, including no endophthalmitis cases between months 18 and 24.

Will pegcetacoplan be available in Europe?

Yes, the company plans to submit a marketing authorization application in Europe by the end of the year.