Apellis Announces Pegcetacoplan Showed Continuous and Clinically Meaningful Effects at Month 18 in Phase 3 DERBY and OAKS Studies for Geographic Atrophy (GA)

Rhea-AI Summary

Apellis Pharmaceuticals (APLS) released positive data from the Phase 3 DERBY and OAKS studies, showcasing that intravitreal pegcetacoplan effectively reduces geographic atrophy (GA) lesion growth after 18 months. Both monthly and every-other-month treatments demonstrated significant efficacy with p-values below 0.05. The favorable safety profile was maintained, with low rates of infections. These results will support a New Drug Application (NDA) submission to the FDA planned for Q2 2022, with a conference call scheduled for today to discuss findings.

Positive

• Pegcetacoplan reduced GA lesion growth by 22% (monthly) and 16% (every-other-month) in OAKS, and 13% (monthly) and 12% (every-other-month) in DERBY at 18 months.
• Treatment effects improved over time with reductions in GA lesion growth increasing from 13% to 21% for monthly treatment from months 0-6 to 12-18.
• Pegcetacoplan demonstrated a favorable safety profile with infection rates consistent with other therapies.

Negative

• None.

• Both monthly and every-other-month pegcetacoplan continued to reduce GA lesion growth compared to pooled sham at 18 months with all p-values (nominal) below 0.05
  
  • Treatment effects in DERBY were comparable to OAKS during months 6-18
  • Pegcetacoplan continued to demonstrate a favorable safety profile 
    
• Combined 18-month data show the potential for improving treatment effects over time
• Data to be included in the NDA submission planned for Q2
• Conference call today at 8:30 a.m. ET

WALTHAM, Mass., March 16, 2022 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals, Inc. (Nasdaq: APLS), a global biopharmaceutical company and leader in complement, today announced longer-term data from the Phase 3 DERBY and OAKS studies, which showed that intravitreal pegcetacoplan, an investigational, targeted C3 therapy, continued to reduce geographic atrophy (GA) lesion growth and demonstrate a favorable safety profile at month 18 for the treatment of GA secondary to age-related macular degeneration (AMD). These data will be included in the New Drug Application (NDA) that the company plans to submit to the U.S. Food and Drug Administration (FDA) in the second quarter of 2022.

“It is exciting to see these positive data with pegcetacoplan, which showed continuous and potentially improving effects over time. These 18-month results provide further evidence that pegcetacoplan meaningfully slows disease progression and has the potential to preserve vision longer,” said Jeffrey S. Heier, M.D., principal investigator of the DERBY study and director, retina service and director, retinal research, Ophthalmic Consultants of Boston. “In my practice, I have seen how devastating it can be for people living with GA to lose more of their vision year after year. There is an urgent unmet need in GA, and these results reinforce the potential of pegcetacoplan to become the first-ever treatment for patients with this debilitating disease.”

Monthly and Every-Other-Month Pegcetacoplan Showed Continuous Effects Over Time

A Media Snippet accompanying this announcement is available by clicking on the image or link below:

In a longer-term analysis of the primary endpoint, pegcetacoplan continued to reduce GA lesion growth compared to pooled sham at month 18 (all p-values are nominal):

• In OAKS, pegcetacoplan reduced GA lesion growth with both monthly (22%; p<0.0001) and every-other-month treatment (16%; p=0.0018).
• In DERBY, pegcetacoplan reduced GA lesion growth with both monthly (13%; p=0.0254) and every-other-month treatment (12%; p=0.0332).
• Pegcetacoplan demonstrated marked improvements in DERBY during months 6-12 with reductions of 17% with monthly and 16% with every-other-month treatment compared to months 0-6, and the treatment effects were sustained through month 18. The treatment effects observed in DERBY were comparable with OAKS during months 6-18.
• Data at 18 months from the combined studies show the potential for improving treatment effects with pegcetacoplan over time. The reduction in GA lesion growth improved with monthly pegcetacoplan treatment from 13% to 21% from months 0-6 to months 12-18. The reduction in GA lesion growth improved with every-other-month pegcetacoplan treatment from 12% to 17% from months 0-6 to months 12-18.

“Pegcetacoplan is the only therapy to continuously reduce GA lesion growth across a large and broad patient population in Phase 3 studies. Building on our 12-month results, both monthly and every-other-month pegcetacoplan demonstrated clinically meaningful effects and a favorable safety profile with longer-term use,” said Federico Grossi, M.D., Ph.D., chief medical officer at Apellis. “We look forward to submitting these data to the FDA and working with regulatory agencies to bring pegcetacoplan to people living with GA around the world as quickly as possible.”

At month 18, pegcetacoplan continued to demonstrate a favorable safety profile, consistent with safety at 12 months and longer-term exposure to intravitreal injections. The rate of infectious endophthalmitis was 0.044% per injection, and the rate of intraocular inflammation was 0.23% per injection. Rates of endophthalmitis and intraocular inflammation continue to be generally in line with those reported in studies of other intravitreal therapies.^1,2,3 No events of retinal vasculitis or retinal vein occlusion were observed. The combined rate of new-onset exudations at month 18 was 9.3%, 6.2%, and 2.9% in the pegcetacoplan monthly, every-other-month, and sham groups, respectively.

Detailed data will be presented at upcoming scientific meetings.

Conference Call and Webcast
Apellis will host a conference call and webcast with Dr. Jeffrey Heier to discuss the 18-month results of the Phase 3 DERBY and OAKS studies today, March 16 at 8:30 a.m. ET. To access the live call by phone, please pre-register for the call here. The conference ID is 9238459. 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 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 are the key results of the pegcetacoplan trials at 18 months?

Pegcetacoplan showed significant reductions in GA lesion growth, with 22% reduction in OAKS and 13% reduction in DERBY, both with a favorable safety profile.

When will Apellis submit the NDA for pegcetacoplan?

The NDA submission for pegcetacoplan is planned for Q2 2022.

What does the favorable safety profile of pegcetacoplan mean?

The favorable safety profile indicates low rates of infections and inflammation, aligning with other intravitreal therapies, which is crucial for patient safety.

What is the significance of pegcetacoplan's trial results?

The trial results signify a potential breakthrough in treating geographic atrophy, addressing an urgent unmet medical need.

What are the next steps for pegcetacoplan after the trial results?

Following the trial results, Apellis plans to submit the NDA to the FDA and continue working with regulatory agencies for approval.