Apellis Presents Phase 3 Functional Analyses of SYFOVRE™ (pegcetacoplan injection) for Geographic Atrophy

Rhea-AI Summary

Apellis Pharmaceuticals (APLS) announced positive results from the Phase 3 OAKS and DERBY studies for SYFOVRE™ (pegcetacoplan injection), the first approved treatment for geographic atrophy (GA) due to age-related macular degeneration (AMD). The analyses presented at the ARVO Annual Meeting demonstrated that SYFOVRE preserved visual function, showing a mean advantage of 5.6 letters in best corrected visual acuity compared to sham, and a 4.1-point improvement in quality-of-life scores. Additionally, SYFOVRE significantly slowed the loss of retinal cells necessary for vision, reducing photoreceptor cell loss by 46-53% and retinal pigmented epithelial cell loss by 20-27%. With marketing applications under review in multiple regions, a decision in the EU is anticipated in early 2024.

Positive

• SYFOVRE demonstrated preservation of 5.6 letters in visual acuity over sham treatment.
• Quality of life improved by 4.1 points, indicating clinically meaningful benefits.
• Significant reduction in the loss of photoreceptor (46-53%) and RPE cells (20-27%) compared to sham.

Negative

• None.

• Showed visual function and quality-of-life benefits in patients with extrafoveal lesions
  
  
• Slowed the loss of retinal pigmented epithelial and photoreceptor cells, both of which are required for visual function
  
  
• Eight abstracts, including three oral presentations, highlighted at ARVO annual meeting
  

WALTHAM, Mass., April 23, 2023 (GLOBE NEWSWIRE) -- Apellis Pharmaceuticals, Inc. (Nasdaq: APLS), a global biopharmaceutical company and leader in complement, today announced post hoc analyses from the 24-month, Phase 3 OAKS and DERBY studies evaluating SYFOVRE™ (pegcetacoplan injection) for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The analyses were reported during oral presentations at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting taking place April 23-27 in New Orleans.

SYFOVRE showed visual function and quality-of-life benefits in patients with extrafoveal lesions (≥0.25 mm from the foveal center). Additionally, SYFOVRE showed a meaningful reduction in the loss of photoreceptor and retinal pigmented epithelial (RPE) cells, which are both required for vision. These analyses utilized data from patients with SPECTRALIS^® optical coherence tomography (OCT) images, which allowed for artificial intelligence (AI)-based automated segmentation of the photoreceptor and RPE layers as well as determination of the amount of the central foveal region covered by the GA lesion (foveal occupancy).

SYFOVRE showed visual function and quality-of-life benefits in patients with extrafoveal lesions

In the 24-month analysis, SYFOVRE-treated patients compared to sham demonstrated:

• Preservation of 5.6 letters, equivalent to more than one line of vision on an ETDRS chart, as measured by best corrected visual acuity (BCVA).
• A 4.1-point benefit in vision-related quality-of-life outcomes, as measured by the NEI-VFQ-25. The questionnaire assesses outcomes, such as social function, driving, and dependency on others. Four points is considered clinically meaningful.¹

“Vision loss caused by GA can profoundly impact a person’s independence and well-being, so it is vital that SYFOVRE has shown slower vision loss and better quality of life compared to sham in this post hoc analysis. These data also support earlier treatment with SYFOVRE,” said Allen Chiang, M.D., presenting author and associate professor of ophthalmology at Wills Eye Hospital, Mid Atlantic Retina, and Thomas Jefferson University. “As the first and only approved medicine for GA, SYFOVRE represents a new treatment era for this devastating disease.”

Due to sample size considerations, every-other-month and monthly data from OAKS and DERBY were combined for the SYFOVRE (n=131) and sham (n=61) groups. These data are in addition to the functional benefit outcomes previously reported in the post hoc junctional zone microperimetry analysis.

SYFOVRE slowed photoreceptor and RPE cell loss compared to sham

In the 24-month analysis of OAKS (n=456) and DERBY (n=435), SYFOVRE demonstrated a meaningful reduction in the loss of both photoreceptor and RPE cells compared to sham (all p-values nominal):

• Photoreceptor cells
  • Every-other-month: 46% (OAKS; p<0.0001) and 46% (DERBY; p<0.0001)
  • Monthly: 53% (OAKS; p<0.0001) and 47% (DERBY; p<0.0001)
• RPE cells
  • Every-other-month: 20% (OAKS; p=0.0002) and 21% (DERBY; p=0.0005)
  • Monthly: 22% (OAKS; p=0.0002) and 27% (DERBY; p<0.0001)

RPE cells maintain the integrity of photoreceptor cells, and both types of cells are required for vision. Data were consistent when comparing SYFOVRE-treated study eyes to the untreated fellow eyes.

“We are proud to share these data as part of our eight presentations at this year’s ARVO meeting, which showcase our leadership in GA and retina,” said Caroline Baumal, M.D., chief medical officer at Apellis. “SYFOVRE is a gamechanger for GA as the first and only treatment for this relentless disease, and we look forward to exploring its potential to treat other complement-driven retina diseases with significant unmet needs.”

Marketing applications are currently under review with five regulatory agencies worldwide. A decision in the EU is expected in early 2024, and decisions in Canada, Australia, Switzerland, and the United Kingdom are expected in the first half of 2024.

Presentations will be available on the “Events and Presentations” page of the “Investors and Media” section of the company’s website.

About the Visual Function Methodology
The visual function analysis accounts for key predictors of vision loss including distance to the fovea (≥0.25 mm from the foveal center) and foveal occupancy. The analysis was adjusted for baseline imbalances in disease characteristics, including foveal occupancy.

About the Phase 3 OAKS and DERBY Studies
OAKS (n=637) and DERBY (n=621) are Phase 3, multicenter, randomized, double-masked, sham-controlled studies comparing the efficacy and safety of SYFOVRE™ (pegcetacoplan injection) with sham injections across a broad and heterogenous population of patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The studies evaluated the efficacy of monthly and every-other-month SYFOVRE in patients with GA assessed by change in the total area of GA lesions from baseline as measured by fundus autofluorescence.

In Phase 3 studies at 24 months, both every-other-month and monthly SYFOVRE reduced GA lesion growth with increasing effects over time and showed a well-demonstrated safety profile.

About Geographic Atrophy (GA)
Geographic atrophy (GA) is an advanced form of age-related macular degeneration and a leading cause of blindness worldwide, impacting more than one million Americans and five million people worldwide.^2,3 It is a progressive and irreversible disease caused by the growth of lesions, which destroy the retinal cells responsible for vision. The vision loss caused by GA severely impairs independence and quality of life by making it difficult to participate in daily activities. On average, it takes only 2.5 years for GA lesions to start impacting the fovea, which is responsible for central vision.⁴

About SYFOVRE™ (pegcetacoplan injection)
SYFOVRE™ (pegcetacoplan injection) is the first and only approved therapy for geographic atrophy (GA). By targeting C3, SYFOVRE is designed to provide comprehensive control of the complement cascade, part of the body’s immune system. SYFOVRE is approved in the United States for the treatment of GA secondary to age-related macular degeneration.

U.S. Important Safety Information for SYFOVRE™ (pegcetacoplan injection)
CONTRAINDICATIONS

• SYFOVRE is contraindicated in patients with ocular or periocular infections, and in patients with active intraocular inflammation
  

WARNINGS AND PRECAUTIONS

• Endophthalmitis and Retinal Detachments
  • Intravitreal injections, including those with SYFOVRE, may be associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering SYFOVRE to minimize the risk of endophthalmitis. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately.
• Neovascular AMD
  • In clinical trials, use of SYFOVRE was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (12% when administered monthly, 7% when administered every other month and 3% in the control group) by Month 24. Patients receiving SYFOVRE should be monitored for signs of neovascular AMD. In case anti-Vascular Endothelial Growth Factor (anti-VEGF) is required, it should be given separately from SYFOVRE administration.
• Intraocular Inflammation
  • In clinical trials, use of SYFOVRE was associated with episodes of intraocular inflammation including: vitritis, vitreal cells, iridocyclitis, uveitis, anterior chamber cells, iritis, and anterior chamber flare. After inflammation resolves, patients may resume treatment with SYFOVRE.
• Increased Intraocular Pressure
  • Acute increase in IOP may occur within minutes of any intravitreal injection, including with SYFOVRE. Perfusion of the optic nerve head should be monitored following the injection and managed as needed.

ADVERSE REACTIONS

• Most common adverse reactions (incidence ≥5%) are ocular discomfort, neovascular age-related macular degeneration, vitreous floaters, conjunctival hemorrhage.
  

Please see accompanying full Prescribing Information for more information.

About Apellis 
Apellis Pharmaceuticals, Inc. is a global biopharmaceutical company that combines courageous science and compassion to develop life-changing therapies for some of the most challenging diseases patients face. We ushered in the first new class of complement medicine in 15 years and now have two approved medicines targeting C3. These include the first and only therapy for geographic atrophy, a leading cause of blindness around the world. With nearly a dozen clinical and pre-clinical programs underway, we believe we have only begun to unlock the potential of targeting C3 across many serious 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 the commercial availability of SYFOVRE. 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 SYFOVRE will be commercially available when expected; whether clinical trials of SYFOVRE indicate an apparent positive effect that is greater than the actual positive effect, whether SYFOVRE will receive approval from 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 21, 2023 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

¹Suner et al. Responsiveness of NEI VFQ-25 to changes in visual acuity in neovascular AMD: Validation studies from two phase 3 clinical trials. Invest Ophthalmol Vis Sci 2009;50(8):3629-35.
²Rudnicka 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.
³ 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.
⁴ Lindblad AS, et al, and AREDS Research Group. Arch Ophthalmol. 2009;127(9):1168-1174.

FAQ

What were the results of the Phase 3 OAKS and DERBY studies for APLS?

The studies showed that SYFOVRE improved visual acuity by 5.6 letters and quality of life by 4.1 points compared to sham.

What is SYFOVRE and its significance for APLS?

SYFOVRE is the first approved treatment for geographic atrophy due to AMD, potentially changing the treatment landscape.

When are the regulatory decisions for SYFOVRE expected?

Decisions in the EU are expected in early 2024, with additional reviews in Canada, Australia, Switzerland, and the UK anticipated in the first half of 2024.

How did SYFOVRE impact retinal cell loss in the studies?

SYFOVRE significantly slowed the loss of photoreceptor and retinal pigmented epithelial cells, crucial for vision, compared to sham treatments.