Apellis to submit 24-month phase 3 data to FDA for pegcetacoplan NDA for geographic atrophy

According to Apellis Pharmaceuticals, the submission will be a Major Amendment to the NDA, extending the review period by three months with an expected PDUFA target action date in February.

Apellis Pharmaceuticals Inc. provided an update on its New Drug Application (NDA) for intravitreal pegcetacoplan for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

According to a news release, the company plans to submit the 24-month efficacy data from the Phase 3 DERBY and OAKS studies as part of its application. The FDA was scheduled to announce an approval decision for the Apellis drug on Nov. 26. The review will now be extended by three months to February 2023.

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 FDA for the treatment of geographic atrophy.

As announced previously, these data showed robust and consistent effects with monthly and every-other-month pegcetacoplan treatment in both studies. The 24-month safety data were previously submitted as part of the 120-day update. The submission is planned for this month and will be a Major Amendment to the NDA, extending the review period by three months with an expected Prescription Drug User Fee Act (PDUFA) target action date in February, according to the company.

Cedric Francois, MD, PhD, CEO and co-founder of Apellis, pointed out in a statement that the company is looking forward to sharing with the FDA the 24-month Phase 3 data, which demonstrate robust and increasing effects over time.

“We were able to complete the full 24-month data package faster than expected, providing us with an opportunity to submit these data prior to the Nov. 26 PDUFA date, he said in the release. “These longer-term data have the potential to provide an even stronger product profile at launch.”

Francois also noted that the submission is expected to have minimal impact to the timing of the launch, which was originally planned for January. “Assuming a February PDUFA date, we would be prepared to launch immediately following an approval,” he said.

Francois also pointed out that the company will work closely with the FDA “as they complete their review of the pegcetacoplan NDA and look forward to bringing the first potential therapy to people living with GA, who currently have no approved treatment for this relentless and debilitating disease.”

Apellis remains on track to submit an EU marketing authorization application, which will also include the 24-month results, to the European Medicines Agency by the end of 2022.

Phase 3 OAKS and DERBY Studies
OAKS (n=621) and DERBY (n=637) are Phase 3, multicenter, randomized, double-masked, sham-controlled studies comparing the efficacy and safety of pegcetacoplan with sham injections across a broad and representative population of patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The primary objective of the studies was to evaluate the efficacy of monthly and every-other-month pegcetacoplan in patients with GA assessed by change in the total area of GA lesions from baseline as measured by fundus autofluorescence at 12 months. Patients continued to receive masked treatment for 24 months.

Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) and a leading cause of blindness that impacts more than five million people worldwide, including one million people in the United States.1,2

According to the news release, 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.3 GA is caused by destruction of retinal cells through irreversible lesion growth that is driven by excessive complement activation.4 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.

References

1 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.
2 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.
3 Lindblad AS, et al, and AREDS Research Group. Arch Ophthalmol. 2009;127(9):1168-1174.
4 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.