BioPharma, Pharma

Apellis Pharma eyes a shot at getting first FDA approval in rare vision disorder

Apellis Pharmaceuticals has additional clinical data that show its drug having an effect on geographic atrophy, a rare vision-loss disorder with no FDA-approved treatment. The biotech plans to include the latest results in a new drug application being readied for submission in coming months.


The rare eye disease geographic atrophy causes the loss of central vision, which worsens with the passing of years until a patient becomes completely blind. It has no FDA-approved treatment, but Apellis Pharmaceuticals now has additional clinical trial results that give more clarity about how its experimental therapy affects a hallmark measure of the disease. The data solidify the planned regulatory submission and help support the Apellis drug’s blockbuster prospects.

Geographic atrophy is an advanced form of age-related macular degeneration, a deterioration of a part of the retina. Waltham, Massachusetts-based Apellis estimates the disease affects 5 million worldwide, including 1 million in the U.S. The advanced retinal damage from geographic atrophy is caused by excessive activity of a part of the immune system called the complement system. Apellis’s drug, pegcetacoplan, is a peptide designed to block the complement system protein C3.

Apellis already has FDA validation for its drug. Last May, the regulator approved pegcetacoplan as a treatment for paroxysmal nocturnal hemoglobinuria, a rare complement system disorder affecting the blood. For that indication, the drug is marketed under the name “Empaveli.” That infused drug circulates systemically. For geographic atrophy, Apellis has a version of the drug that is injected into the eye where it’s intended to stop inflammation, potentially restoring the retina to a normal state.

Apellis has been testing pegcetacoplan in two 36-month Phase 3 clinical trials, named OAKS and DERBY, comparing the therapy to a sham procedure. Each trial has two treatment arms, one testing every month dosing and the other group testing every-other-month dosing. The main goal of both studies is showing, at 12 months, a reduction in the lesions that form on retinas of geographic atrophy patients.

Last fall, Apellis reported preliminary data showing that OAKS met the trial goal while DERBY did not. Apellis now has data at 18 months, and the results from both pivotal studies show reductions in the lesions. At 18 months, lesion growth in the OAKS study was reduced by 22% with monthly dosing and by 16% with every-other-month dosing. In DERBY, lesion growth was reduced by 13% in the monthly dosing group and by 12% with every-other-month treatment—comparable to the results reported in September. But Apellis highlights DERBY’s results from months six to 12, where lesions were reduced by 17% with monthly treatment and by 16% with every-other-month treatment compared to the first six months of the study.

Speaking on a March 16 conference call, CEO Cedric Francois attributed the earlier disappointing results in DERBY to the enrollment of patients with fast-progressing disease. In these patients, there’s a “catch-up” period, after which the drug’s effects start to show. Francois said the analysis done at 18 months is the same as the analysis that was done at 12 months. He added that it’s important to look at the trends of pegcetacoplan treatment over time.

“If I have geographic atrophy today, it doesn’t really matter how aggressive the disease was two years ago,” he said. “I want to know how aggressive the disease is today, because most of these patients are going to be on treatments for not two, but five, 10 years, 20 years or longer. So, slowing down the progression of that disease is something very important.”

With the additional positive data, Francois reaffirmed that Apellis plans to submit a new drug application for pegcetacoplan in the second quarter of this year. That application will include the 18-month results. These longer-term data could be key to persuading FDA reviewers. There are instances in which the FDA has turned down drugs that met the main goal of one pivotal study but missed in the other, so longer-term data showing patient benefit over time help support the case for pegcetacoplan.

What is not yet clear is whether the reduction in lesion size is leading to vision improvement. Chief Development Officer Jeffrey Eisele said that vision alone would be a difficult clinical trial endpoint for geographic atrophy. He added that the expectation is that treating the lesions would have impact on vision at some point. Assessing vision is one of the secondary goals of the pegcetacoplan studies. Apellis plans to present full 18-month results at a future medical meeting. Jeffrey Heier, an ophthalmologist and the principal investigator of the DERBY study, said on the call that these longer-term data are important because they show that the drug is leading to continued improvement.

“This means that there is an increasing amount of retinal tissue being preserved, and it is the loss of retinal tissue that is robbing patients of their vision,” he said.

Pegcetacoplan has been commercially available for paroxysmal nocturnal hemoglobinuria since last May. In 2021, the drug accounted for $15.1 million in revenue, according to Apellis’s annual report. While sales will continue to grow, the drug competes against Soliris and Ultomiris, two blockbuster complement system drugs from AstraZeneca subsidiary Alexion.

A regulatory nod in geographic atrophy would give pegcetacoplan first-mover advantage in that indication. But competition is coming. Iveric Bio has reached Phase 2/3 testing with an aptamer designed to block the complement system protein C5. Companies that are in mid-stage testing include NGM Biopharmaceuticals with a monoclonal antibody that targets C3; Annexon Biosciences with an antibody antigen-binding fragment that blocks the complement system protein C1q; and Ionis Pharmaceuticals and Roche, partners on an antisense oligonucleotide drug designed to reduce production of a protein called complement factor B.

Gene therapy represents yet another potential approach. Johnson & Johnson subsidiary Janssen is in Phase 2 with a CD59-targeting gene therapy acquired in 2020 from Hemera Biosciences. And late last year, Novartis committed up to $1.5 billion to acquire Gyroscope Therapeutics, a biotech whose most advanced program is a geographic atrophy gene therapy currently in Phase 2 testing.

Photo by Flickr user stubot via a Creative Commons license