Geographic atrophy, a rare eye condition, causes central vision loss that worsens over time until the patient is completely blind.It doesn’t have an FDA-approved treatment, but Apellis Pharmaceuticals now has Additional Clinical Trial Results This provides a clearer picture of how its experimental therapy affects hallmark measures of the disease. The data solidifies a planned regulatory submission and helps support the blockbuster prospects of Apellis’ drug.
Geographic atrophy, an advanced form of age-related macular degeneration, is the degeneration of part of the retina. Waltham, Massachusetts-based Apellis estimates the disease affects 5 million people worldwide, including 1 million in the United States. Advanced retinal damage from geographic atrophy is caused by overactivity of a part of the immune system called the complement system. Apellis’ drug pegcetacoplan is a peptide designed to block complement system protein C3.
Apellis’ drugs have been validated by the FDA.In May last year, the regulatory Approved for pegcetacoplan for the treatment of paroxysmal nocturnal hemoglobinuria, a rare disorder of the complement system that affects the blood. For this indication, the drug is marketed under the name “Empaveli”. The infused drug circulates throughout the body. For geographic atrophy, Apellis has a drug injected into the eye to stop inflammation, potentially returning the retina to its normal state.
Apellis has been testing pegcetacoplan in two 36-month Phase 3 clinical trials, called OAKS and DERBY, comparing the therapy to sham surgery. Each trial had two treatment groups, one tested monthly and the other tested every other month. The primary goal of the two studies was to show that at 12 months, fewer lesions formed on the retina in patients with geographic atrophy.
Last fall, Apellis reported preliminary data Shows that OAKS achieves the trial objectives, while DERBY does not. Apellis now has 18-month data, with results from two pivotal studies showing a reduction in lesions. At 18 months, lesion growth in the OAKS study was reduced by 22% with monthly dosing and 16% with every other month dosing. In DERBY, there was a 13% reduction in lesion growth in the monthly dosing group and a 12% reduction in the every-monthly treatment group—comparable to results reported in September. But Apellis highlighted DERBY’s results from months 6 to 18, showing a 17% reduction in lesions treated monthly and a 16% reduction in treatment every other month compared to the first six months of the study.
On a March 16 conference call, CEO Cedric Francois attributed DERBY’s earlier disappointing results to an enrollment of patients whose disease had progressed rapidly. In these patients, there is a “catch-up” period, after which the effects of the drug begin to show. Francois said the analysis at 18 months was the same as the analysis at 12 months. It is important to observe trends in pegcetacoplan treatment over time, he added.
“If I have geographic atrophy today, it doesn’t matter how aggressive the disease was two years ago,” he said. “I wonder how aggressive this disease is today, because most of these patients will be treated, not for two years, but five, 10, 20 years or more. So slowing down this The progression of the disease is very important.”
With the additional positive data, Francois reiterated that Apelis plans to submit a new drug application for pegcetacoplan in the second quarter of this year. The application will include results for 18 months. These long-term data could be the key to convincing FDA reviewers. In some cases, the FDA has rejected a drug that met the primary goal of one pivotal study but was missed in another, so long-term data showing patient benefit over time helps support the drug’s case.
It is unclear whether the reduction in lesion size leads to improved vision. Chief development officer Jeffrey Eisele said vision alone would be a difficult clinical trial endpoint for geographic atrophy. He added that it is expected that treating the lesions will have an impact on vision at some point. Assessing visual acuity was one of the secondary goals of the pegcetacoplan study. Apellis plans to present the full 18-month results at a future medical meeting. Jeffrey Heier, an ophthalmologist and principal investigator of the DERBY study, said on the conference call that these long-term data are important because they show that the drug is leading to sustained improvement.
“This means that more and more retinal tissue is being preserved, and it is the loss of retinal tissue that is depriving patients of their vision,” he said.
Pegcetacoplan has been marketed for the treatment of paroxysmal nocturnal hemoglobinuria since last May. In 2021, the drug will generate $15.1 million in revenue, according to Apellis’ annual report. While sales will continue to grow, the drug will compete with Soliris and Ultomiris, two blockbuster supplemental system drugs from AstraZeneca subsidiary Alexion.
A regulatory nod to geographic shrinkage would give pegcetacoplan a first-mover advantage in this indication. But competition is coming. Iveric Bio has conducted Phase 2/3 testing with an aptamer designed to block complement system protein C5. Companies in mid-stage testing include NGM Biopharmaceuticals, which has a monoclonal antibody against C3; Annexon Biosciences, which has an antigen-binding fragment of an antibody that blocks complement system protein C1q; and Ionis Pharmaceuticals and Roche to develop an antisense oligonucleotide drug , the drug is designed to reduce the production of a protein called complement factor B.
Gene therapy represents another potential approach.Johnson & Johnson subsidiary Janssen’s CD59-targeted gene therapy in phase 2 get 2020 from Hemera Biosciences. end of last year, Novartis commits up to $1.5 billion to acquire Gyroscope Therapeuticsa biotechnology whose state-of-the-art procedure is the geographic atrophy gene therapy currently in Phase 2 testing.
Photos by Flickr users Steubert through Creative Commons license
