Apellis says it will be able to restart two trials of its APL-2 drug for eye disease geographic atrophy (GA) next year, after finding the cause of side effects that brought the program to a halt.
Enrollment was halted in the DERBY and OAKS trials in October after noninfectious inflammation was seen in GA patients receiving the drug by injection into the eye. After an investigation, Apellis thinks that they were caused by an “impurity or contaminant” in the active pharmaceutical ingredient (API) that affected a single manufacturing lot of the product.
It has also ruled out a formulation change for APL-2 that took place between the phase 2 FILLY trial and the phase 3 studies, as well as the fill-and-finish process for the drug. It implemented some improvements to its manufacturing process and has enough new API in hand to complete the phase 3 trials. The API has passed initial nonclinical tests to ensure it doesn’t cause inflammation but may also be put through a phase 1b trial as a final safety check before DERBY and OAKS resume.
It’s a relief for Kentucky-based Apellis, which saw its shares slump in the wake of the halt—which came a few months after its $150 million IPO—on fears that the reactions could have been caused by the pharmacology or chemical composition of APL-2. Now, the company says it will resume enrollment in the second quarter of 2019 and should have both trials fully recruited in the first quarter of 2020—within its original timeline for the program.
A subcutaneous formulation of the complement C3 inhibitor is also in trials for paroxysmal nocturnal hemoglobinuria and is vying to take on Alexion’s Soliris (eculizumab)—a C5 inhibitor which is currently the only FDA-approved drug for this rare and serious anemic blood disorder—but GA is thought to be the biggest market opportunity.
It’s an advanced form of age-related macular degeneration estimated to affect around a million people in the U.S. alone. There are no approved drugs for GA, a progressive condition that leads to central blind spots and permanent loss of vision.
After the halt was announced, analysts at GlobalData suggested that it could give an opportunity to rival GA drug developer Ophthotech, which is due to report phase 2b results with its Zimura (avacincaptad pegol) complement inhibitor next year. There’s a lot at stake; the analysts think that the GA market in seven major pharma markets—the U.S., France, Germany, Italy, Spain, U.K., and Japan—could go from a standing start to reach $3 billion by 2026.
“We are pleased to have clarity around our path forward so that we can continue development of this important potential treatment, and on schedule,” said Apellis’ co-founder and CEO Cedric Francois, M.D., Ph.D., in a release. “We believe that APL-2 has the potential to offer significant benefit to patients with geographic atrophy, a disease that results in blindness, and for which there are no FDA-approved treatments.”