Apellis Pharmaceuticals announced that it has resumed enrollment in its two phase 3 GA trials (DERBY & OAKS) with intravitreal APL-2 for the treatment of geographic atrophy (GA).
In October 2018, Apellis communicated that the company had voluntarily implemented a pause in dosing in the phase 3 trials due to observed cases of noninfectious inflammation in patients treated from a single manufacturing lot of APL-2 intravitreal investigational material. Inflammation in all affected patients resolved.
Based on its investigation, the company believes that the likely source of inflammation resided in an impurity in the active pharmaceutical ingredient (API) that was introduced during the scale-up of the manufacturing process to produce commercial lot sizes. Apellis has modified its manufacturing process in order to eliminate the impurity and has manufactured sufficient supply of APL-2 utilizing the modified manufacturing process to conduct the entire phase 3 GA program.
Apellis continues to expect to have both trials fully enrolled by the end of the first quarter of 2020.
“Patient safety is our first priority and we feel that we can now reinitiate our phase 3 program for patients with geographic atrophy with confidence following an in-depth investigation and modifications to the manufacturing process,” Cedric Francois, CEO and co-founder of Apellis, said in a company news release. “We remain on track for full enrollment by the end of the first quarter of 2020, as originally guided. We believe that APL-2 can offer significant benefits to patients with geographic atrophy and look forward to continuing our pivotal trials for this important potential first approved treatment for GA.”
APL-2 intravitreal drug product produced from the modified manufacturing process was introduced into the company’s ongoing phase 1b trial in low vision patients with GA. Ten patients in the trial have received at least one intravitreal injection of APL-2 manufactured through the modified process and there has been no inflammation observed in any patient injected with APL-2 from this new manufacturing lot. Patients in the trial will continue to receive monthly APL-2 injections for 2 years.
The independent safety monitoring committee reviewed all non-clinical data and clinical data from the phase 1b trial and agreed that Apellis could resume dosing in the phase 3 program using APL-2 manufactured with the modified process.
“Geographic atrophy is a major cause of visual impairment across our society, profoundly and negatively impacting routine activities like driving and reading, leading to loss of independence and inability to perform every-day life activities,” Charles Wykoff, MD, PhD (Director of Research, Retina Consultants of Houston and Investigator of Apellis Phase 1b, 2 and 3 trials), said in the news release. “It is incredibly frustrating to patients and physicians that there are no approved treatments for this common, blinding disease. It is an important and exciting step forward to be reinitiating these phase 3 trials as it brings much needed hope to the GA community.”
About the DERBY and OAKS trials
The Derby and OAKS trials are 600-patient prospective, international, multicenter, randomized, double-masked, sham-injection controlled phase 3 studies assessing the efficacy and safety of multiple intravitreal (IVT) injections of APL-2 in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). For more information, please visit https://gastudy.com/.