Researchers were investigating a new treatment for neovascular age-related macular degeneration.
Rosenfeld: Failure of anti-PDGF trials due to study design flaws
KOLOA, Hawaii — Philip J. Rosenfeld, MD, PhD, had a caution for colleagues at Retina 2017 here: The cardinal rule of phase 3 clinical trial design is to not change what appears to work in phase 2.
Rosenfeld, whose presentation garnered him Speaker of the Day honors, talked about the recent failures of two anti-PDGF agent trials, one for pegpleranib (Fovista, Ophthotech) in combination with ranibizumab (Lucentis, Genentech), and one for rinucumab combined with aflibercept (Eylea), both Regeneron, for the treatment of neovascular age-related macular degeneration.
“There are two reasons why these studies didn’t work. Either it’s a viable treatment and the clinical trial designs were seriously flawed, or it’s a failed therapeutic strategy,” he said.
Concentrating on the failed pegpleranib trial, Rosenfeld pointed to flawed data reporting carrying over from each phase of the trials. For example, patients included in the phase 2 trial had only classic-containing lesions, whereas [subretinal hyperreflective material, SHRM]-containing lesions were included in phase 3 and was looked at in a retrospective subgroup analysis.
“In my experience, designing a prospective trial based on subgroup retrospective analyses has never worked for anything substantive,” he said.
Lesion inclusion criteria was changed from fluorescein angiography-based criteria to OCT-based criteria, and there was a lesion size imbalance at baseline in the phase 2 study that could have rendered phase 2 results misleading….