Higher doses of gantenerumab, a monoclonal antibody designed to bind to aggregated Aβ and remove beta plaques, will be investigated in phase III trials.
“We were able to show that gantenerumab is able to lower amyloid plaque levels in the brain, and as many as half of the people exposed to the drug for a couple of years actually showed complete clearing.”
At the 2018 Alzheimer’s Association International Conference in Chicago, Illinois, Geoff Kerchner, MD, PhD, senior medical director of neuroscience, Genentech, sat down with NeurologyLive to discuss gantenerumab, an investigational, monoclonal antibody designed to bind to aggregated Aβ and remove beta plaques.
Based on previous studies, results show that gantenerumab was able to lower amyloid plaque levels in the brain and as many as half of study participants showed complete clearing of amyloid plaques.
The Marguerite RoAD and SCarlet RoAD studies, 2 prior phase III studies that were stopped prematurely due to evidence indicating the studies would not meet their primary endpoint, were turned into open-label extensions. The updated SCarlet RoAD open-label extension safety analysis reported no new or unexpected findings with a longer exposure to high-dose gantenerumab, however, the amyloid related imaging abnormalities-edema (ARIA-E) rate increased with the dose, but the titration appeared to reduce the risk with an overall incidence <30%. Kerchner emphasizes that the data from the Marguerite RoAD and SCarlet RoAD studies supports the use of titration to a higher dose of gantenerumab in the phase III GRADUATE program.
Gantenerumab is currently being investigated in 2 phase III studies, GRADUATE 1 and 2. The studies, currently enrolling participants with early Alzheimer disease with confirmed Alzheimer disease pathology, will include higher doses of gantenerumab, about 5 times the dose that was given in the Marguerite RoAD and SCarlet RoAD studies. Subjects will be on double-blind treatment for 2 years. Target dose is achieved through a titration regimen in order to best optimize safety.