Roche has announced the publication of promising Phase I data demonstrating that its monoclonal antibody gantenerumab removes amyloid plaques from the brain of patients with Alzheimer's disease.
The Swiss major says that the results from a small 16-patient study, published in the Archives of Neurology, represent the first time that clinical data has been published for gantenerumab, which has a mechanism of action targeted at the early stages of AD. The compound is designed to bind to amyloid plaques in the brain and remove them and it is hoped that this approach will slow progression of the disease, "an outcome that cannot be achieved with currently-approved treatments".
The study tested gantenerumab at two doses against placebo over six months and treatment with the Roche drug led to a dose-dependent reduction of brain amyloid, while amyloid load increased in patients on placebo. "These results and especially the rapidity of the effects observed on amyloid removal are very encouraging and pave the way for the development of a novel treatment for AD," said Luca Santarelli, head of Roche's global neuroscience disease unit.
He added that "our approach is to utilise biomarkers to diagnose and treat the disease at a very early stage before significant damage to the brain has occurred". It is known that amyloid accumulates in patients' brains about 15 years prior to the onset of dementia, so early diagnosis and intervention, before significant damage to nerve cells has occurred, would be a major advance.
360-patient study recruiting
The company says that the next step will be to investigate "whether removal of brain amyloid translates into clinical benefit for patients at doses of gantenerumab that reduce brain amyloid and are well tolerated, with a favourable safety profile". As such, it is recruiting 360 patients in 15 countries for a trial looking at gantenerumab in patients in the early or prodromal stage of AD.
Gantenerumab was "identified and optimised by phage display technology" in cooperation with Germany's MorphoSys, Roche noted. It passes the blood-brain-barrier and has a high capacity to specifically bind to cerebral amyloid plaques and "while the exact mechanism of antibody-mediated reduction of the amyloid burden is controversial", there is evidence that "brain-resident microglial cells are activated and clear plaques by a process called phagocytosis".
AD is estimated to affect 25 million people around the world, Roche says, "with the number of diagnosed cases expected to rise dramatically in the near future". The figure could reach 63 million people by 2030, and 114 million by 2050.