Study shows that Roche’s investigational drug for Alzheimer’s disease removes amyloid plaques from the brain¹

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced the publication of a study demonstrating that its monoclonal antibody gantenerumab removes amyloid plaques from the brain of patients with Alzheimer’s disease. The study “Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab” is published today in the October issue of Archives in Neurology.¹

It is the first time that clinical data has been published for gantenerumab, an investigational compound with a mechanism of action targeted at the early stages of Alzheimer’s disease.

Results from Phase I clinical trials and ex vivo studies demonstrated that gantenerumab treatment results in a dose-dependent reduction of brain amyloid, possibly through phagocytosis via brain microglial cells, whereas amyloid load increased in patients receiving placebo treatment.

“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 Alzheimer’s disease,” said Luca Santarelli, Global Head of Roche Neuroscience Disease Translational Area. “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.”

Gantenerumab is an investigational fully human anti-amyloid • monoclonal antibody designed to bind to amyloid plaques in the brain and remove them. It is hoped that this approach will slow progression of the disease, an outcome that cannot be achieved with currently approved treatments.

“Our objective was not only to demonstrate the effects of gantenerumab on brain amyloid, but also to start elucidating its mechanism of action,” added Santarelli, “this is extremely important to fully understand the compound’s therapeutic potential for Alzheimer’s disease.”

Since it is known that amyloid accumulates in patients’ brains about 15 years prior to the onset of dementia, ongoing and future clinical studies with gantenerumab will focus on Alzheimer’s disease in the early or prodromal phase. It is hoped that early diagnosis and intervention, before significant damage to nerve cells has occurred, will offer optimal benefit to patients.

About the study

The effect of up to six months of treatment with gantenerumab at two different doses or placebo on brain amyloid was measured in 16 patients with mild to moderate Alzheimer’s disease using positron emission tomography (PET) and the radiotracer 11C-Pittsburgh Compound B.1 In addition, Alzheimer’s disease brain slices from an independent patient sample were incubated with gantenerumab at increasing concentrations and with human microglia in an ex vivo phagocytosis assay.

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 favorable safety profile.

This is the objective of the SCarlet RoAD trial, which is set to investigate the efficacy and safety of gantenerumab in patients in the early or prodromal stage of Alzheimer’s disease. Early or prodromal Alzheimer’s disease is a condition in which a person’s memory loss is worse than can be expected by the normal ageing process alone, even though their ability to get on with daily activities is not affected to such an extent that they would be diagnosed with dementia.

The SCarlet RoAD study is currently recruiting 360 patients in 15 countries and will look at the effects that gantenerumab has on participants’ ability to remember information, to solve problems and to go about day-to-day activities. For more information: http://www.scarletroadstudy.com

About gantenerumab (RG1450)

Gantenerumab is an invetigational fully human anti-A• antibody, identified and optimized by phage display technology in cooperation with MorphoSys AG, a Munich-based Biotech. It passes the blood-brain-barrier and has a high capacity to specifically bind to cerebral amyloid plaques. While the exact mechanism of antibody-mediated reduction of the amyloid burden is controversial, there is evidence that upon binding of gantenerumab to amyloid plaques brain-resident microglial cells are activated and clear plaques by a process called phagocytosis.

More information on the putative mechanism of the anti-amyloid action of gantenerumab can be found in a recent article entitled “Gantenerumab: A novel human anti-A• antibody demonstrates sustained cerebral amyloid-• binding and elicits cell-mediated removal of human amyloid-•” published by Roche scientists in the Journal of Alzheimer’s Disease².

About Alzheimer’s disease

Alzheimer’s disease is the most common form of dementia. Alzheimer’s disease is estimated to affect 25 million people around the world with the number of diagnosed cases expected to rise dramatically in the near future3. It is expected that this illness will affect about 63 million people by 2030, and 114 million by 2050 worldwide³.

In April 2011, new international guidelines on how to diagnose Alzheimer’s were published for the first time in decades⁴. These guidelines specifically address how to diagnose Alzheimer’s in its earliest stages. They mark a major change in how experts think about and study Alzheimer’s, including the need to incorporate biomarker tests.

Roche recently sponsored a website, www.earlysymptomsalzheimers.com<http://www.earlysymptomsalzheimers.com> , designed to provide healthcare professionals, patients and caregivers with information about prodromal Alzheimer’s disease.

About Archives in Neurology

Archives of Neurology is a monthly peer-reviewed medical journal published by the American Medical Association. The mission of the Archives of Neurology is to publish scientific information primarily important for those physicians caring for people with neurologic disorders but also for those interested in the structure and function of the normal and diseased nervous system. These specific aims are (1) to make timely publication of original research of the nervous system, (2) to record observations of single patients or groups of patients that will provide new information and insights, (3) to report more basic research that is pertinent to the understanding of disease, (4) to introduce topics of practice, ethics, teaching, and history that are useful, (5) to provide a forum for discussion on topics that may be controversial in this field. This information will be published only after extensive peer review so that originality, clarity, and precision are insured.

References

1. Ostrowitzki, S. et al (2011) Mechanism of Amyloid Removal in Patients With Alzheimer Disease Treated With Gantenerumab. Archives of Neurology, 68(10)
2. Bohrmann B et al (2011) Gantenerumab: A novel human anti-Aβ antibody demonstrates sustained cerebral amyloid-β binding and elicits cell-mediated removal of human amyloid-β Journal of Alzheimer’s Disease, 26, 1-21 http://www.ncbi.nlm.nih.gov/pubmed/21955818.
3. Wimo, A. et al (2003) The magnitude of dementia occurrence in the world. Alzheimer’s Disease and Associated Disorders, 17 (2), 63-67
4. US National Institutes of Health, National Institute on Aging http://www.nia.nih.gov/NewsAndEvents/PressReleases/PR20110419guidelines.htm