Nov 152011

Gantenerumab, an antibody that binds to beta-amyloid, clears plaques in a matter of months, report scientists at F. Hoffmann-La Roche Ltd., Basel, Switzerland, in a study published online in Archives of Neurology.

The Phase I study of 16 Alzheimer’s patients tested gantenerumab at two doses against a placebo over six months of treatment. Senior author Luca Santarelli and colleagues used positron emission tomography (PET) scans to visualize and compare levels of amyloid plaques in the brain before and after intravenous antibody treatments, and found the decreases. The current study did not evaluate cognition. Many researchers suspect the build-up of such plaques may be a cause of this memory robbing disease.

There are, in fact, almost a dozen anti-beta-amyloid antibodies in clinical testing, including solanezumab, developed by Eli Lilly and Company, Indianapolis, Indiana, which, along with bapineuzumab, is furthest along in clinical development.

An earlier small study of the Elan Pharmaceuticals/Wyeth antibody bapineuzumab (now developed by Janssen Alzheimer Immunotherapy, Dublin, Ireland) also used PET scans to compare plaque levels in the brain before and after intravenous antibody treatment. This antibody lowered brain amyloid levels in Alzheimer’s patients by an average of 8.5 percent over 18 months, compared with a 16.9 percent increase in untreated patients.

In the current study, 18 patients, aged 50-90, who had mild to moderate Alzheimer’s disease, received either placebo or gantenerumab (60 mg or 200 mg) in up to seven monthly intravenous infusions. At the end of the study, PET scans indicated that the six patients in the low-dose group lost 15.9 percent of their plaques, while the six in the high-dose group dispatched 35.7 percent. If this holds up, it would indicate faster amyloid removal than reported for bapineuzumab.

It is unclear whether beta-amyloid clearance by gantenerumab prevents or slows cognitive decline. We await results of Phase 3 trials of solanezumab and bapineuzumab next year, which will reveal whether clearance of beta-amyloid provides any cognitive benefit in mild to moderate Alzheimer’s. Of course, studies are being planned for prodromal Alzheimer’s disease. Prodromal Alzheimer’s is a condition in which a person’s memory loss is worse than can be expected by the normal aging process, while their ability to engage in daily activities is not affected to the extent that dementia would be diagnosed. Research sites around the world are preparing to enroll patients for the SCarlet RoAD study, to evaluate efficacy and safety of gantenerumab in patients with prodromal AD.

Ostrowitzki S, Deptula D, Thurfjell L, Barkhof F, Bohrmann B, Brooks DJ, Klunk WE, Ashford E, Yoo K, Xu Z, Loetscher H, Santarelli L. Mechanism of Amyloid Removal in Patients With Alzheimer Disease Treated With Gantenerumab. Arch Neurol. 2011 Oct 10

Michael S. Rafii, M.D., Ph.D.

Director, Memory Disorders Clinic
Associate Medical Core Director, Alzheimer’s Disease Cooperative Study
University of California San Diego

This post originally appeared in Alzheimer’s Insights, an ADCS Blog.

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