Roche's Gantenerumab Demonstrates Biomarker Reduction in Dominantly Inherited Alzheimer’s Disease Patients

Compiled & Translated by | Fan Dongdong

In a Phase 2/3 trial led by Washington University School of Medicine and reported last year, experimental anti-amyloid antibodies from Eli Lilly and Roche failed to improve symptoms of Alzheimer’s disease, raising serious doubts about the future prospects of these drugs. Recently, the principal investigator stated that a new analysis of the trial results indicates that one of the drugs, Roche’s gantenerumab, may benefit a subset of patients.

A study published by the University of Washington in *Nature Medicine* indicates that among trial participants with Dominantly Inherited Alzheimer’s Disease (DIAD), treatment with a Roche drug can reduce brain biomarkers of disease and neurodegeneration associated with early-onset memory loss and other symptoms. The study did not demonstrate evidence of cognitive benefit for Alzheimer’s patients, although the trial was not designed to assess the cognitive impact of gantenerumab in patients who began treatment prior to symptom onset. The University of Washington has now launched an extension study in which patients receiving gantenerumab will continue treatment and have their symptoms continuously monitored over time.

Following the initial release of the topline results from the Phase 2/3 trials of solanezumab and gantenerumab, Roche explicitly stated that it has no intention of discontinuing the development of anti-amyloid antibodies. In contrast, Eli Lilly had already suspended the development of solanezumab in 2016. Patients in the initial trial were randomly assigned to receive either Lilly’s solanezumab, Roche’s gantenerumab, or a placebo, and were followed up for up to seven years.

Researchers reported that 52 patients treated with gantenerumab exhibited a reduction in amyloid plaques in the brain (a hallmark of Alzheimer’s disease) and decreased levels of the tau protein. The researchers also identified a key biomarker of neurodegeneration in the patients: elevated levels of neurofilament light chain in the cerebrospinal fluid, from which they concluded that gantenerumab appeared to slow the increase of this biomarker.

The amyloid hypothesis for Alzheimer’s disease is experiencing a resurgence, thanks to Biogen’s Aduhelm. Despite widespread skepticism regarding its efficacy and strong public outcry over its price tag of up to $56,000, this anti-amyloid drug was recently approved by the FDA.

Nevertheless, some clinicians still attempt to use anti-amyloid therapy for Alzheimer’s disease before patients develop major cognitive symptoms. Jefferies analysts stated last week that a survey of physicians revealed that 35% expressed strong interest in prescribing Aduhelm for Alzheimer’s patients with mild symptoms. The Washington University study on Roche’s gantenerumab is supported by the company and several funders, including the Alzheimer’s Association and the U.S. National Institutes of Health. The study enrolled patients with rare genetic mutations that cause early-onset Alzheimer’s disease, who have already begun to exhibit symptoms such as memory decline.

In a statement, Rachelle Doody, MD, Head of Neurodegenerative Diseases at Roche and Genentech, stated that biomarker data from the study indicate that "gantenerumab had a favorable impact on the target and downstream markers of dominantly inherited Alzheimer’s disease." Randall J. Bateman, MD, Professor of Neurology at Washington University and principal investigator of the trial, added that "the destructive molecular and cellular processes in the brain are similar across both types of the disease." Although the study focused on individuals with a genetic predisposition to early-onset Alzheimer’s disease, results from the extension arm may be relevant to the treatment of patients with the more common form of the disease.

Source: Roche's Alzheimer's antibody lowers biomarkers in inherited form of disease, though impact on symptoms is unclear