Investigational Drug Reduces Biomarkers of Alzheimer Disease in Patients With Genetic Mutation

The investigational drug gantenerumab reduced biomarkers of Alzheimer disease in people with a genetic mutation that causes Alzheimer dementia at earlier ages, but it did not demonstrate evidence of a cognitive effect compared with placebo. Researchers published findings from the phase 2/3 clinical trial online ahead of print in Nature Medicine.

“The drug’s ability to shift multiple Alzheimer biomarkers toward normal indicates that it is positively affecting the disease process,” said study principal investigator Randall J. Bateman, MD, director of the Dominantly Inherited Alzheimer Network-Trials Unit at Washington University School of Medicine in St. Louis. “The effect was strong enough that we launched an open-label extension of the trial, so participants have the opportunity to stay on the drug as we continue to study it."

The study included 144 participants with dominantly inherited Alzheimer disease across asymptomatic and symptomatic disease stages: 52 people carrying the mutation were randomized to receive gantenerumab, 52 were randomized to the investigational drug solanezumab, and 40 were randomized to placebo. Treatment lasted between 4 and 7 years.

Specific Proteins in Blood Samples May Predict Increased Alzheimer’s Risk

Gantenerumab significantly reduced the amount of amyloid plaques in the brain, the study found. The drug also lowered soluble tau and phospho-tau, and slowed the rise of neurofilament light chain levels, in the cerebrospinal fluid.

However, neither gantenerumab nor solanezumab met the study’s primary endpoint: a beneficial effect on cognitive measures compared with placebo. Regardless, gantenerumab’s apparent benefit on biomarker measures of Alzheimer disease prompted researchers to offer the drug to participants in an exploratory open-label extension of the trial.

“These biomarker results suggest that gantenerumab had a favorable impact on the target and downstream markers of dominantly inherited Alzheimer disease,” said Rachelle Doody, MD, PhD, global head of neurodegeneration at Roche and Genentech, makers of gantenerumab. “We support the continued scientific investigation of gantenerumab in Washington University’s exploratory, open-label extension study.”

—Jolynn Tumolo

References

Salloway S, Farlow M, McDade E, et al. A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease [published online ahead of print, 2021 June 21]. Nat Med. doi: 10.1038/s41591-021-01369-8

Investigational Alzheimer’s drug improves biomarkers of the disease. News release. Washington University in St. Louis; June 28, 2021. Accessed June 24, 2021.