Gantenerumab demonstrates mixed results in dominantly inherited Alzheimer's disease

Gantenerumab decreased molecular markers of disease, but did not demonstrate a cognitive benefit, in patients with dominantly inherited Alzheimer’s disease, according to results from a phase 2/3 trial.

DIAN-TU examined the impact of two investigational agents — gantenerumab (Roche/Genentech) and solanezumab (Eli Lilly and Company) — in people with dominantly inherited AD, a rare, early-onset form of the disease. Researchers published the results in Nature Medicine.

“[Gantenerumab’s] ability to shift multiple Alzheimer’s biomarkers toward normal indicates that it is positively affecting the disease process,” Randall J. Bateman, MD, director of DIAN-TU and the Charles F. and Joanne Knight distinguished professor of neurology at Washington University, said in a press release. “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.”

Bateman and colleagues conducted a randomized, placebo-controlled, multi-arm trial comparing gantenerumab and solanezumab in patients with different stages of dominantly inherited AD. The researchers assigned mutation carriers 3:1 to either drug or placebo.

The researchers assigned 52 patients with mutations to gantenerumab, 52 to solanezumab and to 40 placebo, evaluating the treatment over 4 to 7 years. Prevention or slowing of cognitive impairments served as the primary endpoint; secondary outcomes included improvements in clinical, cognitive, imaging and fluid biomarker.

Patients ranged from 42 to 46 years and continued follow-up, on average, for 5 years. In the gantenerumab, solanezumab and placebo groups, 40%, 58% and 55%, respectively, were women.

Neither drug provided a beneficial impact for cognitive measures, according to the study results. The patients treated with solanezumab displayed greater cognitive decline on some measures and did not show benefits on biomarkers. However, the researchers observed that gantenerumab significantly reduced amyloid plaques, cerebrospinal fluid total tau and phosphorylated tau at threonine 181 and diminished increases of neurofilament light chain. Amyloid-related imaging abnormalities with edema were observed in 19.2% of patients in the gantenerumab group, including 3 of 11 who were mildly symptomatic, and 2.5% of patients in the placebo group, but none occurred in the solanezumab group.

“Although the trial focuses on people with rare mutations, drugs that are successful in this population would be promising candidates for preventing or treating the forms of [AD] that occur more commonly in older adults,” Bateman said the press release. “The destructive molecular and cellular processes in the brain are similar in both types of the disease.”

Reference:

Washington University School of Medicine in St. Louis. Investigational Alzheimer’s drug improves biomarkers of the disease. Available at: https://medicine.wustl.edu/news/investigational-alzheimers-drug-improves-biomarkers-of-the-disease/. Accessed June 22, 2021.