Gantenerumab

TUESDAY, March 25, 2025 -- For individuals with dominantly inherited Alzheimer disease (DIAD), long-term treatment with gantenerumab, an anti-amyloid beta antibody, may delay clinical decline, according to a study published in the April issue of The Lancet Neurology . Randall J. Bateman, M.D., from Washington University School of Medicine in St. Louis, and colleagues conducted a three-year open-label extension (OLE) study to examine the safety and efficacy of long-term treatment with high-dose gantenerumab. The study was conducted at 18 sites and enrolled 73 individuals at risk for DIAD, who had participated in a phase 2/3 multiarm trial (DIAN-TU-001) and had known mutation status. The study was stopped early after a prespecified interim analysis due to lack of a regulatory path for gantenerumab. The primary outcome for the final analysis was the amyloid plaque measure ¹¹C-Pittsburgh compound-B positron emission tomography (PiB-PET) standardized uptake value ratio (SUVR [PiB-PET SUVR]) assessed in the modified intention-to-treat group at three years. The researchers found that 47 participants stopped dosing due to early study termination and 13 discontinued prematurely for other reasons. At the interim analysis, in asymptomatic mutation carriers, the hazard ratio for clinical decline in the Clinical Dementia Rating-Sum of Boxes was 0.79 for participants treated with gantenerumab in either the double-blind or OLE period (95 percent confidence interval, 0.47 to 1.32) and 0.53 for those treated with gantenerumab the longest (95 percent confidence interval, 0.27 to 1.03). The adjusted mean change from OLE baseline to year 3 in PiB-PET SUVR was −0.71 SUVR at the final analysis. "I am highly optimistic now, as this could be the first clinical evidence of what will become preventions for people at risk for Alzheimer's disease ," Bateman said in a statement. Several authors disclosed ties to biopharmaceutical companies, including F. Hoffmann-La Roche/Genentech, which is developing gantenerumab.

MONDAY, March 24, 2025 -- The best evidence yet that cutting-edge Alzheimer’s disease drugs might indeed ward off the degenerative brain disease has emerged from a small-scale study. An experimental drug that clears amyloid beta from the brain cut the risk of developing Alzheimer’s by 50% among a group of 22 people with genetic mutations that all but guarantee they would eventually develop the brain disease, researchers reported March 19 in The Lancet Neurology . The drug, gantenerumab, was abandoned by its developers, but subsequent anti-amyloid drugs lecanemab ( Leqembi ) and donanemab ( Kisunla ) have since received federal government approval and are being used to treat early Alzheimer’s. “Everyone in this study was destined to develop Alzheimer’s disease and some of them haven’t yet,” senior author Dr. Randall Bateman , a professor of neurology at Washington University School of Medicine in St. Louis, said of the gantenerumab study. “We don’t yet know how long they will remain symptom-free – maybe a few years or maybe decades,” Bateman continued. “In order to give them the best opportunity to stay cognitively normal, we have continued treatment with another anti-amyloid antibody in hopes they will never develop symptoms at all.” “What we do know is that it’s possible at least to delay the onset of the symptoms of Alzheimer’s disease and give people more years of healthy life,” he concluded. All these drugs were developed based on what’s called the “amyloid hypothesis” of Alzheimer’s, which holds that the disease is caused at least in part by sticky, toxic proteins called amyloid beta that build up in the brain. For this study, Bateman and his colleagues tested the anti-amyloid drug gantenerumab among 73 people who carry genetic mutations that make them destined to fall prey to Alzheimer’s in middle-age. The 22 patients highlighted in the new paper had no cognitive problems at the start of the study, and received gantenerumab the longest, researchers said. When the trial concluded in 2020, researchers reported that gantenerumab had indeed lowered amyloid levels in the patient’s brains, but the drug’s effectiveness in warding off Alzheimer’s was inconclusive. Despite ongoing research, gantenerumab makers Roche and Genentech discontinued the drug’s development in November 2022, given that clinical trials had failed to prove any benefit in staving off cognitive decline. But researchers kept following the initially healthy patients treated with gantenerumab, who by this time had received the drug for eight years on average. Eventually, they found a strong effect in this longest-treated group, with the drug cutting the risk of developing Alzheimer’s symptoms in half. “I am highly optimistic now, as this could be the first clinical evidence of what will become preventions for people at risk for Alzheimer’s disease,” Bateman said. “One day soon, we may be delaying the onset of Alzheimer’s disease for millions.” Anti-amyloid drugs are expensive and not without risk. They can cause brain swelling, and in this small gantenerumab group rates of this side effect were one-third higher than in the original clinical trial, 30% versus 19%. But these results show that anti-amyloid drugs might one day be proven effective as preventive medications for Alzheimer’s disease, rather than treatments given once someone has the disorder, researchers said. “These exciting preliminary findings hint very clearly at the potential role of lowering beta amyloid in prevention of Alzheimer’s disease,” Maria Carrillo , chief science officer for the Alzheimer’s Association, concluded in a news release. Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.