Donanemab-AZBT

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.

The Knight Family DIAN-TU platform trial was initiated in 2012. Image credit: Shutterstock / Orawan Pattarawimonchai. Roche’s discontinued Alzheimer’s disease drug has shown signs that it could prevent onset of the disease. The Phase II/III Knight Family Dominantly Inherited Alzheimer Network-Trials Unit (DIAN-TU) platform trial (NCT05552157), was conducted by researchers at the Washington University School of Medicine. The study evaluated Roche’s gantenerumab in 73 participants aged between 30 to 50 with rare, inherited genetic mutations that cause the overproduction of amyloid in the brain, which investigators say all but guarantees they will develop Alzheimer’s disease in middle age. The participants were dosed in the DIAN-TU-001 (NCT01760005) and the open-label extension (OLE) (NCT06424236) studies. Data from the DIAN-TU-001 trial showed that Roche’s gantenerumab, an amyloid beta peptide inhibitor, reduced amyloid levels in the brain and improved some measures of Alzheimer’s proteins, but did not meet the primary endpoint. Now, new OLE study data published in The Lancet has shown the anti-amyloid drug cut the risk of developing symptoms by 50%. For a subgroup of 22 participants who had no cognitive problems at the study’s start and who received the drug the longest – an average of eight years – the treatment cut the risk of developing symptoms, according to a primary analysis of the data and supported by multiple sensitivity analyses supporting the trend. The investigator’s calculation not only considers how many people developed symptoms but also when symptoms emerged for each participant compared to his or her expected age of onset. That means the effect size could change as time goes on. Investigators said that some participants in the study are at or just past their expected age of onset and if they continue to go without developing symptoms, the effect size will increase. However, if some who are healthy now develop symptoms in later years, this would reduce the effect size. The Charles F and Joanne Knight Distinguished Professor of Neurology at Washington University School of Medicine, Dr Randall Bateman, said: “We don’t yet know how long they will remain symptom-free – maybe a few years or maybe decades.” The DIAN-TU-001 study was launched in 2012, and all participants in the trial had no to very mild cognitive decline and were within the range of 15 years before to ten years after their expected age of Alzheimer’s onset, based on family history. When the trial concluded in 2020, it was not clear whether Roche’s therapy would provide cognitive benefit to those without symptoms. This caused investigators to launch the OLE study to evaluate gantenerumab’s effects and determine whether higher doses or longer treatment could prevent or delay cognitive decline. Investigators hope that this result could also translate to those at risk of late-onset Alzheimer’s disease. “If late-onset Alzheimer’s prevention trials have similar results to the DIAN-TU trials, there soon could be Alzheimer’s preventions available for the general population,” Bateman added. “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.  One day soon, we may be delaying the onset of Alzheimer’s disease for millions.” Patients switched to Leqembi The therapy was discontinued after Roche’s Phase III programme as the GRADUATE I and II studies failed to meet their endpoints . As a result, participants receiving gantenerumab in DIAN-TU OLE were switched to Eisai and Biogen’s anti-amyloid therapy Leqembi (lecanemab). Another study, the DIAN-TU-002 trial (NCT06647498), has been launched as part of the platform series, evaluating Eli Lilly’s remternetug in young adults to assess its efficacy as a preventative of the disease. Eli Lilly is already a big name in the Alzheimer’s disease space after the launch of the anti-amyloid therapy Kinsula (donanemab). An issue with anti-amyloid drugs such as Leqembi, Kinsula and gantenerumab is the adverse event (AE) amyloid-related imaging abnormalities (ARIA). In the OLE study of gantenerumab, ARIA rates were one-third higher than in the original clinical trial (30% versus 19%), which the researchers attribute to the higher doses used in the extension. Two participants developed such severe ARIA that they needed to be taken off the drug, at which point they recovered. There were no life-threatening AEs or deaths. The global Alzheimer’s disease market across the eight major markets (8MM: US, France, Germany, Italy, Spain, UK, Japan, and China) is forecast to grow from $2.4bn in 2023 to $19.3bn by 2033, according to GlobalData. GlobalData is the parent company of Clinical Trials Arena .