The Alzheimer’s drug crenezumab did not slow or prevent cognitive decline in a long-running study of Colombian families who carried a genetic mutation that put them at near certain risk to develop the mind-robbing disease.
The study of 252 people tested whether the pharmaceutical giant Roche’s antibody crenezumab could slow or halt the disease if participants took the medication before memory or thinking problems surfaced. But the drug did not demonstrate a significant benefit in tests measuring cognitive abilities or memory function among study participants, Roche said Thursday in a news release.
The widely anticipated study that began enrolling patients in 2013 sought to test the idea that Alzheimer’s disease could be prevented or delayed if otherwise healthy people took a medication years before developing memory and thinking problems. To that end, Roche teamed with researchers from Phoenix-based Banner Alzheimer’s Institute and the University of Antioquia in Colombia, who first identified the extended families with a rare genetic mutation that brought on Alzheimer’s disease early, usually when they were in their mid-40s.
Study participants who inherited the genetic trigger, known as the paisa mutation, were randomly assigned to either get the drug or a placebo. Another placebo group included people without the mutation. None of the participants knew their genetic status when receiving the drug or placebo.
Crenezumab is part of a class of antibody drugs designed to counter amyloid beta protein accumulation in the brains of Alzheimer’s patients. Amyloid is one of the known markers of Alzheimer’s, and researchers theorize that if the drug could clear amyloid from people before they developed symptoms, it could delay or halt the disease.
Roche and Banner Alzheimer’s Institute said small differences favoring the drug over the placebo were observed but did not rise to the level of being statistically significant. Roche will release initial data from the trial Aug. 2 at the Alzheimer’s Association International Conference in San Diego.
“We’re disappointed that the treatment did not demonstrate a statistically significant clinical benefit,” said Eric Reiman, Banner Alzheimer’s Institute’s executive director and a study leader. “At the same time, we’re proud of the impact that this precedent-setting trial has had in shaping a new era in Alzheimer’s prevention research, and we’re extremely grateful to our research participants and their families.”
Roche said 94% of study participants completed the trial and received the drug or placebo over the course of five to eight years. No new safety issues were identified over the course of the study, Roche said.
In 2019, Roche previously halted two studies of crenezumab in groups of patients who develop Alzheimer’s later in life. Roche is studying another anti-amyloid drug, called gantenerumab, and expects to report results later this year.
Stephen Salloway, a professor of neurology and psychiatry at Brown University, said the results are disappointing.
“I don’t want to throw the baby out with the bathwater because one drug with one particular target is ineffective,” said Salloway, who also directs a memory and aging program at Butler Hospital in Providence, Rhode Island.
Salloway said the Alzheimer’s researchers are waiting for results from larger studies evaluating other amyloid-targeting drugs. Biogen and Eisai this year expect to report results from a large study of the drug lecanemab. Eli Lilly makes an Alzheimer’s drug called donanemab with late-stage results expected next year. The Food and Drug Administration last year approved Biogen’s Aduhelm following two clinical trials that yielded mixed results.
“I think to pursue prevention trials with amyloid-lowering drugs makes sense,” Salloway said.
Randall J. Bateman, a Washington University professor of neurology, said Alzheimer’s researchers are interested in the Colombian study’s findings because the drug was administered before memory and thinking problems surfaced.
When the data is released, researchers will want to know whether there’s any signal the drug benefited study participants. Researchers also will want to know whether the drug affected amyloid markers such as plaques that build up in the brain or tau, another protein found in Alzheimer’s patients.
“The question really is would it be more effective if we go earlier?” Bateman said. “I think there’s biological reasons to believe it will, but to date, we don’t have any evidence of that.”
Bateman’s team led an international study that evaluated Eli Lilly’s solanezumab and Roche’s gantenerumab in people who carried a mutation that guaranteed early-onset Alzheimer’s disease. Initial results released in 2020 showed neither drug slowed cognitive decline, which was measured by various memory and thinking tests. Bateman said later analysis showed some positive signals for gantenerumab.
Bateman believes larger prevention studies underway will deliver pivotal information about the disease and potential new treatments.
“What’s really gratifying is seeing so many groups launching and implementing prevention trials,” Batemen said. “In the long run, this will have a huge public health benefit.”
Ken Alltucker is on Twitter at @kalltucker, or can be emailed at [email protected]