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November 15, 2022

The long-awaited trial results of Roche's Alzheimer's drug

Daily Briefing

    Gantenerumab, an experimental Alzheimer's drug developed by Roche Holding AG, failed to significantly slow cognitive decline in people with early Alzheimer's, according to two new studies.

    Study details

    The two late-stage trials, called Graduate I and Graduate II, involved 2,000 participants and lasted 27 months.

    In the studies, participants were randomized into equal-sized groups and given either a 1,020 mg injection of gantenerumab or an injection of a placebo. Similar to other drugs like Aduhelm, gantenerumab targets accumulations of the beta-amyloid protein, a protein found in the brains of Alzheimer's patients and is believed to be linked to the disease.

    In the trials, researchers measured participants' cognitive decline based on their performance on an 18-point measure of memory and cognition called the Clinical Dementia Rating scale—Sum of Boxes.

    In one of the trials, gantenerumab reduced cognitive decline by 8%, and in the other trial by 6%. However, neither result passed the threshold for statistical significance, Roche said.

    Brain swelling, which is a common side effect in drugs that lower amyloid proteins, was reported in a quarter of participants in both studies, Roche said.

    More detailed study results will be released on Nov. 30.


    In a statement, Roche's CMO, Levi Garraway, said the results of the trial were disappointing. "So many of our families have been directly affected by Alzheimer's, so this news is very disappointing to deliver," Garraway said. "We are profoundly grateful to the study participants, their care partners and study sites for their contributions to this research."

    Rachelle Doody, global head of neurodegeneration at Roche, said that while the trials were unsuccessful, they bolstered the theory that beta-amyloid proteins are related to Alzheimer's symptoms since both trials showed a reduction in cognitive decline.

    Drugs reducing beta-amyloid proteins will likely continue to play a role in fighting Alzheimer's, Doody said, though they'll likely work in combination with other therapies.

    "We will be showing that there is a relationship between the lowering of amyloid and the clinical outcomes," she said. "It's just that when you don't get the amyloid lowering that you expected you won't get the clinical outcome that you expected."

    Doody added that Roche will end trials of gantenerumab in populations with early Alzheimer's but is still testing it as a preventive treatment in people who are at high risk of developing the disease and will make a decision on those trials in the future. Roche is also testing an additional version of gantenerumab that is better at accessing the brain.

    In a statement, the Alzheimer's Association said it was disappointed by the trial results but that the trials will further contribute to the understanding of Alzheimer's.

    "Although the drug did not meet its primary endpoint, the trials further illustrate the relationship between removal of beta-amyloid and reduction of clinical decline," the statement said.

    The Association added that research on beta-amyloid drugs should continue.

    "We know that current anti-amyloid approaches are not a cure, nor will they stop the disease on their own, but they are the first wave of effective treatments for Alzheimer's, with more to come," the statement said. (Roland, Wall Street Journal, 11/14; Burger, Reuters, 11/14; Feuerstein/Garde, STAT+ [subscription required], 11/14; McGinley, Washington Post, 11/14)

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