Trial Shows Synthetic Antibody Slows Cognitive Decline

(NIH.gov)

31 Aug. 2021. Results show a synthetic antibody reduces the rate of cognitive decline, one of two measures in a clinical trial of patients with mild to moderate Alzheimer’s disease. The findings were released today by AC Immune SA in Lausanne, Switzerland, developer of the monoclonal antibody semorinemab in partnership with biopharmaceutical company Genentech, and are not yet peer-reviewed.

AC Immune develops diagnostics, vaccines, and treatments for Alzheimer’s disease and other neurodegenerative disorders. Alzheimer’s disease is a progressive neurodegenerative condition, the most common form of dementia affecting growing numbers of older people worldwide. People with Alzheimer’s disease often have deposits of abnormal substances in spaces between brain cells, known as amyloid-beta proteins, as well as misfolded tangles of proteins inside brain cells known as tau. Data from World Alzheimer Reports show in 2020 an estimated 50 million people worldwide with dementia, a number expected to grow to 152 million by 2050.

AC Immune uses two separate technologies to address misfolded proteins, particularly tau that builds up inside neurons in the brain, and spreads between cells, and amyloid-beta proteins that accumulate as plaques outside of neurons. One of those technologies, called SupraAntigen, is the basis for treatments that generate antibodies in the immune system for attacking and breaking up tau deposits, particularly before they cause irreversible damage to neurons.

Semorinemab, says AC Immune, is designed to bind to a specific area of tau proteins called the N-terminus. This area of the tau chemistry is believed to play a role in regulating and stabilizing the protein, thus helping to slow the spread of tau deposits in the brain.

44 percent less cognitive decline

The mid-stage study enrolled 272 participants diagnosed with mild to moderate Alzheimer’s disease at 43 locations in the U.S. and Europe. Genentech, a subsidiary of drug maker Roche in South San Francisco, is conducting the trial. Participants were randomly assigned to receive infusions of semorinemab or a placebo every two weeks for the first three doses, then every four weeks after that. Genentech is extending the trial, offering semorinemab to all participants in an open-label extension, following the placebo-controlled part of the study.

The study team is looking primarily for changes in standard rating scales of cognitive decline and and daily functioning among people with Alzheimer’s disease. On one scale, the 11-item Alzheimer’s Disease Assessment Scale, Cognitive Subscale, semorinemab recipients show less cognitive decline by 44 percent, than placebo recipients, after 49 weeks from beginning the study. On the second measure, the Alzheimer’s Disease Cooperative Study-Daily Living Inventory, researchers report no difference between semorinemab and placebo recipients after 49 weeks. AC Immune says semorinemab is well tolerated and shows no unanticipated safety signals.

While initial findings are mixed, the company says results so far are encouraging. Andrea Pfeifer, CEO of AC Immune, notes in a company statement that “this is the first time a monoclonal antibody has had a therapeutic impact on cognition in the mild-to-moderate AD patient population. Nevertheless, despite these interesting results, we are still cautious about what this may mean for patients as there was not an impact on the rate of functional decline or other efficacy endpoints.”

AC Immune says the trial’s open-label extension may provide more data to assess semorinemab’s effects on patients. The company says it plans to submit the results for presentation at the Clinical Trials on Alzheimer’s Disease meeting in November.

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