Two experimental drugs failed to prevent or slow mental decline in a study of people who are virtually destined to develop Alzheimer’s disease at a relatively young age because they inherited rare gene flaws.
The results announced Monday are another disappointment for the approach that scientists have focused on for years — trying to remove a harmful protein that builds up in the brains of people with Alzheimer’s, the leading cause of dementia.
“We actually don’t even know yet what the drugs did” in term of removing that protein because those results are still being analyzed, said study leader Dr. Randall Bateman, professor of neurology at Washington University in St. Louis.
But after five years on average, the main goal of the study was not met — people on either of the drugs scored about the same on thinking and memory tests as others given placebo treatments.
More than 5 million people in the United States and more than 40 million worldwide have Alzheimer’s. Current drugs only temporarily ease symptoms and do not alter the course of the disease.
The study tested solanezumab by Eli Lilly & Co., and gantenerumab by Swiss drugmaker Roche and its U.S. subsidiary, Genentech. Both drugs gave disappointing results in some earlier studies, but the doses in this one ranged up to four to five times higher and researchers had hoped that would prove more effective.
A rare, genetic form of the disease strikes young and decimates families. But the families, who meet annually at an emotional conference in Chicago, hold the key in discovering drugs that could prevent Alzheimer's disease decades before symptoms start.
The study was funded by the U.S. National Institute on Aging, the Alzheimer’s Association and some foundations.
It involved about 200 people in the United States, Europe and elsewhere with flaws in one of three genes.
“If you get one of these genetic mutations you’re almost guaranteed to get Alzheimer’s,” typically in your 30s, 40s or 50s, said Dr. Eric McDade, another study leader at Washington University.
They also have a 50% chance of passing the mutation on.
While people like this account for only about 1% of Alzheimer’s cases, their brain changes and symptoms are similar to those who develop the disease at a later age. That gives a unique chance to test potential treatments.
“We know everyone will get sick and we know about what time that is” in their lives, Bateman said.
Most study participants already had signs of the harmful protein in their brain even if they were showing no symptoms when the study started.
They were given either a gantenerumab shot, an IV of solanezumab or fake versions of these treatments every four weeks. The drugs made no difference in a combination score of four memory and thinking tests compared to placebo treatments.
Side effects were not disclosed, but “there’s no evidence of any drug-related deaths in the trial,” McDade said.
Details will be given at a medical meeting in April.
Carrie Richardson, 38, of Montgomery, Alabama, has the mutation. She remembers not being able to bring her friends around her father, who died when he was 43.
She enrolled in the drug trial in 2013, and stayed in it until it ended a few months ago, she said Monday, not long after she learned of the study’s disappointing results.
Richardson said she doesn’t regret being involved in the trial.
“I think the doctors are on the right track,” she said. “I’m still optimistic about new drugs and new trials, at least for my kids.”
McDade said researchers have begun preenrolling people for another trial that hopefully will start sometime next year, although the drugs to be tested have not yet been chosen.
“We’re committed to this very rare and devastating form of Alzheimer’s,” he said.
Solanezumab is being tested in another study to see if it can slow memory loss in people with Alzheimer’s.
Gantenerumab also is being tested in two other large experiments that are expected to give results in two to three years.
It’s unclear whether the results will affect views on aducanumab, another experimental drug that makers say can remove the harmful protein and slow mental decline. Results on it have been mixed, and the companies have said they will seek federal approval for it soon. Cambridge, Massachusetts-based Biogen is developing it with a Japanese company, Eisai Co. Ltd.
The Alzheimer’s Association, a health organization focusing on Alzheimer’s care, support and research, said it looked forward to a more complete report at upcoming scientific conferences.
“We learn from every clinical trial,” Maria C. Carrillo, the organization’s chief science officer, said in a statement. “In these findings there will be valuable lessons on how to best conduct clinical trials in people with and at risk for Alzheimer’s, and where to focus our energies moving forward.”
Pursuit of an Alzheimer’s remedy has been marked by more than 100 failures, but researchers continue to make new discoveries.
“Ongoing and continued research and trials will bring us closer to our goal to stop Alzheimer’s,” Bateman said on the university’s website. “We will continue until we are successful.”
Leah Thorsen of the Post-Dispatch and Reuters contributed to this report. The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Department of Science Education.