When experimental anti-amyloid antibodies from Eli Lilly and Roche failed to improve symptoms of Alzheimer’s disease in a phase 2/3 study led by Washington University School of Medicine and reported last year, it raised serious doubts about the future of the medicines. But analysis of the trial continued, and, now, the study leaders say they have evidence that one of the drugs—Roche’s gantenerumab—could help a subset of patients.
In trial participants with dominantly inherited Alzheimer's disease (DIAD), which causes early onset of memory loss and other symptoms, Roche’s drug lowered biomarkers of the disorder and neurodegeneration in the brain, Washington University said in a study published in Nature Medicine.
The study did not show evidence of a cognitive benefit to people with DIAD, though it was not designed to measure the cognitive impact of gantenerumab on people who started taking the drug before they developed symptoms. Washington University has now launched an extension of the study, which will allow patients on Roche’s drug to continue taking it and to have their symptoms monitored over time.
Patients in the original trial were randomized to receive either Lilly’s solanezumab, Roche’s drug or a placebo and then tracked for up to seven years. The 52 patients who took gantenerumab showed a reduction of amyloid plaques in the brain—a hallmark of Alzheimer’s—and lower amounts of another culprit protein, tau, the researchers reported.
The investigators also measured a key marker of neurodegeneration: rising levels of neurofilament light chain in the spinal fluid. Gantenerumab seemed to slow the increase of that marker, they said.
After the top-line findings of the phase 2/3 study of solanezumab and gantenerumab were first released, Roche made it clear it had no intentions of giving up on its anti-amyloid antibody, even though Lilly had thrown in the towel on solanezumab in 2016.
Now, the amyloid hypothesis of Alzheimer’s is undergoing a renaissance of sorts, thanks to Biogen’s Aduhelm, an amyloid-fighting drug that was recently approved by the FDA with a broad label in spite of widespread doubts about its efficacy and some loud protests over its $56,000 list price.
Still, there are signs of some enthusiasm in the medical community about trying an anti-amyloid approach in Alzheimer’s before patients see an eruption of major cognitive symptoms. Analysts at Jefferies said last week that they surveyed doctors and found 35% of them have a strong interest in prescribing Aduhelm to Alzheimer’s patients with mild symptoms.
The Washington University study of Roche’s gantenerumab is being supported by the company and several funders, including the Alzheimer’s Association and the National Institutes of Health. The study recruited patients who had a rare genetic mutation that causes the early onset of Alzheimer’s dementia and who had already started showing symptoms like memory decline.
The biomarker readings from the study “suggest that gantenerumab had a favorable impact on the target and downstream markers of Dominantly Inherited Alzheimer's Disease," said Rachelle Doody, M.D., Ph.D., chief of neurodegeneration at Roche and Genentech, in a statement.
Trial director Randall J. Bateman, M.D., professor of neurology at Washington University, added that although the study focuses on people with a genetic predisposition to early Alzheimer’s, the results from the extension arm could be relevant to the future treatment of people with more common forms of the disease.
“The destructive molecular and cellular processes in the brain are similar in both types of the disease,” Bateman said in the statement.