A new Alzheimer’s drug delivered strong results in its phase 3 trial, slowing cognitive decline by 35%, but the risk of a potentially deadly side effect could make getting FDA approval challenging.
The challenge: Alzheimer’s is an incurable, progressive, and deadly brain disease characterized by problems with memory and cognition. More than 6 million people in the US live with the disease, and it kills around 120,000 people each year, making it one of the country’s top 10 causes of death.
Despite decades of research, our ability to treat Alzheimer’s is still extremely limited.
Alzheimer’s one of the top 10 causes of death in America.
In the US, the FDA has approved just five Alzheimer’s medications: three treat only the symptoms of the disease, while one removes the toxic plaques that build up in the brain but doesn’t clearly slow cognitive decline.
The fifth medication slowed cognitive decline in a phase 3 trial, but the FDA is still reviewing that data to decide whether to grant the med full approval (it’s currently granted conditional “accelerated” approval).
The idea: Years before people start experiencing symptoms of Alzheimer’s, their brains can show signs of the disease, including improperly folded tau proteins and amyloid plaques, which are clumps of proteins that build up between neurons.
Pharmaceutical company Eli Lilly’s new Alzheimer’s drug, donanemab, is also an antibody that binds to proteins in amyloid plaques. The goal is to trigger the immune system to attack and destroy the plaques, clearing them from the brain and slowing disease progression — and it seems to work as hoped.
The study: On May 3, Eli Lilly shared data from TRAILBLAZER-ALZ 2, a randomized, double-blind phase 3 trial. The study involved 1,182 people with clinical symptoms of Alzheimer’s and intermediate levels of tau proteins in their brains, suggesting that their disease was still in the early stages.
After giving some trial participants donanemab and others a placebo, the researchers measured their cognitive decline over the next 18 months — and found that the new Alzheimer’s drug slowed it by 35%, compared to people in the placebo group.
“We are extremely pleased that donanemab yielded positive clinical results with compelling statistical significance for people with Alzheimer’s disease in this trial,” said Daniel Skovronsky, Eli Lilly’s chief scientific and medical officer.
“This is the first phase 3 trial of any investigational medicine for Alzheimer’s disease to deliver 35% slowing of clinical and functional decline,” he continued.
Eli Lilly has yet to publish the results of the trial, but says it has submitted the data to a peer-reviewed journal and plans to present the results at the Alzheimer’s Association International Conference in July.
Risks and caveats: When a group of 552 people with high levels of tau in their brains — suggesting that their Alzheimer’s was more progressed — was added to the initial population, the impact of the drug wasn’t quite as pronounced, with cognitive decline slowing by just 22%.
Two participants died from side effects during the trial.
The drug also carries a serious safety risk: antibodies designed to clear amyloid plaques from the brain have been shown to cause amyloid-related imaging abnormalities (ARIA), including temporary brain swelling (ARIA-E) and microhemorrhages (ARIA-H).
According to Eli Lilly, 24% of treated participants — including both the low and high tau groups — experienced brain swelling, and 31.4% experienced microhemorrhages.
While most of the cases were mild to moderate, 1.6% of the treated participants had serious cases of ARIA, and two died from it (a third died after experiencing serious ARIA, although their death was not explicitly linked to it).
Looking ahead: Skovronsky told CNBC he believes the benefits of the new Alzheimer’s drug outweigh the potential risks of ARIA, but first it’ll be up to the FDA to weigh those costs and benefits.
Eli Lilly plans to submit data to the agency before July and says it will work with regulators to get the medication approved as quickly as possible.
“Every day that goes by, there are some patients who pass through this early stage of Alzheimer’s disease and become more advanced and they won’t benefit from treatment,” Skovronsky told CNBC. “That’s a very pressing sense of urgency.”
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