Alzheimer’s Drug Appears to Slow Symptoms
There could soon be another Alzheimer’s treatment available now that an experimental drug was shown to modestly slow down the disease in people in the early stages of Alzheimer’s.
Donanemab delayed the progression of Alzheimer’s by roughly 35 percent in a clinical trial involving more than 1,700 patients, according to Dr. Daniel Skrovonsky, one of the study’s investigators, who is also director of research and development at Eli Lilly, which manufactures Donanemab.
The trial results were announced in July at the Alzheimer’s Association International Conference in Amsterdam and the study was published in July in the Journal of the American Medical Association (JAMA).
“This is the biggest effect that’s ever been seen in an Alzheimer’s trial for a disease-modifying drug, somewhere in the range of 35 percent slowing of disease progression.” Dr. Skrovonsky said at a press briefing at the conference.
Donanemab is a monoclonal antibody designed to target a protein called amyloid beta, which forms sticky plaques on the brain and can cause brain cells to die. The plaques form in the areas of the brain responsible for memory, learning, perceiving, and reasoning. Researchers and medical professionals maintain that removing plaque buildup is important in disrupting the progression of Alzheimer’s disease.
Phase 3 of Eli Lilly’s clinical trial involved people ages 60 to 85 who were in the early stages of Alzheimer’s, which includes mild cognitive impairment and the mild dementia stage of disease. Participants received either infusions of Donanemab once a month or a placebo for 18 months.
Donanemab produced significant reductions in brain amyloid plaque levels as early as six months after participants started treatment, according to Eli Lilly researchers. Participants were taken off of the drug once the plaques in their brains were mostly gone, which usually occurred within one year. The plaques did not reappear during the study.
In addition, participants who took Donanemab showed a 40 percent less decline on the ability to perform activities of daily living, such as managing finances, driving, engaging in hobbies, and talking about current events.
Besides amyloid, studies have found that abnormal forms of the tau protein can also cause Alzheimer’s disease. So, people with higher levels of tau are considered to be in the advance stages of Alzheimer’s.
In Eli Lilly’s study, Donanemab slowed the progression of the disease by about 17 percent in people with high levels of tau and 35 percent in people with low to medium tau levels. Quite simply, Donanemab was not as effective on participants whose disease was more advanced.
“What we saw is that the ability to slow disease progression was strongest if you catch this disease earlier,” Dr. Skrovonsky said at the conference.
The clinical trial results were welcomed by medical professionals and organizations supporting the 6 million people in the United States with Alzheimer’s, a disease that gradually attacks areas of the brain needed for memory, reasoning, communication, and daily tasks.
Maria C. Carrillo, chief science officer of the Alzheimer’s Association, said these are the strongest Phase 3 data for an Alzheimer’s treatment to date.
“This further underscores the inflection point we are at for the Alzheimer’s field,” Carrillo said in a news release. “The progress we’ve seen in this class of treatments, as well as the diversification of potential new therapies over the past few years, provides hope to those impacted by this devastating disease.”
FDA Approves Lecanemab (Leqembi®) for Alzheimer’s Treatment
Similar to Donanemab, another drug, Lecanemab, was shown to be an effective treatment for Alzheimer’s. However, Lecanemab slowed cognitive and functional decline by 27 percent compared to Donanemab, which delayed progression by about 35 percent.
Nonetheless, the U.S. Food and Drug Administration (FDA) gave traditional approval of Lecanemab in July. The federal agency gave Lecanemab, known by the brand name, Leqembi (pronounced “leh-KEM-bee”) an accelerated approval earlier this year.
Leqembi is manufactured by Eisai and Biogen and has also been shown to slow the progression of Alzheimer’s by targeting amyloid beta. Phase 3 of the clinical trial showed Leqembi delayed cognitive decline by 5.3 months compared to a placebo after 18 months of treatment.
In approving Leqembi on July 7, Teresa Buracchio, acting director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in a news release that this was the “first verification that a drug targeting the underlying disease process of Alzheimer’s disease has shown clinical benefit in this devastating disease.”
The FDA says Lequembi should be prescribed for patients with mild cognitive impairment or mild dementia stage of Alzheimer’s disease, the same population that was studied in the clinical trials. The FDA’s prescribing information recommends caution when considering using Leqembi in patients who take anticoagulants because of the risks of causing intracerebral hemorrhages.
In addition, the federal agency recommends doctors test patients for the genetic mutation, APOE4, the strongest risk factor gene for Alzheimer’s disease. Patients with APOE4 are at greater risk of swelling and brain bleeds if they take Leqembi.
After receiving FDA approval, Medicare announced that it would cover Leqembi’s cost of $26,500-a-year so that more Medicare recipients can have access to the drug.
Chiquita Brooks-Lasure, administrator for the Centers for Medicare and Medicaid Services, said the FDA’s approval is “welcome news for the millions of people in this country and their families who are affected by this debilitating disease.”
While Leqembi and Donanemab have shown promise, scientists and medical professionals warn that both drugs carry serious risks of swelling and bleeding in the brain. In the Donanemab study, these side effects were linked to three deaths.
“These side effects should not be taken lightly,” Dr. Liana Apostolova, one of the study’s investigator and a professor in Alzheimer’s Disease research at Indiana University School of Medicine, told Reuters.
After announcing the results in July, Eli Lilly applied to the FDA for full approval of Donanemab, and said it expects the federal agency to make a decision by the end of the year.
Source Links:
https://www.cbsnews.com/news/eli-lilly-alzheimers-donanemab-trial-stock-up/?ftag=CNM-00-10aac3a
https://investor.lilly.com/news-releases/news-release-details/lillys-donanemab-significantly-slowed-cognitive-and-functional
https://www.npr.org/transcripts/1188075646
https://www.npr.org/sections/health-shots/2023/07/17/1188075646/donanemab-experimental-alzheimers-drug-outperforms-lecanemab-leqembi
https://www.reuters.com/business/healthcare-pharmaceuticals/lilly-drug-slows-alzheimers-by-60-mildly-impaired-patients-alzheimers-group-says-2023-07-17/
