- An experimental Alzheimer’s disease drug, donanemab, slowed the progression of symptoms in people with early forms of the disease.
- This follows the FDA’s full approval earlier this month of a similar drug, lecanemab.
- Both drugs are monoclonal antibodies that target the beta-amyloid protein that is involved in Alzheimer’s disease.
Another drug capable of slowing the progression of Alzheimer’s disease may soon be available in the United States.
An experimental drug, donanemab, slowed the progression of symptoms in people with early forms of the disease, according to results of a phase 3 clinical trial.
However, side effects included potentially life-threatening swelling and bleeding in the brain.
This follows the Food and Drug Administration’s full
Both drugs are monoclonal antibodies that target the
Scientists think that reducing the level of beta-amyloid may slow the progression of the disease.
Healthline spoke to three experts about what these drugs may mean for the treatment of Alzheimer’s disease, which currently affects an estimated 6.7 million American adults ages 65 and older, according to the Alzheimer’s Association.
The phase 3 clinical trial for donanemab included 1,736 people with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease.
MCI is an early form of memory loss or loss of other cognitive functions, such as language or visual/spatial perception. It can be a precursor to Alzheimer’s disease, although some people with MCI see improvement in their symptoms.
Brain scans confirmed that all participants in the clinical trial had brain deposits of beta-amyloid and tau — another protein involved in Alzheimer’s disease.
Participants were randomly assigned to receive either donanemab or an inactive placebo. These were given every four weeks by intravenous infusion for about 18 months.
The results showed that cognitive function and daily functioning continued to decline in all participants throughout the study.
However, those receiving donanemab saw a delay in that decline of about 4 months, researchers found.
When researchers looked only at people with low or medium levels of tau, those taking donanemab saw a delay in that decline of about 8 months.
Participants with high levels of tau had little to no benefit from the drug, the study found.
In addition, people who took donanemab were less likely to progress from MCI to mild dementia — which means moving from being fully independent during daily activities to requiring some assistance, the authors of a related
They were also less likely to move from mild dementia to moderate dementia — needing some assistance with basic self-care, according to the editorial’s authors.
The results of the trial also showed that there were some potentially life-threatening side effects of the drug.
Almost 37% of people who received donanemab developed swelling or bleeding in the brain, compared to 15% of those who received the placebo. Most cases in the donanemab group were mild to moderate, although three participants died as a result.
Eli Lilly said it has filed for FDA approval of donanemab, and hopes to hear from the agency by the end of the year.
The phase 3 clinical trial for lecanemab showed similar benefits for people with MCI or mild dementia, with a slowing of the decline in cognition and daily functioning.
This drug was also associated with potentially life-threatening swelling and bleeding in the brain. As a result, the FDA required the prescribing information for Leqembi to include a boxed warning about these risks.
Dr. Doug Scharre, director of the division of Cognitive Neurology at the Ohio State University’s Wexner Medical Center’s Neurological Institute, said the “big news” about lecanemab and donanemab is that they not only improve people’s symptoms, but they also alter the course of the disease.
However, he emphasized that the clinical benefits seen during the first year-and-a-half of treatment — the length of the phase 3 trials for these drugs — were “modest.”
“It is possible that benefits may persist for longer periods,” he told Healthline, “but we will have to wait and see.”
With both drugs, though, there was a significant delay in declines of cognition and daily functioning, compared to the placebo group, said Dr. Christian Camargo, an assistant professor at the University of Miami Miller School of Medicine and a neurologist at UHealth — University of Miami Health System.
For patients, this translates to “time saved,” he told Healthline, meaning additional time with better functioning.
“If you need less assistance with day-to-day activities and you can still enjoy conversations and activities, that likely reflects on quality of life,” said Scharre.
Dr. Manisha Parulekar, co-director of Hackensack University Medical Center’s Center for Memory Loss & Brain Health, agreed.
With these drugs, “you are able to maintain your functioning for an additional six months without needing help from your family or any other people,” she told Healthline. “This helps you live independently for that extended period of time.”
While the results of the trials for these treatments are promising, Camargo pointed out that Alzheimer’s disease is very complex.
“People often have multiple pathologies present, and the proteins that accumulate and damage the brain as a result of Alzheimer’s disease tend to re-accumulate,” he said.
Given the complexity of the disease, Parulekar thinks anti-amyloid drugs are unlikely to be the only treatment needed for Alzheimer’s disease.
Still, “this group of medications has given us that next step,” she said, “but we have to keep building on these developments.”
The modest benefits and the potential risk of serious side effects mean that decisions about using these drugs will remain a “highly personalized and individual decision,” said Camargo, requiring discussions between patients and their doctor.
This, he said, will need to take into account the person’s genetic profile and other risk factors.
Parulekar said use of these drugs will also require careful patient selection, and ongoing monitoring for possible side effects such as swelling or bleeding in the brain.
In addition, these treatments work best in the early stages of the disease, she pointed. They are not designed for people with late-stage mild, moderate or severe dementia.
Unfortunately, “a lot of times people may not go to the doctor earlier on,” she said. “So by the time they seek a diagnosis, they may very well be into the later mild or moderate stage of dementia.”
Scharre said to improve treatment outcomes, health care providers need to be knowledgeable about how to diagnose Alzheimer’s disease in the early stages.
Also, “if you or a loved one has noticed a change in your thinking or memory over the last year, you should get to your primary care provider for evaluation,” he said.
Ohio State University has developed a self-administered test designed to detect early signs of cognitive, memory or thinking impairments. This is free of charge and can be taken at home or in your provider’s office.
Camargo, who provides specialized dementia care to a socioeconomically and racially diverse community, said ensuring access to new treatments for Alzheimer’s disease is of particular concern to him.
But many factors may limit the reach of these drugs.
For example, in some multi-generation households in certain communities, older adults continue to work to help support their family, he said. As a result, it may be difficult for them to go to the clinic regularly for infusions — monthly for donanemab and twice a month for Leqembi.
They also may face other barriers to treatment, such as a lack of a driver’s license or access to a vehicle or public transportation.
Cost is another issue that may prevent certain people from accessing these treatments.
The annual price for Leqembi is $26,500. Medicare has agreed to cover this drug, reports Kaiser Family Foundation, but with a 20% coinsurance payment. This amounts to more than $5,000 out-of-pocket each year.
That may be out of reach for some people on Medicare, in particular for older Hispanic and Black adults, who have
In addition, while the majority of people with Alzheimer’s disease are 65 years or older, preclinical cognitive changes or mild cognitive impairment can occur in younger people, said Parulekar.
These people may not have Medicare, which is mainly for people 65 and older.
Currently, the only other insurance to cover Leqembi is the Veteran’s Administration’s program, although that excludes people younger than 65.
So middle-aged people who might benefit from these new drugs may not have coverage through their health insurance, or they may be uninsured or underinsured.
“Unfortunately, this [lack of coverage for younger ages] is going to impact health equity and access to treatments for people in a diverse population,” said Parulekar.
For the first time, there may soon be two drugs that can help slow Alzheimer’s disease symptoms. Experts caution that the benefits may be modest.