Alzheimer’s patients now have more options than ever for treating their disease— two drugs are approved to treat the causes of Alzheimer’s, and the U.S. Food and Drug Administration is currently considering approving another, which could be available next year. Many researchers are starting to focus on how to get the most out of these treatments: how to identify people who will benefit the most, how long people need to be treated, and how to measure the effect of the drugs. They are also exploring whether these drugs could not only slow, but maybe even prevent some of the more damaging effects of the disease.
At the annual Clinical Trials on Alzheimer’s Disease conference in Boston, Eisai and Biogen, makers of the most recently approved drug, lecanemab (Leqembi), as well as Eli Lilly, maker of donanemab, which the U.S. Food and Drug Administration (FDA) is currently reviewing for possible approval by the end of the year, reported on their latest studies. Eisai provided additional data on longer-term use of its drug, as well as on a new formulation that would make it easier for patients to take than the current hour-long IV infusion once every two weeks. Lilly shared new data from its final phase of testing that showed patients’ ability to execute daily tasks improved, as did their performance on memory, orientation, and judgment tests while taking the experimental drug, compared to those receiving a placebo.
The FDA approved lecanemab in January, based on data showing that IV infusions once every two weeks for a year and a half delayed cognitive decline by 27% in those receiving the drug compared to people getting a placebo. At the Boston conference this week, Eisai presented encouraging data on a new formulation of its drug—one that doctors or patients themselves can inject once a week rather than receive through an hour-long infusion once a month. In a group of 72 patients who received lecanemab for the first time as an injection, and 322 patients from the original study who switched from the IV infusion to the injections for six months, PET scans showed that the injections led to a 14% greater reduction in amyloid compared to those who had received IV infusions after six months. That, according to Eisai, may be because the injections result in a higher blood concentration of the drug by about 11% compared to the IV infusion. “We think the [injection] formulation will really help patients in terms of making it more convenient and not having to go to infusion centers,” says Dr. Michael Irizarry, senior vice president of clinical research at Eisai. He says the company plans to request that the FDA approve the injections by the end of March 2024.
Eisai also provided more detailed and extended data suggesting that lecanemab works best when it is used as early in the disease as possible, and that the benefits continued to 24 months, six months beyond the original study.
Experts believe that tau, which forms tangles that can compromise brain neurons, tends to accumulate after amyloid plaques have caused damage, so people with low levels of tau are still at the relatively early stages of disease. In Eisai’s latest study, researchers looked at a subset of the patients in the company’s original study who had very low levels of tau. In this group, 76% of those getting lecanemab showed no decline in tests of memory, orientation, or judgment; or in their engagement in social activities and hobbies; or in their personal care habits compared to 55% of those getting placebo. Even more encouraging, among these people with early disease, 60% of those getting the drug showed improvement in their test scores compared to 28% in the placebo group.
“This supports starting earlier in treatment for people who have symptomatic Alzheimer’s in order to maintain or improve their cognitive function,” says Irizarry.
Lilly saw similar benefits in early-stage patients who received its experimental drug, donanemab. In its study, all patients received tau PET scans, so the researchers could distinguish between those at earlier and later stages of disease. Among people with low-to-medium amounts of tau in the brain, 36% of those receiving the drug showed slowing of disease progression as measured by tests of memory, orientation, judgment, and measures of social engagement.
Delaying the onset of symptoms is essential—not just for patients, who can remain independent for longer, but for their caregivers as well. Lilly’s data showed that most patients in the study who were taking donanemab were able to remain at the same level of dependency at which they started the trial—for most that meant they needed some reminders about daily activities, such as taking their medicine or putting out the trash or other housekeeping tasks. But they didn’t progress quickly into more dependent stages in which they would need help getting dressed, remembering to eat, and executing other critical skills. In fact, about a quarter of the people taking the drug did not move on to becoming more dependent, compared to 50% of those taking placebo during the 18 month study.
Both Eisai’s and Lilly’s data confirm that starting treatment earlier gives the medications more opportunity to clear amyloid build up and prevent damage to brain neurons. That means it might even be possible to not only delay some of the more advanced symptoms of Alzheimer’s related to memory and cognition, but to also prevent them. Dr. John Sims, senior medical director at Lilly, says that the company anticipates that donanemab will not be a life-long prescription—but that patients could use it to either remove or reach an acceptable level of amyloid in the brain, which can then be monitored as they come off the drug for periods of time. “The hypothesis we are working on is that it’s much better to monitor the disease because it is a really slow process overall, and maybe some people may never need another treatment,” he says. If these results are supported by continued follow up, that would mean focusing even more on how best to diagnose patients at the earliest stages of disease, before memory or other cognitive symptoms appear. “The data show that the most optimal benefit occurs if people are treated as early as possible,” says Irizarry.
Experts in the field are already working on honing the criteria for diagnosing Alzheimer’s, and developing guidelines for even non-dementia experts such as primary care physicians to make it easier to distinguish when people have the condition, and which patients would benefit from treatment—as early as possible.Leave a comment