- More than 55 million people globally have dementia, with Alzheimer’s disease contributing to 60%-70% of cases.
- Phase 3 clinical trial results shared in a press release suggest a new drug called lecanemab helps slow the cognitive decline rate in Alzheimer’s patients by 27% after 18 months of treatment.
- The investigators expect the U.S. medicines regulator to make a decision about the new drug by early January 2023.
Now, Phase 3 clinical trial results for a new drug called lecanemab suggest that the medication could help slow the rate of cognitive decline of people with early Alzheimer’s disease by 27% after 18 months of treatment.
Lecanemab is an investigational humanized
According to Dr. Sharon Cohen, a neurologist and medical director of the Toronto Memory Program in Toronto, Canada, and part of the investigation team for the Phase 3 clinical trial, lecanemab is an antibody that is given by intravenous infusion and works by clearing amyloid from the brain.
“Amyloid is a toxic protein that accumulates early in Alzheimer’s disease and is responsible, not only for direct injury to brain cell function but also leads to a cascade of other toxic processes that further injure the brain,” she explained to Medical News Today.
“When amyloid is cleared by lecanemab early in the disease, the disease progresses more slowly allowing individuals to maintain their cognition and independence for a longer time,” Dr. Cohen added.
Amyloid, also known as beta-amyloid protein, is a sticky substance that if left alone, forms plaques in the brain. These plaques disrupt communication between brain cells. Past research shows greater plaque buildup is linked to greater memory loss.
“The topline results of the Clarity study showed 27% slowing of disease on the primary clinical endpoint for those treated with lecanemab and this was highly statistically significant.”
— Dr. Sharon Cohen
Dr. Cohen said that currently approved Alzheimer’s disease medications that are available in most countries treat symptoms only and do not impact the underlying early brain changes of the disease.
“As such, these medications work relatively late in the disease and do not stabilize or slow down brain cell destruction nor related loss of function. Furthermore, the benefit of the currently available symptom treatments is very modest,” she detailed.
“Finally, current symptom treatments are not approved for the pre-dementia stage of Alzheimer’s disease, and therefore [most] individuals with mild cognitive impairment due to Alzheimer’s disease get substantially worse before they are eligible for these treatments,” Dr. Cohen continued.
“This is, of course, counter to the principle of early initiation of treatment being desirable for a slowly progressive disease,” she added.
According to Dr. Scott Kaiser, a geriatrician and director of geriatric cognitive health for the Pacific Neuroscience Institute in Santa Monica, CA, for a long time, there were no medications to treat Alzheimer’s disease.
“Then we had medications that could help treat symptoms, but there hasn’t been any disease-modifying medication — anything that could actually treat the underlying pathology and slow the progression of the illness,” he said.
Then Dr. Kaiser said the drug aducanumab was discovered.
“Aducanumab … was one of these first monoclonal antibodies targeting sub-parts of this beta-amyloid,” he said.
“[Aducanumab] was really controversial because when aducanumab came out and went through FDA review, their studies … definitively showed that these drugs were good at clearing amyloid, but they weren’t able to definitively show that this had a clinical impact. It’s one thing to clear these plaques out of the brain, but it’s another to actually improve people’s thinking, functioning, and overall lives,” he elaborated.
“[With the Phase 3 clinical trial results for lecanemab] it appears that there’s an impact on the underlying pathology and some positive clinical impact for people who have mild cognitive impairment for early Alzheimer’s disease. And that’s a paradigm shift — that’s really an exciting new direction.”
— Dr. Scott Kaiser
“Now, experts (will) debate — how meaningful is that ‘clinical impact’? If you can show a small change on a complex scale, that might be numerically significant. But is it really significant in terms of people’s health, well-being, function, (and) quality of life? There’s going to be a robust debate going forward,” he added.
According to Dr. Cohen, lecanemab can cause a side effect known as
“This is a side effect common to most anti-amyloid antibodies and is seen mainly on MRI brain scans. There are two types of ARIA: ARIA-E which refers to edema or swelling in the brain; and ARIA-H which refers to microscopic bleeding,” she explained.
“Importantly, the rate of ARIA with lecanemab is low — 12.5% for ARIA-E and 17% for ARIA-H. And in most cases of ARIA there are no symptoms — symptoms occur in only 2.8% with ARIA-E and in only 0.7% with ARIA-H. Furthermore, ARIA usually resolves spontaneously and can be managed and monitored.”
— Dr. Sharon Cohen
Medical News Today also spoke with Dr. Ronald Petersen, a neurologist and director of Mayo Clinic’s Alzheimer’s Disease Research Center, about possible side effects of lecanemab. He also mentioned the ARIA-E brain swelling.
“Many of those patients, however, did not experience any related symptoms,” he said. “The prevalence of the side effects was lower than in similar experimental drugs. With monitoring by a physician, these side effects appeared to be manageable,” he told MNT.
According to Dr. Cohen, Phase 3 clinical trial results will be presented at the Clinical Trials on Alzheimer’s Disease Congress (CTAD) in November 2022, with publication in a peer-reviewed medical journal to follow.
“The FDA has agreed that the Clarity study will serve as the confirmatory trial for lecanemab in individuals with mild cognitive impairment and mild dementia due to Alzheimer’s disease. The FDA will render a decision on lecanemab approval by Jan. 6, 2023,” she added.
Dr. Cohen also mentioned multiple other studies with lecanemab are underway to develop additional treatment options, including:
- being studied in the AHEAD 3-45 trial, a Phase 3 Alzheimer’s prevention trial for cognitively normal individuals with preclinical Alzheimer’s disease;
- examining a subcutaneous formulation that may allow greater ease of delivery compared to the intravenous formulation;
- used as a background anti-amyloid agent for use in combination with an anti-tau investigational drug in the Dominantly Inherited Alzheimer Network Tau NexGen platform study.
Dr. Mary Sano, director of the Alzheimer’s Disease Research Center, professor in the Department of Psychiatry, and associate dean for clinical research at Mount Sinai School of Medicine, told MNT she was happy to see a drug reach all of its proposed primary and secondary endpoints.
However, she stated a full report will be important to fully understand the safety of lecanemab.
“Also, the current medication is delivered via an infusion every two weeks, which can be quite burdensome. It will be important to explore ways to get the most effective and cost-efficient delivery system,” Dr. Sano added.
Dr. Petersen stated the news about lecanemab is “very good news” for patients with Alzheimer’s disease and their families.
“While this is not a cure for the disease, it represents a step in the right direction by slowing cognitive decline. These data suggest that we can intervene in the amyloid process and slow it down. Now, we need to move earlier in the disease process to treat people who are amyloid positive but clinically normal.”
— Dr. Ronald Petersen
Dr. Kaiser also called the Phase 3 clinical trial results “positive” and “encouraging.” However, he said there may be controversy in the day ahead with differing expert opinions, as well as debates regarding the potential costs of lecanemab and how to ensure fair and equal access.