Eli Lilly’s experimental Alzheimer’s drug, remternetug, has shown promising results in lowering levels of brain plaque in patients in the earliest stages of the disease, according to initial data.
A higher dose of remternetug demonstrated a more significant effect in clearing amyloid plaque, as presented during a conference in Sweden on Friday.
Amyloid is a protein that accumulates in the brains of Alzheimer’s patients, disrupting cell function.
Researchers believe that the buildup of amyloid plaque is a critical first step towards the cognitive decline associated with Alzheimer’s disease.
This early data marks a significant milestone in Eli Lilly’s ongoing effort, spanning decades, to develop an Alzheimer’s drug.
Remternetug follows the company’s previous drugs, donanemab and the unsuccessful solanezumab.
While remternetug and donanemab target plaque deposited on the brain, solanezumab focused on the kind that floats in brain fluid.
The remternetug trial included 41 patients in the early stages of Alzheimer’s disease. These patients were randomized to receive either a placebo or remternetug in various doses every four weeks.
Eli Lilly reported that the drug resulted in a “rapid and robust” clearance of amyloid plaque. This clearance is defined as reducing the level to 24.1 centiloids or less, a unit used to measure amyloid in the brain.
The company noted that plaque levels were “dose-dependent,” with the majority of patients receiving the three highest doses of remternetug achieving amyloid plaque clearance by day 169 of the study.
Eli Lilly, based in Indianapolis, is conducting an ongoing phase three trial on remternetug, though the company did not specify which dose sizes are being studied. Completion of this trial is expected in 2025.
The results suggest that remternetug “may provide more robust plaque removal” than donanemab, according to J.K. Wall, an Eli Lilly spokesperson.
A phase two trial of donanemab found that 40% of participants treated with the drug achieved amyloid clearance as early as six months, or around 182 days, after starting the treatment.
However, Wall noted that it is too early to make quantitative comparisons between the two drugs.
Akash Tewari, an equity analyst at Jefferies, also observed “hints of faster amyloid clearance with remternetug vs donanemab” in a note on Friday.
However, Tewari cautioned that it remains uncertain whether amyloid plaque clearance will result in clinical benefits such as reduced cognitive decline.
He pointed out that while some research has shown a causal relationship between plaque removal and the rate of cognitive decline, this has not been consistently supported by donanemab’s data.
Tewari also compared the safety profiles of the two drugs, estimating that remternetug might show similar or higher rates of a problematic brain swelling side effect known as amyloid-related imaging abnormality (ARIA), compared to donanemab.
Eli Lilly observed ARIA in 10 out of 24 patients who received remternetug, with one patient discontinuing the treatment due to a serious adverse event.
ARIA has also been a concern for similar Alzheimer’s drugs from other companies, such as Leqembi from Biogen and Eisai. These companies expect the Food and Drug Administration to grant full approval of Leqembi by the summer.
According to the Alzheimer’s Association, an estimated 6.7 million Americans aged 65 and older are currently living with Alzheimer’s. By 2050, this number is projected to nearly double to almost 13 million.
The association also noted that one in three seniors dies with Alzheimer’s or another form of dementia, which causes more deaths than breast cancer and prostate cancer combined.
