New Alzheimer’s Drug Donanemab Approved by FDA
Donanemab, an anti-amyloid antibody, was given FDA approval to slow the progression of the disease.
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The drug donanemab (also known as Kisunla™) has been approved by the US Food and Drug Administration (FDA) for the treatment of adults with early symptomatic Alzheimer’s disease (AD).
This marks the second anti-amyloid antibody given full FDA approval to slow the progression of the disease.
Concerns over safety and efficacy delayed approval
Donanemab is an antibody that targets amyloid beta, a protein that is deposited in lumps and plaques in the brains of people with AD. This is a key characteristic of the disease, and the theory that these plaques drive development of the disease – known as the amyloid hypothesis – has become central to AD drug design efforts.
The FDA’s approval follows promising data from the Phase 3 TRAILBLAZER-ALZ 2 study published last year, which found donanemab slowed the rate of decline in patients with early-stage AD by over 20%. The decision was delayed by an expert panel’s additional scrutineering to investigate donanemab’s safety and efficacy.
Slowing disease progression and clearing amyloid
The TRAILBLAZER-ALZ 2 study followed 1,736 participants with early AD who received intravenous infusions of either donanemab or a placebo over 18 months. Participants were further split into different groups depending on levels of a protein called tau – another indicator of AD progression – in their brain.
The researchers first analyzed the overall study population, which included those with low to high levels of tau. In this group, one rating scale (the integrated Alzheimer’s Disease Rating Scale, or iARDS), which measures the severity of AD, found donanemab slowed disease progression by 22% compared to placebo.
The anti-amyloid drug was more effective in people who were less advanced in their disease with low to medium tau levels, the analysis revealed, slowing cognitive decline by 35% on the iARDS scale compared to placebo.
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Subscribe for FREEAlongside slowing the rate of decline, donanemab also effectively cleared amyloid plaques hypothesized to be involved in the thinking and memory problems associated with the disease. In the overall study population, donanemab reduced amyloid plaques on average by 61% at 6 months, 80% at 12 months and 84% at 18 months compared to the beginning of the study.
“Kisunla demonstrated very meaningful results for people with early symptomatic Alzheimer's disease, who urgently need effective treatment options. We know these medicines have the greatest potential benefit when people are treated earlier in their disease, and we are working hard in partnership with others to improve detection and diagnosis,” said Anne White, executive vice president and president of Lilly Neuroscience.
Benefits and risks of anti-amyloids – A balancing act
Donanemab’s approval is the second such development in the landscape of anti-amyloid drugs. Last year, fellow amyloid-targeting antibody lecanemab (Leqembi) was given the green light by the FDA after additional trial data that confirmed its clinical benefit. This permitted lecanemab to be converted from an accelerated to a traditional FDA approval.
However, both drugs have received scrutiny for their potential side effects. Lecanemab, for example, features a boxed warning – the strongest required by the FDA – cautioning users of the risk of potentially dangerous changes in the brain known as amyloid-related imaging abnormalities (ARIA).
AIRA comes in two forms: ARIA-E, related to edema or swelling in the brain, and ARIA-H, small brain hemorrhages or microbleeds. While ARIA does occur in the brains of people with AD who are not taking these kinds of anti-amyloid drugs, trial data suggests that they are more common in those receiving treatment.
Donanemab’s label also warns of the risk of ARIA, with 36.8% of donanemab-treated patients in the TRAILBLAZER-ALZ-2 trial showing at least one type of ARIA, compared to 14.9% in the placebo group.
The most common ARIA symptoms include headache, confusion, vomiting and visual or gait disturbance. In some cases, ARIA can be mild and asymptomatic, though in others it can present serious and even life-threatening complications.
As trial data suggests the drug may be most useful in patients in the earliest stages of AD, the risks of these potentially serious adverse events will have to be weighed against the clinical benefits of slowing the disease’s progression.
At what cost?
The treatment also comes at a significant cost. Each vial is priced at $695.65, amounting to $32,000 for a 12-month course. However, the FDA’s instructions state that treatment can be stopped after scans show amyloid plaques have been removed to minimal levels. This makes donanemab the only amyloid-targeting therapy to use a limited-duration regimen based on plaque removal – and nearly half of the study’s participants with low/medium tau levels completed their course within 12 months.
“Our deepest thanks to the patients and their loved ones for participating in our clinical programs and to Lilly scientists and collaborators persevering over decades of research,” White added. “Each year, more and more people are at risk for this disease, and we are determined to make life better for them.”
