Alzheimer’s, FDA approves first drug that acts against amyloid plaque in the treatment of early symptomatic disease

We are still far from a real “cure” for Alzheimer’s disease, the most widespread cause of dementia, of which six out of 10 patients suffer from itthat is, approximately 60 percent of the 55 million cases currently registered in the world.
But scientific research is beginning to show significant progress in the fight against neurodegenerative disease which develops due to genetic but also environmental factors, so much so that one 2020 study released by Lancet Commission has determined the 12 risk factors that can contribute to its development (hypertension, obesity, hearing problems, smokedepression, low physical activity, diabetes, lack of social contact, low level of education, excessive alcohol consumption, brain trauma And air pollution).

The Food and Drug Administration has approved the use of monthly Donanemab (350 mg/20 mL injection once monthly by intravenous infusion), the first and only therapy targeting amyloid plaques with evidence to support discontinuation of therapy when amyloid plaques are removed. This monoclonal antibody is intended for adults with early symptomatic Alzheimer’s diseaseincluding people with mild cognitive impairment, mild stage dementia, and confirmed amyloid pathology.

“Donanemab has demonstrated very significant results in people with early, symptomatic Alzheimer’s disease, where there is an urgent need for effective treatment options. We know that these medicines have the greatest potential benefit when people are treated early, and we are working closely with many stakeholders to improve the detection and diagnosis of this disease,” he said. Elias Khalil, President and CEO Lilly Italy hub. “We are deeply grateful to the patients and their loved ones who have participated in our clinical trials and to the scientists and collaborators at Lilly who have persevered in research for decades. Every year, more people are at risk of developing this disease, and we are determined to improve their lives.”

What is amyloid?

Amyloid is a protein naturally produced by the body that can clump together to create amyloid plaques. The excessive buildup of amyloid plaques in the brain can lead to memory and thinking problems associated with Alzheimer’s disease. Donanemab can help the body remove excess amyloid plaque buildup and slow the decline that can impair people’s ability to remember new information, important dates and appointments, plan and organize, prepare meals, use appliances, manage finances, and maintain independence.

What results emerged from the studies?

The results of the phase 3 TRAILBLAZER-ALZ 2 study were published on the Journal of the American Medical Association (JAMA) and showed that the People in a less advanced stage of the disease had the best results with donanemab. Study participants were evaluated for 18 months in two groups: a group of patients with a less advanced stage of the disease (those with low to medium levels of tau protein) and the overall population, which also included participants with high levels of tau. Treatment with donanemab significantly slowed clinical decline in both groups. Individuals treated with donanemab at a less advanced stage of the disease showed a significant slowing of cognitive decline (35 percent) compared to placebo on the Integrated Alzheimer’s Disease Assessment Scale (iADRS), which measures memory, thinking, and daily functioning. In the overall population, the response to treatment was also statistically significant, at 22 percent, using the iADRS. Between the two groups analyzed, those treated with donanemab had up to a 39 percent lower risk of progressing to the next clinical stage of the disease compared to those treated with placebo.

In the overall population of participants, donanemab reduced amyloid plaques by an average of 61 percent at 6 months, 80 percent at 12 months, and 84 percent at 18 months compared to baseline. One of the study’s goals was to remove amyloid plaques to minimal levels consistent with a visually negative scan using amyloid positron emission tomography (PET). If participants reached these levels, they stopped donanemab and were switched to placebo for the remainder of the study.

Potential side effects

Donanemab may cause amyloid-related imaging abnormalities (ARIA), which is a potential side effect of therapies targeting amyloid plaque. This event can be detected by magnetic resonance imaging (MRI) and, when it occurs, may present as temporary swelling in one or more areas of the brain, which usually resolves over time, or as small areas of bleeding within or on the surface of the brain. In rare cases, larger areas of cerebral hemorrhage may occur.
ARIA is usually asymptomatic, but can be serious and life-threatening events can occur. Donanemab may also cause certain types of allergic reactionssome of which can be serious and, in very rare cases, fatal, typically occurring during the infusion or within 30 minutes of the infusion. Headache is another side effect commonly reported.

The Research Continues

Lilly continues to study donanemab in several clinical trials, including TRAILBLAZER-ALZ 3, which focuses on preventing symptomatic Alzheimer’s disease in participants with preclinical AD; TRAILBLAZER-ALZ 5, a registrational study for early symptomatic AD currently enrolling in China and Korea; and TRAILBLAZER-ALZ 6, which focuses on improving our understanding of ARIA through novel MRI sequences, blood biomarkers, and different donanemab dosing regimens.