Brain MRI Scan of Healthy Male  ( Magnetic Resonance Imaging) High Resolution
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After decades of disappointment, drugmakers are finally making progress with disease-modifying drugs for Alzheimer’s disease. Eli Lilly announced today that its investigational drug donanemab ,an investigational amyloid plaque targeting therapy, significantly slowed cognitive and functional decline in people with early symptomatic Alzheimer’s in a late-stage trial.

This puts Lilly in a position to catch up with the team of Biogen and Eisai whose Leqembi (leconemab-irmb) was approved for Alzheimer’s in January of this year. In Sept. 2022 they announced that an almost 1,800-patient Phase III trial found Leqembi slowed the progression of Alzheimer’s disease by 27% over 18 months compared with a placebo.

Lilly seems to have bested that, by quite a bit.

“This is the first Phase III trial of any investigational medicine for Alzheimer’s disease to deliver 35% slowing of clinical and functional decline,” said Daniel Skovronsky, MD, PhD, Lilly’s chief scientific and medical officer, and president of Lilly Research Laboratories.

Lilly says it will proceed with global regulatory submissions as quickly as possible and anticipates making a submission to the FDA this quarter.

The biological cause of Alzheimer’s has been hotly debated for a long time. There have also been discussions about how these trials are carried out. But Alzheimer’s is a huge unmet need. An estimated  6.7 million Americans alone suffer from this disease. Over 3,000 clinical trials are ongoing in this condition, whose market is expected to beaver $6B in within the next couple of years.

Lilly has offered up a lot of data about their drug. TRAILBLAZER-ALZ 2, a randomized, double-blind, placebo-controlled study, evaluated the safety and efficacy of donanemab.

The study enrolled people with early symptomatic Alzheimer’s disease , which includes mild cognitive impairment (MCI) and the mild dementia stage of disease, with the confirmed presence of AD neuropathology, and participants completed their course of treatment with donanemab once they reached a prespecified level of amyloid plaque clearance.

Donanemab met the primary endpoint of change from baseline until 18 months on the integrated Alzheimer’s Disease Rating Scale (iADRS). The primary endpoint of iADRS measures cognition and activities of daily living such as managing finances, driving, engaging in hobbies, and conversing about current events. All secondary endpoints of cognitive and functional decline were also met and showed highly statistically significant clinical benefits with similar magnitude.

“Over the last 20 years, Lilly scientists have blazed new trails in the fight against Alzheimer’s disease by elucidating basic mechanisms of AD pathology and discovering imaging and blood biomarker tools to track the pathology,” said  Skovronsky. “We are extremely pleased that donanemab yielded positive clinical results with compelling statistical significance for people with Alzheimer’s disease in this trial.

Lilly previously announced and published in the New England Journal of Medicine results from the Phase II TRAILBLAZER-ALZ study in 2021. In addition, Lilly shared data from TRAILBLAZER-ALZ 4, the first active comparator study in early symptomatic Alzheimer’s disease, at the 15th Clinical Trials on Alzheimer’s Disease conference in 2022.

Lilly continues to study donanemab in multiple clinical trials, including TRAILBLAZER-ALZ 3, which is focused on preventing symptomatic Alzheimer’s disease in participants with preclinical AD.

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