Lilly releases donanemab data that demonstrated relationship between reduction of amyloid plaque and slowing of cognitive decline
Donanemab is an investigational antibody that targets a modified form of beta amyloid plaque called N3pG. In
"We are excited by these promising results, which provide further evidence on the potential for donanemab to slow disease progression for people with early symptomatic Alzheimer's disease," said
In the first oral presentation, donanemab induced rapid amyloid plaque reduction at 24 weeks in participants with early symptomatic AD, with the most rapid clearance in subjects with the most severe plaque burden at baseline. The subset of participants who reached complete amyloid plaque clearance at 24 weeks (defined as an amyloid level of <24.1CL) were able to stop or reduce dosing of donanemab earlier than other patients. Among those who achieved complete amyloid plaque clearance at 24 weeks and had a blinded switch to placebo, an exposure-response model showed minimal amyloid re-accumulation over the next year.
Additionally, among those who reached early complete amyloid plaque clearance status at 24 weeks, a flortaucipir positron emission tomography (PET) scan at 76 weeks showed a significant decrease of tau spread – a predictive biomarker for AD progression – over 76 weeks in frontal, parietal and temporal brain regions compared to placebo.
Greater amyloid plaque change at 24 weeks was also associated with improved Integrated Alzheimer's Disease Rating Scale (iADRS) score, a validated, composite measure that combines two well-established instruments used to assess cognition and daily function in AD clinical trials. Additionally, pharmacokinetic/pharmacodynamic modeling showed that greater relative amyloid plaque clearance was correlated with greater clinical benefit.
A second oral presentation focused on plasma P-tau217 (tau phosphorylated at threonine 217), a research blood-biomarker developed by
"Notably, these data support the amyloid cascade hypothesis and suggest that amyloid-related tauopathy can be altered with donanemab's impact on plaque clearance. Furthermore, the data support that early and profound amyloid clearance may translate into clinical benefit for patients," said
Donanemab is an investigational antibody that targets a modified form of beta amyloid plaque called N3pG. Results from a Phase 2 study of donanemab were announced and published earlier this year, and in
In the TRAILBLAZER-ALZ study, donanemab dosing was 700 mg every four weeks for the first three doses, then 1400mg every four weeks, for up to 76 weeks. Planned blinded dose reduction evaluations occurred at 24 and 52 weeks.
Donanemab is also being studied in the ongoing Phase 3 TRAILBLAZER-ALZ 2 study in early, symptomatic Alzheimer's disease patients. TRAILBLAZER-ALZ 3, a prevention study, will evaluate whether treatment with donanemab can prevent the clinical progression of Alzheimer's disease in trial participants before clinical impairment begins. Visit LillyMemoryTrials.com for additional information on enrolling in Alzheimer's disease trials.
About Alzheimer's Disease
Alzheimer's disease is a fatal illness that causes progressive decline in memory and other aspects of cognition. Dementia due to Alzheimer's disease is the most common form of dementia, accounting for 60 to 80 percent of all cases.1 There are currently over 50 million people living with dementia around the world, with numbers expected to increase to nearly 152 million by 2050.2 Almost 10 million new cases of dementia are diagnosed each year worldwide, implying one new case every 3 seconds, and a significant increase in the caregiving burden placed on society and families. In the US alone, there was an increase of 8 million new caregivers from 2015 to 2020.3 The current annual societal and economic cost of dementia is estimated at
In an addition to age and family history of AD, the greatest risk factor for developing AD is the presence of the apolipoprotein E ε4 (APOE4) allele.1 Having one APOE4 allele increases the risk of developing Alzheimer's disease by approximately three times compared with those with two copies of the APOE3 form. Those who inherit two copies of the APOE4 allele have an 8 - 12-fold risk. In addition, those with the APOE4 allele are more likely to have beta-amyloid accumulation and Alzheimer's dementia at a younger age than those with the APOE2 or APOE3 forms of the APOE gene.
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about donanemab as a potential treatment for people with Alzheimer's disease and reflects
Alzheimer's Association. Facts and Figures. https://www.alz.org/alzheimers-dementia/facts-figures. Accessed December 8, 2020. Alzheimer's Disease International. World Alzheimer Report 2019. https://www.alz.co.uk/research/WorldAlzheimerReport2019.pdf. Accessed December 8, 2020. AARP. 2020 Report: Caregiving in the U.S.https://www.aarp.org/content/dam/aarp/ppi/2020/05/full-report-caregiving-in-the-united-states.doi.10.26419-2Fppi.00103.001.pdf. Accessed December 8, 2020.
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