Lilly and Banner Alzheimer's Institute Launch Phase 3 Prevention Trial of Donanemab in Asymptomatic Individuals at Risk for Alzheimer’s Disease
Jul 16, 2021 05:17
CST Updated
05:17
Eli Lilly
Global Pharmaceutical R&D and Production Company
Banner Alzheimer's Institute
A Healthcare Service Provider
Alzheimer's disease-AD (Image source: tecake.in)
July 16, 2021 /BioonBIOON/ --Eli Lilly(Eli Lilly) and Banner Alzheimer's Institute (BAI) recently announced a strategic research collaboration to conduct a Phase 3 prevention trial (TRAILBLAZER-ALZ 3) of the anti-β-amyloid antibody donanemab. This is a randomized, double-blind, placebo-controlled study that will enroll trial participants at risk of experiencing cognitive and functional decline associated with Alzheimer's disease (AD), to evaluate whether donanemab treatment can delay the clinical progression of AD in trial participants.
Donanemab is a monoclonal antibody targeting N3pG (a modified form of β-amyloid).. Data from the Phase 2 TRAILBLAZER-ALZ study (NCT03367403), released in January this year, indicate that,In patients with early symptomatic Alzheimer's disease, donanemab treatment significantly slowed the decline in a composite measure of cognitive and daily function compared with placebo.Currently,Eli LillyAnother randomized, placebo-controlled, double-blind, multicenter Phase 3 study, TRAILBLAZER-ALZ 2 (NCT04437511), is also being conducted to evaluate donanemab in patients with early symptomatic AD.
Phase III of This Collaboration`Clinical trial`, willEvaluate whether donanemab can prevent the clinical progression of AD in patients with evidence of AD pathology but who have not yet manifested clinical symptoms.As part of the collaboration, BAI will leverage its expertise and established leadership in AD prevention trials, and through the Alzheimer's Prevention Registry (APR) GeneMatch program, support the enrollment of trial participants with and without the apolipoprotein E4 (APOE4) gene. This collaboration will introduce a more virtual approach to evaluating AD prevention therapies. Eli Lilly and BAI are committed to utilizing screening and treatment data as a shared scientific resource.Eli LillyremainsClinical Trialthe sole sponsor, and plans to begin participant enrollment for the trial later this year.
Mark Mintun, Vice President of Pain and Neurodegeneration at Eli Lilly, stated: “This collaboration combines Eli Lilly's more than 30 years of Alzheimer's disease research with BAI's unique expertise, demonstrating our shared commitment to identifying potential therapeutic approaches in healthcare to halt this devastating disease. Our TRAILBLAZER-ALZ 3 trial will evaluate whether donanemab can prevent the clinical progression of AD in patients with evidence of Alzheimer's pathology who have not yet exhibited clinical symptoms. While these types of trials are highly challenging in terms of both enrollment and conduct,`Eli Lilly`and BAI are honored to have the opportunity to conduct this new study in an area of high unmet medical need.”
Eric M. Reiman, one of the principal investigators for the TRAILBLAZER-ALZ 3 trial and Executive Director of the Banner Alzheimer's Institute (BAI), said: "We are pleased to have the opportunity toEli Lillycollaborate to identify an effective AD prevention therapy as soon as possible, introduce novel approaches to enhance the scale, speed, and accessibility of participation in AD prevention trials, and conduct them in a manner that may benefit the entire field. We must do everything in our power to discover and support the availability of effective preventive therapies for this devastating disease; this trial incorporates several potentially transformative elements to advance this effort.”
β-amyloid plaques in the brains of AD patients (Image source: hysiciansweekly.com)
TRAILBLAZER-ALZ was a randomized, placebo-controlled, double-blind, multicenter Phase 2 study designed to evaluate the safety, tolerability, and efficacy of donanemab in early symptomatic Alzheimer's disease (AD). The trial enrolled 272 patients selected based on cognitive assessment as well as amyloid plaque and tau imaging. The primary endpoint was the change from baseline to Week 76 in the integrated Alzheimer's Disease Rating Scale (iADRS) score. The iADRS is a comprehensive clinical instrument that combines a cognitive measure—the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13, cognitive function)—and a functional measure—the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living scale (ADCS-iADL, functional capacity). Key secondary endpoints included the changes from baseline to Week 76 in the scores of the ADAS-Cog13, ADCS-iADL, Mini-Mental State Examination (MMSE), and Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB). Other secondary`Biomarker`Endpoints include changes from baseline to Week 76 in brain amyloid deposition and brain tau deposition.
Results published in January this year showed that the study met its primary endpoint:From baseline to Week 76, the decline in iADRS score was slowed by 32% in the donanemab group compared with the placebo group.Compared with placebo, donanemab also demonstrated consistent improvements across all prespecified secondary endpoints measuring cognitive and functional abilities, but did not achieve nominal statistical significance on any individual secondary endpoint.
By targeting N3pGβ-amyloid, donanemab treatment has been shown to rapidly result in high levels of amyloid plaque clearance, as measured by amyloid imaging.In the TRAILBLAZER-ALZ study, at Week 76 of treatment, patients in the donanemab group demonstrated a reduction of 84 Centiloid units in amyloid plaque burden (measured on the Centiloid scale) from a baseline of 108 Centiloid units (a value below 25 Centiloid units is typically indicative of a negative amyloid scan). In this study, donanemab treatment was discontinued and patients were switched to placebo once their plaque levels fell below 25 Centiloid units on two consecutive assessments or below 11 Centiloid units on any single assessment.
In this study, the safety profile of donanemab was consistent with observations from Phase I study data, with amyloid-related imaging abnormalities (ARIA) observed, which is consistent with amyloid plaque-clearing antibodies. In the donanemab treatment group, 27% of subjects experienced amyloid-related imaging abnormalities-edema (ARIA-E), and 6% of subjects experienced symptomatic ARIA-E. (Bioon.com)