dm+d

Unassigned

New Medicines

Early Alzheimer's disease (MCI and mild)

Information

New molecular entity
Eli Lilly
Eli Lilly

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Pre-registration (Filed)
Aug 22Eli Lilly announce that donanemab has been accepted for priority review by FDA under the accelerated review pathway [21].
Feb 22Feb 22: Lily report the timeline for completing an accelerated approval request has been delayed due to limited coverage of Aduhelm to only patients participating in approved clinical trials. An FDA decision could arrive late this year or Q1 23, if the treatment is granted priority review [20].
Jan 22Donanemab is considered by analysts to have blockbuster potential [19].
Nov 21Has breakthrough therapy status in US [16].
Oct 21Filed in US under an accelerated approval pathway [14].
Sep 21Trailblazer-ALZ 2 has closed to new patients. Readout of results is anticipated around the first half of 2023. Lily is preparing for an accelerated approval to arrive in 2022, with a full approval in 2023 if the efficacy data is strong [13].
Aug 21Eli Lily reaffirm plan to submit drug to the FDA by end of year and announce enrollment has completed for the Trailblazer-ALZ clinical trial. Results from this PIII study will be used to support the filing [12].
Jun 21Lilly plans to file for accelerated approval later this year, based on the strength of PII data [11].
Jun 21Following full FDA accelerated approval for Aduhelm based on a surrogate endpoint, the path for donanemab appears clearer. Lily plan to re-engage with the FDA to better understand the bar donanemab needs to clear to potentially obtain a more expedited regulatory approval [10].
Jan 21Lilly suggests TRAILBLAZER-ALZ-2 study could serve as a confirmatory pivotal study and potentially support regulatory filings – dramatically shortening the development timeline for the drug [7].
Jan 21Company pipeline indicates in PII trials. [6]

Category

Humanised IgG1 monoclonal antibody - targets N3pG beta amyloid, resulting in amyloid plaque clearance [1,2]. Likely given 4-weekly.
Alzheimers disease is the most common form of dementia. It is estimated to affect 520 000 people in the UK. [3]
Early Alzheimer's disease (MCI and mild)
Intravenous

Trial or other data

Nov 21PIII TRAILBLAZER-ALZ 4 study to compare donanemab to aducanumab on amyloid plaque clearance in participants with early symptomatic AD starts (NCT05108922). 200 adults aged 50 to 85 years with a MMSE score between 20 and 30 will be recruited in the US. Patients will receive donanemab intravenously (IV) every 4 weeks or aducanumab (as per label). Primary outcome is percentage of participants who reach complete amyloid plaque clearance on Florbetapir F18 PET scan on donanemab vs. aducanumab at 6 months; collection of these data is due to complete Jun 22 [17].
Oct 21TRAILBLAZER-ALZ 2 study is also recruiting in the UK, Europe, Canada, Japan and Australia, in addition to the US [15].
Oct 21In March 21, Lilly expanded planned enrollment for the TRAILBLAZER-ALZ 2 study from 500 to 1,500, and re-classified it as a PIII study. Primary outcome will now be change from Baseline on the iADRS in participants with early symptomatic AD with demonstrated presence of low-medium tau pathology. Changes have been made to the secondary outcomes also. Collection of primary outcome data is due to complete Feb 23 [15].
Oct 21PIII follow-on TRAILBLAZER-EXT study is recruiting patients enrolled in previous sponsor-approved donanemab trials (NCT04640077). The main goals of this study are to further determine whether the study drug donanemab is safe and effective in participants with Alzheimer´s disease and to validate video scale assessments. In Part A, there will be alternating at-home and on-site cognitive and functional scale assessments, Group 1 having cognitive/functional scale assessment at the study site (on-site), followed by an at-home assessment (VTC; video teleconference), or Group 2 having cognitive/functional scale assessment at home (VTC), followed by assessment on-site. In Part B, donanemab will be administered intravenously (IV). 100 adults will be recruited in the US and Canada. Primary outcome data collection is due to complete May 23 [15].
Oct 21Lily plan PIII trial TRAILBLAZER-ALZ-4 head-to-head trial comparing donanemab to aducanumab to assess superiority of brain amyloid plaque clearance in early symptomatic Alzheimer´s disease. Primary endpoint results should be available H2 22 [14].
Mar 21Results of PII (TRAILBLAZER-ALZ ; NCT03367403) trial, published in NEJM [9].
Mar 21Eli Lilly announced that PII trial (TRAILBLAZER-ALZ; n=257) met its primary endpoint. Patients on donanemab experienced a 6.86 decline in scores on the Integrated Alzheimer´s Disease Rating Scale (iADRS) vs. 10.6 in the placebo group (lower scores indicate greater cognitive and functional impairment), p=0.04. However, concerns have been raised about the clinical significance of an improvement in iADRS given that the more commonly used Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) endpoint, was non-significant. Data is awaited from a further PII trial (TRAILBLAZER-ALZ 2; n=500) which uses change in CDR-SB as a primary outcome [8].
Jan 21 The safety, tolerability and efficacy of donanemab are also being evaluated in the ongoing placebo-controlled, double-blind, multi-center PII RCT TRAILBLAZER-ALZ 2 (NCT04437511). This study is still recruiting and has an estimated primary completion date of March 2023. [1,5]
Jan 21In TRAILBLAZER-ALZ (NCT03367403), a randomised, placebo-controlled PII RCT (N=272), the primary endpoint of change from baseline until 76 weeks in the Integrated Alzheimer´s Disease Rating Scale (iADRS) was met. Donanemab-treated pts showed an 84 centiloid reduction of amyloid plaque at 76 weeks vs. a baseline of 108 centiloids (< 25 centiloids is typical of a negative amyloid scan). Pts stopped receiving donanemab and switched to placebo onceplaque levels were < 25 centiloids for two consecutive measures or < 11 centiloids at any one measure. Key secondary endpoints include changes between baseline and 76 weeks in the ADAS-Cog13, ADCS-iADL, MMSE, and CDR-SB scores. Donanemab also showed consistent improvements in all prespecified secondary endpoints measuring cognition and function vs. placebo, but did not reach statistical significance on every secondary endpoint. With donanemab, amyloid-related imaging abnormalities – edema (ARIA-E) occurred in 27% of treated pts, with an overall incidence of 6% experiencing symptomatic ARIA-E. [1,4]

Pre-clinical Alzheimer's disease

Information

Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

None
None
Phase III Clinical Trials

Category

Humanised IgG1 monoclonal antibody - targets N3pG beta amyloid, resulting in amyloid plaque clearance
Alzheimers disease is the most common form of dementia. It is estimated to affect 520 000 people in the UK [1].
Pre-clinical Alzheimer's disease
Intravenous