CTAD 2022 – donanemab could be the plaque clearer king
While Lilly awaits results of donanemab’s pivotal Trailblazer-Alz 2 study next year, investors now have a positive signal. Trailblazer-Alz 4, a small trial pitting donanemab against Biogen’s Aduhelm, has suggested that the Lilly project could clear amyloid more quickly than any other amyloid-beta MAb. Lilly had already toplined Trailblazer-Alz 4 as positive, and this evening the CTAD conference saw full results in what was billed as the first active comparator data on plaque clearance in early symptomatic Alzheimer’s. In just six months donanemab-treated patients saw a mean 63% reduction in brain amyloid – a figure Aduhelm and Eisai’s lecanemab only reached a year later in separate, pivotal trials. The mean six-month reduction for Aduhelm in Trailblazer-Alz 4 was 16% – broadly in line with both the negative Engage study and the arguably positive Emerge trial. 37.9% of donanemab patients achieved six-month plaque clearance, versus 1.6% on Aduhelm, and Aria-E and symptomatic Aria-E rates were around 20% and 3% respectively, similar across the two cohorts. The big question is: so what? Until donanemab shows evidence of activity on disease in a controlled study the plaque data will do little beyond backing its mechanism of action.
|Plaque clearance by amyoid-beta MAbs across four studies|
|Mean brain amyloid levels*|
|Study||Project||Baseline||6mth||18mth||Difference at 6mth**|
|Emerge||Aduhelm (high dose)||85||66||25||-22%|
|Engage||Aduhelm (high dose)||91||76||37||-17%|
|Notes: *units are Centiloids, which express the Standard Uptake Value Ratio used to quantify the PET signal; in Clarity-AD Eisai set 30 Centiloids as the threshold above which subjects are considered to have elevated brain amyloid; in Trailblazer-Alz 4 plaque clearance was defined as ≤24.1 Centiloids; **difference not adjusted for the placebo cohorts used in Emerge, Engage & Clarity-AD. Source: Aduhelm label & CTAD.|
This story has been amended to correct the six-month value for Aduhelm in the Emerge trial.