Eli Lilly’s amyloid-targeting antibody donanemab has shown promise in the treatment of Alzheimer’s disease, sending its stocks soaring and renewing hope for the notoriously complex research area.
In the ‘amyloid theory’, high levels of amyloid plaques are believed to be associated with Alzheimer’s disease and there is speculation that early intervention to prevent its development could benefit people with Alzheimer’s.
However, this theory has been tried and tried again, with a string of failures in the field that includes Lilly’s previous Alzheimer’s candidate solanezumab.
Patients treated with solanezumab in a phase 3 trial showed no significant evidence of a slowing in cognitive decline compared to those on placebo, and Lilly’s chief executive John Lechleiter confirmed in 2016 that the company would not be seeking approval of the drug for mild Alzheimer’s disease.
Donanemab, Lilly maintains, is different – it targets a modified form of beta amyloid called N3pG, a mechanism of action which has now yielded positive phase 2a results, according to the company.
Results from this trial – TRAILBLAZER-ALZ – showed that patients with early symptomatic Alzheimer’s treated with donanemab experienced a ‘significant slowing of decline in a composite measure of cognition and daily function’.
In other measures, however, including all secondary endpoints measuring cognition and function compared to placebo, donanemab did not reach statistical significance.
There were still ‘consistent improvements’ for patients treated with Lilly’s antibody across these measures, but without the detailed results the extent of this benefit remains unknown.
“This unique mechanism and antibody for clearing plaques, discovered at Lilly, has the potential to provide high levels of durable amyloid plaque clearance after limited duration dosing,” said Daniel Skovronsky, chief scientific officer and president of Lilly Research Laboratories.
“In conjunction with our expertise in amyloid and tau imaging, this allowed us to conduct a trial to test if reducing amyloid plaques in Alzheimer’s patients to levels seen in scans of healthy individuals could result in clinically meaningful slowing of cognitive decline,” he added.
Another amyloid-targeting treatment, Biogen’s aducanumab, is currently being reviewed by the US Food and Drug Administration (FDA).
In November 2020, however, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee overwhelmingly voted no on a number of counts regarding the efficacy and evidence supporting the use of this drug in Alzheimer’s.
Although the FDA is not required to follow guidance from expert panel decisions, it usually does so.
However, due to the lack of new treatments for Alzheimer’s emerging in the last decade, it may still approve aducanumab – the agency is set to announce its final decision on whether to approve the drug’s Biologics License Application (BLA) by 7 March 2021.