Thirty-five percent. That is how much Eli Lilly said its experimental Alzheimer’s drug donanemab slowed clinical and functional decline in a late-stage trial, and Daniel Skovronsky, Lilly’s top science executive, called it the first Phase III result for any investigational Alzheimer’s medicine to reach that mark. The figure puts Lilly squarely in the path of Eisai and Biogen, whose rival antibody Leqembi (lecanemab) had won accelerated FDA approval that January.
The bottom line for the sector: the market has finally got a real contest.
By the numbers
The trial, TRAILBLAZER-ALZ 2, was randomized, double-blind and placebo-controlled. It enrolled people with early symptomatic Alzheimer’s, meaning mild cognitive impairment or the mild dementia stage, with confirmed Alzheimer’s pathology in the brain. Patients stopped taking donanemab once their amyloid plaque had cleared to a set level. Lilly said the drug hit its primary goal, a change from baseline at 18 months on the iADRS, a scale covering thinking and daily tasks like handling money, along with every secondary endpoint.
Leqembi’s own Phase III trial, CLARITY-AD, cut clinical decline by 27% against placebo after 18 months as measured on the CDR-SB scale. Lilly’s donanemab slowed decline by 37% in patients with intermediate tau levels, the group the trial mainly targeted. Across the whole study population the figure was 29%, two percentage points ahead of Leqembi.
Neither company is claiming a win. “There are no head-to-head clinical trials comparing Leqembi (lecanemab-irmb) to donanemab so we cannot make comparisons,” an Eisai spokesperson told BioSpace. Dawn Brooks, Lilly’s global development leader for donanemab, agreed that direct comparison could mislead, since the patients and the way they were evaluated differed.
The safety column
Investors will note that efficacy looks close while safety does not. In TRAILBLAZER-ALZ 2, two deaths were conclusively linked to amyloid-related imaging abnormalities, known as ARIA, and a third followed a serious ARIA episode without being explicitly attributed to it. Brain microhemorrhages showed up in 31.4% of donanemab patients and temporary swelling in 24%. CLARITY-AD recorded 17% and 12.5% for the same two events. Mizuho Securities told clients that efficacy seemed more comparable, while “safety looks better with Biogen’s Leqembi.”
Brooks said ARIA is a risk that must be monitored with every amyloid-targeting therapy.
How the market reacted
Lilly’s stock climbed nearly 7% by the close that Wednesday. Prothena, which has two early-stage Alzheimer’s candidates, gained 28%, and Annovis Bio rose 6%. Biogen and Eisai barely moved, up .56% and .49%.
The prize is large. An estimated 6.7 million Americans live with Alzheimer’s, more than 3,000 clinical trials are under way, and one outlet put the market at $6B within a couple of years. Lilly said it would file with the FDA that quarter, and it was still running TRAILBLAZER-ALZ 3, a study in people with preclinical disease aimed at preventing symptoms.
Sources
- Lilly's Donanemab Data Energizes Alzheimer's Sector, Safety Concerns Remain – BioSpace
- Lilly's Donanemab Shines in Phase III for Alzheimer's – Inside Precision Medicine
