Older Eli Lilly's drug fails Alzheimer's prevention trial

By Deena Beasley

(Reuters) - An early-generation Alzheimer's drug from Eli Lilly and Co failed to slow cognitive decline in patients treated before they showed symptoms, but the large trial found a strong link between levels of brain plaques and disease progression, the company said on Wednesday.

The experimental drug, solanezumab, was designed to target only soluble forms of amyloid beta, a toxic protein that accumulates in the brains of people with Alzheimer's. The drug, which does not clear existing plaques, was abandoned by Lilly in 2016 after it did not slow loss of mental functioning in patients with mild Alzheimer's symptoms in clinical trials.

The latest data highlight the need for "more aggressive therapies to lower plaque," and will inform the structure of future trials of amyloid-targeting drugs, said John Sims, senior medical director at Lilly.

The U.S. drugmaker is in late-stage development with two other Alzheimer's drugs, donanemab and remternetug, that specifically target deposited amyloid and have been shown to clear plaque in treated patients.

Although Lilly halted development of solanezumab, it supported, along with the National Institute on Aging and others, the randomized clinical trial of the drug in over 1,100 asymptomatic Alzheimer's patients.

The study, which started in 2013, did not meet its primary goal of slowing cognitive decline, and placebo patients actually did better on secondary goals, such as changes in daily activity. Just over 36% of trial participants developed symptomatic Alzheimer's, and rates of progression were similar for both the treatment and placebo groups, Lilly said.

"Even at this preclinical stage of Alzheimer's disease, we are going to have to be more aggressive with amyloid." said Dr. Reisa Sperling, a neurologist at Harvard-affiliated Brigham and Women’s Hospital, who led the study. "We need to get people's amyloid lower, very fast, and keep it there."

Lilly expects to announce results from a Phase III trial of donanemab for early Alzheimer's before the end of June. If the findings are robust, the company will file for U.S. approval, which could occur in late 2023, Sims said.

The company is conducting a 3,300-patient trial of donanemab in asymptomatic Alzheimer's patients. It is also launching a late-stage trial of remternetug, which can be given by subcutaneous injection.

"We hope that if we can intervene on the amyloid and get rid of the plaque very early that we will have a fairly large effect on preventing people from becoming symptomatic," Sims said.

(Additional reporting by Julie Steenhuysen in Chicago; Editing by Bill Berkrot)