A trial of Eli Lilly’s Alzheimer’s disease drug solanezumab, which began in 2013, showed no benefit in patients, who were followed for a decade to try to determine whether the drug targeting the amyloid could slow down the disease.
Lilly’s study recruited around 1,100 patients between the ages of 65 and 85 who had not yet shown signs of clinical impairment but had brain scans showing buildup of amyloid plaque, an early diagnostic signal for the disease. of Alzheimer’s. Patients received the drug for four and a half years and were followed for the rest of the study – far longer than the year or two that is more common for such trials.
But even over a decade, solanezumab failed to slow patients’ cognitive decline or progression to symptomatic Alzheimer’s disease compared to a placebo, Lilly said in a press release.
John Sims“The study clearly showed that both primary and secondary endpoints were not met,” said John Sims, head of drug development at Lilly. “The A4 study concludes our clinical development of solanezumab and indicates that targeting soluble amyloid-beta by this mechanism is not effective in this population.”
In most cases, the failure is academic. Lilly reported major phase III trial failures of solanezumab in 2012 and 2016, during the height of the latest wave of interest in anti-amyloid drugs. Since then, a new generation of therapies, including Lilly’s donanemab and Biogen and Eisai’s newly approved Leqembi, have offered hope for the amyloid theory with the idea that removing plaque can slow the progression of disease when previous drugs did not.
“We believe these results were widely expected by investors,” said Jefferies analyst Michael Yee.
Amyloid hypothesis
Lilly’s drug targeted the soluble form of amyloid but had no effect on clearing already accumulated plaques in the brain. While the exact cause of Alzheimer’s disease still remains unknown, the latest theories are that the newer, more powerful drugs may have an impact where earlier drugs had none.
The results “actually provide further evidence that Abeta therapies targeting insoluble Abeta will be more effective in slowing cognitive decline,” Yee said, using shorthand for amyloid-beta protein. “It’s about having enough plaque to start with and targeting the right form of Abeta to get a clinical response,” Yee said in his memo.
Shares of Biogen rose about 1.6% in post-trade trading on Wednesday, while Eisai was little changed in Japan. Lilly shares were little changed in early trading Thursday.
Lilly used the announcement to tout its next-generation therapies for Alzheimer’s disease, donanemab and remternetug. Both drugs are in Phase III trials, with initial data on donanemab expected in the coming months in the TRAILBLAZER-ALZ 2 study. Remternetug readout may come later, with primary completion expected for early 2024, according to clinictrials.gov.
The company pointed out that donanemab and remternetug “are different from solanezumab in that they specifically target deposited amyloid plaque and have been shown to result in plaque clearance in treated patients.”