A trial of Eli Lilly’s Alzheimer’s drug solenzumab that began in 2013 showed no benefit in patients who were followed for a decade and answered whether the amyloid-targeting drug could slow the disease.
Lilly’s study enrolled nearly 1,100 patients aged 65 to 85 who had not yet shown signs of clinical impairment, but whose brain imaging scans showed amyloid plaque accumulation, which is suggestive of Alzheimer’s. The initial diagnosis was indicative. Patients received the drug for four and a half years and were followed for the rest of the study — a year or two more than is typical for these types of trials.
But for more than a decade, solenzumab failed to slow patients’ cognitive decline or the progression of symptomatic Alzheimer’s disease compared to a placebo, Lilly said in a press release.
“The study clearly showed that the primary and secondary endpoints were not met,” said John Sims, Lilly’s head of drug development. “The A4 study concludes our clinical development of solenzumab and indicates that targeting soluble amyloid beta through this mechanism is not effective in this population.”
In most ways, failure is academic. Lilly reported the failure of phase III trials of solenzumab in 2012 and 2016, when the last wave of interest in amyloid-clearing drugs peaked. Since then, a new generation of therapies, including Lilly’s donanumab and Biogen and Christian’s newly approved Lekembi, have offered hope to the amyloid theory, along with the idea that clearing plaques might slow disease progression when first detected. There were no medicines.
“We think these results were largely expected by investors,” said Michael Yee, an analyst at Jefferies.
Lilly’s drug targeted the soluble form of amyloid but had no effect on clearing plaques that had already accumulated in the brain. While the exact cause of Alzheimer’s is still unknown, the latest theories are that newer, more potent drugs may have an effect while earlier drugs did not.
The results “really provide further evidence that Abeta therapy targeting insoluble Abeta is going to be better at slowing cognitive decline,” Yee said, using a shorthand for amyloid beta protein. “It’s all about having enough plaque to initiate and target the right form of Abeta to get a clinical response,” Yee said in his note.
Shares of Biogen were up about 1.6% in after-market trading on Wednesday, while Japan’s Eisai was little changed. Shares of Lilly were little changed in early trading Thursday.
Lilly used the announcement to tout its next generation of Alzheimer’s treatments, donnemab and remtrenetag. Both drugs are in Phase III trials, with topline data for donemab expected in the next few months from the Trailblazer-ALZ2 study. The readout for Remterneg could come later, according to ClinicalTrials.gov, with a primary completion in early 2024.
The company stressed that donnumab and remternetag “differ from solenzumab in that they specifically target deposited amyloid plaque and have been shown to lead to plaque clearance in treated patients.”