Eli Lilly Alzheimer’s Drug Fails to Prevent Disease in Trial

An experimental Eli Lilly & Co. drug failed to prevent cognitive decline in people at risk for Alzheimer’s disease in a closely watched drug trial backed by the company and the US government.

(Bloomberg) — An experimental Eli Lilly & Co. drug failed to prevent cognitive decline in people at risk for Alzheimer’s disease in a closely watched drug trial backed by the company and the US government.

The drug, solanezumab, “did not slow the progression of cognitive decline” in a trial of more than 1,100 people, Eli Lilly said in a statement Wednesday. The participants were between 65 and 85 and were at risk of the devastating brain disorder because they had high levels of a toxic protein called amyloid in their brains.

While expectations for solanezumab were low because it failed in earlier trials, the results are a setback for Alzheimer’s researchers expecting an onslaught of new cases as the population ages. The latest trial was one of the biggest ever conducted to examine whether medications targeting amyloid can delay the onset of cognitive impairment.

“It is very disappointing,” John Sims, head of medical and global brand development for solanezumab at Eli Lilly, said in an interview. 

Amyloid Buildup

The failure could add to longstanding controversy over a major theory about the cause of Alzheimer’s — a disease that typically develops in old age and affects memory, thought and language. Many scientists have hypothesized Alzheimer’s is caused by a buildup of amyloid. 

Over the years, most trials of amyloid-lowering drugs have fallen short or produced mixed results in Alzheimer’s patients. Researchers have started testing drugs at earlier stages of the disease, with the idea that treating earlier is more likely to have an impact. 

Read More: Drugmakers Are Testing Ways to Stop Alzheimer’s Before It Starts

Solanezumab, which was designed to prevent amyloid buildup by clearing smaller fragments, was first used in three trials with patients who already had symptoms of Alzheimer’s. It didn’t clearly work. The most recent trial was designed to test — using a higher dose of the drug — whether solanezumab would prevent cognitive decline in people who were deemed at risk but weren’t yet showing symptoms.

It failed to do that and amyloid levels continued to rise in the study’s participants, Lilly said. Solanezumab was no better than placebo on all the primary and secondary outcomes examined.

In fact, at the end of the trial people who’d been on placebo tended to decline less on various cognitive tests compared to people who’d gotten solanezumab, although the differences weren’t statistically meaningful. The trial results will be presented at a scientific meeting later this year and also published in a scientific journal, according to Lilly.

“These data suggest that we may need to be more aggressive with amyloid removal even at this very early stage of disease,” said Reisa Sperling, a Harvard Medical School neurologist and project director for the trial. 

Lilly is studying another, more potent anti-amyloid drug called donanemab in a phase 3 treatment trial. Investors are closely focused on the drug and results of the trial are expected this year. The company also has started a prevention trial of donanemab.  

Eisai Co.’s Leqembi, which was approved in the US in January for Alzheimer’s disease, is also being tested in a large prevention trial. Last fall, it became the first anti-amyloid drug to unambiguously show that it slowed disease progression in a phase 3 trial.

Read More: Why Lecanemab Sparks Cautious Hope About Alzheimer’s

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