New data on Eli Lilly's experimental Alzheimer's drug backs a hotly debated scientific theory, but shows mixed benefits for patients

• Eli Lilly's experimental treatment slowed down cognitive decline by 32% in a midstage trial.
• But the drug missed most of the secondary trial goals, including one watched by experts.
• An Eli Lilly executive told Insider the data was mixed, but very exciting.

The latest test of Eli Lilly's Alzheimer's disease drug ended with a mixed bag of results that disappointed investors.

Lilly gave an in-depth look at the performance of its drug, called donanemab, on Saturday at the International Conference on Alzheimer's and Parkinson's Diseases. The drug met the trial's primary goals, reducing a harmful substance that builds up in the brains of patients with Alzheimer's disease. It also slowed down the rate of cognitive decline by 32%, according to data published Saturday in a medical journal. But it missed the mark on several secondary tests.

The Alzheimer's drug-development field has been marked by failure after failure, so the news that Lilly may have a working drug sent a surge of energy through the field when the drugmaker first disclosed some information about the results in January.

Those earlier failures - even within Lilly's own drug-development pipeline - may have skewed the expectations for donanemab. Dr. Mark Mintun, the vice president of the Alzheimer's disease unit at Lilly, said he couldn't think of a similar Alzheimer's disease trial that hit its primary goal.

So, investors were chomping at the bit to see the full donanemab data. But the data didn't meet expectations.

Half of the 60 investors that analysts at financial firm Mizuho polled felt the trial results were worse than they had anticipated. Lilly's stock tumbled 8% when markets opened Monday.

The donanemab data may give hope to the scientific community and other drug companies, but analysts and Alzheimer's disease experts said the jury is still out on how effective the drug will be for patients themselves.

Donanemab missed the mark on a memory assessment experts were watching

Donanemab was designed to target a plaque that builds up in the brains of Alzheimer's patients called amyloid beta. The hope is that getting rid of the plaque will reduce the rate of decline of a person's memory and cognition.

Scans of trial participants' brains showed that people taking donanemab did see their plaques fade away. That's not only a boon to Eli Lilly, but other drugmakers that are working on treatments targeting amyloid beta, such as Biogen and Roche.

It wasn't as clear how much benefit donanemab had on subjects' ability to recall words, follow instructions and other abilities lost to dementia.

The drug passed the main test of memory and cognition.

But Alzheimer's experts had their eyes on one datapoint in particular: the scores from a widely accepted dementia assessment known as CDR-SB. The tool is used to measure things like memory and judgement, as well as a person's ability to do household chores and maintain their personal hygiene. The higher the score, the more skills have been lost to dementia like Alzheimer's.

Eli Lilly's drug didn't meet expectations there.

The company reported that trial participants taking donanemab had a 0.36 point score difference compared to the participants that received a placebo treatment.

For comparison, Dr. Lon Schneider, director of the California Alzheimer's Disease Center at University of Southern California, had hoped to see at least a one-point difference, according to the Wall Street research firm Mizuho.

Mintun, the Eli Lilly executive, said he hadn't expected that donanemab would pass all five dementia tests, calling it statistically impossible. But giving patients more time to hold onto memories is meaningful for them, he said.

The clinical trial took a 'Goldilocks approach,' and more testing is needed

The donanemab trial assessed a small and very specific group of patients. The trial was limited to participants with amyloid plaques, as well as another protein linked to Alzheimer's called tau. Dr. Howard Fillit, executive director of the Alzheimer's Drug Discovery Foundation, called it a Goldilocks approach - in the end, Lilly ended up with participants whose Alzheimer's disease wasn't too early or too advanced.

The narrow parameters for patient enrollment came with positives and negatives, former Lilly executive and current Karuna Therapeutics CEO Steven Paul said.

It may have enabled Lilly to avoid other Alzheimer's trial pitfalls, but the enrollment criterea also raised many questions about who donanemab would be useful for. Would the drug work for asymptomatic patients? Is the trial data just showing a temporary delay in memory erosion?

Fillit, Alzheimer's disease researcher Rudy Tanzi and several analysts said that Lilly will need to run another clinical trial, preferably a much larger late-stage test with participants from multiple countries, if it wants to bring the treatment to the US Food and Drug Administration for approval. In particular, the company would need to show the drug works, as measured by the CDR-SB score, Tanzi said.

Eli Lilly's current plan is to run at least one more mid-stage trial. The format of that trial had already been set, but Mintun said the drug giant is discussing possible changes with the FDA, including potentially removing a significant CDR-SB change as the main goal.

Changing that CDR-SB requirement, particularly given that the original Phase 2 trial failed on that regard, would make investors skeptical of the drug, according to a note from Morgan Stanley analysts before the full results were announced.

Analysts at Leerink aren't confident that the new Phase 2 trial will be successful, no matter what the main end goal is, given that Lilly executives were mum on why donanemab missed most of the trial endpoints, including the CDR-SB test.

This article was updated on March 15 with analysts' notes and Lilly's stock move.