Eli Lilly and Co said its experimental Alzheimer’s treatment failed to slow the loss of mental functioning in patients with mild symptoms, a major setback for the company and millions of people at risk of developing the memory-robbing disease.
Many investors and families had been counting on solanezumab to become the first approved medicine to slow progression of the disease, which the Alzheimer’s Association estimates will strike as many as 28 million Americans by mid-century.
Lilly shares were down 11.7% on Wednesday after the US drugmaker announced the long-awaited results of its large Expedition 3 study, which showed patients treated with solanezumab did not experience a significantly greater slowing in cognitive decline than those given placebos.
The news also caused a 4.3% drop in shares of Biogen Inc, which is testing a drug that, like solanezumab, targets the beta amyloid protein believed to cause toxic brain plaques that are considered a hallmark of Alzheimer’s.
Given the trial’s results, Lilly said it would not seek US approval of its drug for mild dementia.
Incoming Chief Executive Officer David Ricks called the news “heart-breaking”.
Lilly spent more than $3 billion on Alzheimer’s research over the past 27 years and will keep pushing for effective treatments, he said. He noted solanezumab was being studied in a separate trial called “A4” among people with no Alzheimer’s symptoms but who have the brain plaques.
The company said it would take a $150 million charge in the fourth quarter for the failed trial and provide an updated 2016 financial outlook, as well as 2017 forecasts, on December 15.
Ricks affirmed Lilly’s forecast for annual revenue growth of at least 5% between 2015 and 2020. The company has strong growth prospects without solanezumab because of recently approved treatments for diabetes, cancer and other conditions, he said.
Some analysts had said solanezumab, if approved, could generate up to $10 billion in annual sales and boost Lilly’s earnings for years to come.
The infused drug works by binding in the bloodstream to beta amyloid.
Biogen is racing to complete Phase III trials of aducanumab, which is designed to clear beta amyloid that has already formed plaques. However, the solanezumab data raises questions about whether beta amyloid is a valid target for Alzheimer’s drugs.
Biogen officials did not respond to requests for comment.
Still hope for treatments
As with cancer, many experts believe combinations of medicines, each having different mechanisms, will be needed to greatly slow Alzheimer’s progress or stop it in its tracks.
One of the biggest hopes is a class of experimental drugs called BACE inhibitors, which work by blocking production of beta amyloid. Lilly and others, including Biogen and Merck & Co, are conducting late-stage trials of such drugs.
Dr. Sam Gandy, director of Mount Sinai School of Medicine’s Center for Cognitive Health, was not ready to abandon drugs that reduce amyloid.
“My guess is that they would be part of a cocktail with something else, that they won’t in and of themselves be enough,” he said.
Amyloid drugs may work best in patients who have yet to develop plaques readable on scans, Gandy added.
In two original 18-month studies completed in 2012, solanezumab failed to slow cognitive decline or loss of physical functioning for the 1,000 patients with mild to moderate disease in each trial.
But the combined data for just mildly affected patients suggested solanezumab caused significant slowdowns of 34% in mental decline and 18% in loss of functional abilities, compared with those taking a placebo, researchers said.
For Expedition 3, Lilly extended the pair of large trials by another two years and enrolled only mildly impaired patients. Researchers continued to provide solanezumab to patients who had taken it during the initial studies and also allowed the placebo groups to switch to solanezumab.