While investors supported the sliver of promise offered when Eli Lilly and Co. said its Alzheimer’s drug may slow progression early in the disease, doctors weren’t as impressed, saying it could take years to find out for sure.
Lilly announced last week that its experimental treatment solanezumab failed to improve thinking skills, memory and function in a broad range of patients. At the same time, an unusual reanalysis of the data found the drug may slow mental decline in those with the mildest form of Alzheimer’s.
Investors responded on Aug. 24 by boosting Indianapolis-based Lilly's stock 3.4 percent. Current patients, though, found little solace in the result, said Samuel Gandy, director of Mount Sinai Center for Cognitive Health in New York.
The need to reanalyze the data “was a red flag,” Gandy said. “For the layman, this means poking around a dataset in hand, hunting for a result that may be statistically significant but is unlikely to be clinically significant. So caveat emptor here.”
About 5.4 million Americans have Alzheimer’s, the most- common form of dementia, and the number is expected to surge to as many as 16 million by 2050 as the population ages, according to the Alzheimer’s Association. Drugs on the market now address only the symptoms, not the underlying cause, and none has been shown to slow progression of the disease.
That makes the finding on solanezumab particularly crucial, doctors said, if it can be duplicated by further research.
Solanezumab limits growth of a protein called beta amyloid before it builds up in the brains of patients, forming clumps that many doctors believe to be the cause of Alzheimer’s. Whether this change makes a difference is a question still largely unanswered, said David Knopman, a neurologist at the Mayo Clinic in Rochester, Minn., and head of the data safety monitoring board for the solanezumab trials.
To find out for sure, Lilly probably will have to set up new research focusing only on mildly impaired patients.
“I take care of people with Alzheimer’s disease who desperately want to see something positive here,” Knopman said. “For my patients right now, absolutely it won’t be available commercially. I don’t want them thinking this is something being withheld by a ‘nasty’ Food and Drug Administration, or that the scientists are being too cautious. This was a negative study.”
Added trials could run as long as three years and cost several million dollars, said R. Scott Turner, director of the Memory Disorders Program at Georgetown University in Washington.
“On the first pass it’s a big disappointment that this was negative,” he said. ‘But there were hints of effectiveness and it was relatively safe. I don’t think it’s worth completely abandoning. I hope they would continue to invest in the drug and do the next trial.”
Company officials declined to say whether they are planning a new study focusing on patients with the mildest form of Alzheimer’s.
Lilly will present the current results, including the reanalyzed portion, to regulators worldwide and discuss what steps should be taken next, said Dave Ricks, the company’s senior vice president, in a conference call. He wouldn’t rule out anything, including filing for regulatory approval with the current results. The results also will be presented at two medical meetings in October, Lilly officials said.
When asked about additional solanezumab trials, his response was to point out that Lilly has other Alzheimer’s disease drugs in development, along with 11 unrelated medicines that are in the last of three stages of testing usually required for U.S. Food and Drug Administration approval.
J. Anthony Ware, group vice president of Lilly Bio-Medicines Product Development, said in a conference call that company officials were excited rather than surprised by the “glimmer of hope” seen in the secondary analysis.
The studies that failed to meet their goals initially are continuing, he said, with all patients now receiving the drug. That effort may yield additional information about the drug by 2014, Tim Anderson, an analyst with Sanford C. Bernstein & Co. in New York, wrote in an Aug. 22 note to investors.
“At this point, theoretically all possibilities are still on the table,” including Lilly seeking approval for its drug without added testing, he said.
The argument for such a move, would be “the large unmet medical need in patients with Alzheimer’s disease and the generally acceptable safety profile,” Anderson wrote.
The studies, dubbed Expedition 1 and Expedition 2, included about 2,000 patients, roughly two-thirds with mild disease and one-third with moderate disease.
The results of Expedition 1 came in first, with the medicine failing to slow mental and functional decline across all 1,000 patients. A planned analysis of just patients with mild disease showed those getting solanezumab were significantly less likely to worsen, the company said in its statement. After getting those results, Lilly altered the statistical plan for Expedition 2, which was still under way, to look only at cognition in those with mild disease.
The second trial didn’t show a significant benefit in patients with mild disease. When the results of the two studies were added together, giving more statistical power, there was a significant decline in the progression of the disease for mild patients alone and a combination of mild and moderate patients, the company said. The only group that didn’t benefit was patients with moderate disease.
While the Lilly findings probably won’t help current patients, success in patients with a mild form of the disease suggests that early testing for Alzheimer’s could one day make a big difference, said Ronald Petersen, a neurologist at the Mayo Clinic in Rochester, Minn.
“It does raise the million dollar question of are we still trying to treat these patients too late in the disease process,” said Petersen, who wasn’t involved in the studies and has no financial connection to Lilly. “It’s a mild clinical effect. At this stage of the disease, maybe that’s all we can expect.”