WASHINGTON, D.C. (TheStreet) -- Remember the dress that took over the Internet last winter? To some people, the dress was most definitely blue and black, others insisted the dress was white and gold. People saw different colors in the dress based on their perceptions of the image and how their brains processed that information.
Eli Lilly's (LLY - Get Report) solanezumab is the Alzheimer's drug equivalent of the Internet dress. New data disclosed Wednesday has some people seeing hope that solanezumab, if used early enough, can slow the declines in cognition, memory and function that are the terrible hallmarks of Alzheimer's.
Others looking at the same solanezumab data see not much of anything. The drug appears to be safe, but it's not benefiting Alzheimer's patients in a meaningful way.
The new, contentious solanezumab data come from from Lilly's EXPEDITION-EXT study, to be presented Wednesday afternoon at the Alzheimer's Association International Conference in Washington, D.C. Lilly announced the sola data in a press announcement ahead of the presentation. The full study results were also published in the medical journal Alzheimer's & Dementia.
Lilly shares closed Tuesday down 2.5% to $85.72, ahead of Wednesday's data. However, shares of the pharmaceutical giant are up 24% this year, due in large part to investor excitement about the Alzheimer's program and high expectations for positive solaneuzumab (sola, for short) study results.
In an extended analysis of two large but negative clinical trials, Lilly scientists conclude that mild Alzheimer's patients who start treatment with sola early lose cognition and function at a slower rate than similar patients who start taking the drug later. The inability of "delayed-start" sola patients to catch up to early sola starters suggests the drug is having a positive, modifying effect on Alzheimer's, Lilly says.
Using a delayed-start trial design to assess the potential for a drug to slow disease progression has been tried before, but the sola results are the first time it's been used successfully with Alzheimer's patients, says Hong Liu-Seifert, the Lilly scientist who led the EXPEDITION-EXT study.
"The results support the potential benefit of starting treatment with solanezumab earlier rather than later in disease progression, and suggest there is persistence of treatment effect after the delayed-start patients are given the drug," said Dr. Paul Aisen, director of the Alzheimer's Therapeutics Research Institute at the University of Southern California, in a statement.
But not all Alzheimer's experts share Lilly and Aisen's optimistic view of the sola delayed-start data. An Alzheimer's doctor at the AAIC conference, who asked not be named because he didn't want to criticize colleagues publicly, views the small differences in measurements of cognition and function between early- and delayed-start sola patients to be clinically meaningless.
He also believes Lilly leaned heavily on extensive "modeling" of the raw data and unproven but generous statistical methods to reach its positive conclusions. "What we're seeing here is not a disease modifying effect," he says.
In the EXPEDITION-EXT study, mild Alzheimer's patients who received sola in the failed EXPEDITION 1 and 2 studies for 18 months continued on the drug for another two years. The mild patients treated originally with placebo crossed over to treatment with sola, also for two years. Would the treatment benefit in cognition and function seen in sola-treated patients compared to placebo patients persist even after all patients were taking the drug?
Lilly says yes. Six months into the extension study and based on a pre-defined statistical margin, the cognitive and function measures for early-start sola patients were preserved compared to delayed-start patients. The treatment difference was maintained through one year.
The following chart from the EXPEDITION-EXT study being presented Wednesday tracks changes over time on the ADAS-Cog14, a measure of cognition used with mild Alzheimer's patients. At 108 weeks (six months into the extension study), the early-start sola patients scored 1.75 points higher on the ADAS-Cog14 test compared to delayed-start patients. At 132 weeks (one year into the extension study), the treatment difference between the groups is 1.91 points on the ADAS-Cog14 test. These are small improvements suggesting sola is slowing Alzheimer's disease progression, although critics call the findings clinically marginal or meaningless.
"What I believe we've shown is placebo patients lose more brain cells to the degenerative process of Alzheimer's, so even when they're switched over to [sola], they can't catch up because they've lost brain cells that can never come back. This is why the [sola] treatment difference persists," says Eric Siemers, another Lilly scientist involved in the study.
Siemers acknowledges some limitations and weaknesses to the sola study conclusions, most notably that the delayed-start analysis was retrospective and hinged on data from two negative studies. The conclusion that delayed-start sola patients aren't catching up to early treaters might simply be statistical noise.
Dr. Maria Carillo, chief science officer for the Alzheimer's Association, views Lilly's EXPEDITION-EXT results with cautious optimism.
"I think the data show hopefulness for the approach... but you can't draw too many conclusions," Carillo says. "This is not a blockbuster cure, but it may be slowing down the decline" in Alzheimer's patients, she adds.
Lilly's sola is an antibody targeting beta amyloid, a sticky protein that clumps together to form nerve-deadening plaques in the brain. Scientists have long assumed sopping up beta amyloid in the bloodstream and removing amyloid plaques from the brain should improve cognition, memory and function in Alzheimer's patients.
Unfortunately, the "beta amyloid hypothesis" has fallen short in clinical trials. To date, none of the amyloid-targeting antibodies have been able to demonstrate a significant cognitive or functional benefit compared to placebo in phase III clinical trials involving thousands of Alzheimer's patients.
Despite all the setbacks, the development of beta amyloid antibodies persists because of evidence suggesting the drugs might still benefit patients at the earliest stages of Alzheimer's. Current clinical trials of amyloid-targeting antibodies enroll patients with prodromal and mild Alzheimer's disease. The thinking goes that blocking beta amyloid before it causes significant loss of cognition and memory might produce significantly better (disease modifying) results.
Biogen (BIIB - Get Report) stoked renewed investor interest in Alzheimer's with its antibody adacanumab following positive results from a small phase I study presented in March. Updated results from this study are also being presented Wednesday at the AAIC meeting.
The Internet dress turned out to be blue and black. Those who saw white and gold were fooled by their brains.
We won't have a definitive answer about Lilly's solanezumab until late next year, when results from the large phase III study EXPEDITION-3 are released. Biogen only just started a phase III study of aducanumab, so results are still years away.