Indianapolis-based Eli Lilly is doubling down on its anti-Alzheimer’s disease efforts. Even though a high-profile Alzheimer’s drug failed its most recent trial, the pharma giant is still holding out hope the science behind the therapy can work.
Solanezumab would have been a Prozac-style blockbuster for Lilly. Instead, a late-stage clinical trial found it didn’t work the way scientists hoped.
Lilly hoped the drug, which targets sticky proteins in the brain called amyloids—would slow the effects of Alzheimer’s in patients with mild dementia. Scientists posit these proteins are responsible for the effects of the disease, but the drug’s failure cast doubt on that hypothesis.
Still, during a discussion of the results during the annual Clinical Trial on Alzheimer’s Disease conference in San Diego Thursday evening, Alzheimer’s researcher and Lilly collaborator Paul Aisen said there was a decline in symptoms, just not enough of one to officially call the trial a success.
“Even though the trial is a negative trial, it’s supporting a treatment effect for Sola, and it’s confirmatory for the amyloid treatment hypothesis,” Aisen said. “In fact, I think this is the strongest confirmation to date.”
The main measure of the study concerned a reduction in cognitive decline as measured through the Alzheimer’s Disease Assessment Scale-Cognitive subscale. After 80 weeks, patients treated with Solanezumab showed an 11 percent reduction in decline compared with patients who took a placebo. Even though the drug performed better than the placebo, Lilly was hoping to see three times the effect.
Similar results were found using other secondary measures of cognitive decline.
Functional results-- which refer to how well a person can perform, for example, daily living activities—were less conclusive. The original plans for the study called for a study of these functional measures, but in March, the company scaled back the study in this area, citing recent findings that stated cognitive decline in Alzheimer’s patients “preceded and predicted” functional decline.
That the drug affected cognitive function—even minimally—raised questions about the amount patients took. Lilly said it’s possible the drug could be more effective in higher doses or in patients with less advanced forms of the disease.
Other scientists say all the study confirms is one particular drug in one particular dose didn’t work in a particular type of patient.
Brown University neuroscience professor Stephen Salloway, who was among the CTAD audience, warned Lilly against wishful thinking.
“We all share the same goal—the urgency of finding breakthrough treatments,” said Brown during a question-and-answer session following the panel. “[My concern is] we over-read exploratory or secondary outcome measures and enlarge on them beyond the information they provide.”
Alzheimer’s Association Chief Science Officer Maria Carillo said to not rule any therapies out yet. After all, she said, there are other similar therapies to solanezumab that may be more effective in treating amyloid plaques.
“It’s not a time to sit back and say ‘not tractable,’ or that the amyloid hypothesis, for example, has been the wrong pathway,” she said.
Carillo added, however, researchers shouldn’t rule out other treatment hypotheses.
In the meantime, Lilly announced Friday it was pairing with the European firm Astrazeneca to develop another amyloid blocker.