Charities have registered their disappointment after an experimental drug failed to live up to its promise in trials as a potential treatment for Alzheimer’s disease.
Eli Lilly announced today that their drug solanezumab, which has previously attracted extensive media coverage, had failed to meet its primary target in trials of slowing cognitive decline in patients with mild Alzheimer’s disease.
“We shouldn’t view this setback as the end of the line”
The phase III trial, called EXPEDITION 3, was started in 2013 after the same drug failed to meet its primary endpoints in two earlier clinical trials in mild to moderate Alzheimer’s.
However, further analysis of the earlier trials showed a slowing of cognitive decline in only those volunteers with mild Alzheimer’s. The findings at that time were encouraging enough to support the drug going back into another phase III trial in people only in the mild stages of the disease.
Unlike previous trials with the drug, EXPEDITION 3 used amyloid PET brain scans or spinal fluid tests to select only those patients with high levels amyloid who were most likely to respond to the drug.
Solanezumab is one of several drugs in development that are designed to target amyloid – a key protein that builds up into “plaques” early in the brain in Alzheimer’s disease.
The drug is a monoclonal antibody designed to tag single amyloid molecules circulating in the blood and the brain, mopping them up to prevent more plaques forming.
If it had been successful, it would have been the first new treatment for dementia since 2003, and the first to slow the progression of Alzheimer’s.
“We had high hopes for this drug to become the first to slow down Alzheimer’s disease”
EXPEDITION 3 was a multinational, 18-month placebo-controlled trial in over 2,100 people with mild Alzheimer’s disease.
The headline results showed the drug did not cause a statistically significant slowing in memory and thinking decline compared to a placebo treatment, as measured by the ADAS-Cog14 cognitive test.
While Lilly reported that several of the secondary measurements being taken in the trial showed a signal in the right direction, these were much smaller than hoped for.
As a result, Lilly said in its press statement that it would not be submitting the drug for regulatory approval for the treatment of mild Alzheimer’s.
However, the drug is currently planned to enter another trial for an even earlier stage of the disease called “prodromal Alzheimer’s”, where patients have early memory and thinking problems not severe enough to be classed as dementia, but who have signs of amyloid on PET scans and in spinal fluid.
Dr David Reynolds, chief scientific officer at Alzheimer’s Research UK, said: “Our 15-year wait for a new Alzheimer’s drug does not end today, but we shouldn’t view this setback as the end of the line.
“It’s very disappointing that solanezumab has not shown benefit for people with mild Alzheimer’s and will no doubt trigger important debate within the research community,” he said.
“Solanezumab is designed to mop up amyloid protein and is the result of years of development based on the concept that this protein is a central driver of the disease,” noted Dr Reynolds.
He added: “While today’s results are a setback for the amyloid hypothesis, there are several other anti-amyloid drugs still in clinical trials that work in different ways, some of which are being tested even earlier in the disease process than solanezumab.”
Jeremy Hughes, chief executive of Alzheimer’s Society, said: “After positive news last summer, we had high hopes for this drug to become the first to slow down Alzheimer’s disease. It’s extremely disappointing to learn that it hasn’t delivered a meaningful change for people living with dementia.
“We’ve seen time and again that developing effective treatments is incredibly difficult,” he said. “This is only one drug of several in the pipeline and they aim to tackle dementia in different ways, so we should not lose hope.
“There will be concern that investment in dementia research may drop as a result of another failure – neither families nor the NHS can afford for this to happen. We must and will redouble our efforts and investment into dementia research,” he added.