Clinical trials have provided some preliminary evidence that drugs targeting amyloid may help delay Alzheimer’s disease (AD), although scientists stress it is far too early to draw conclusions.
The EXPEDITION study generating headline around the world concerns Eli Lilly’s solanezumab, a drug designed to destroy the amyloid plaques that are characteristic of AD that failed to show an impact in a phase III clinical trial reported in 2012.
Now, an analysis of data from this and other prior studies of solanezumab suggest that patients treated earlier with the antibody saw their rate of cognitive decline reduced by around a third compared to those who started treatment later.
Lilly says it is excited by the results reported at the Alzheimer’s Association International Conference (AAIC), although it stressed the findings are not in themselves evidence of efficacy but rather back up the ‘delayed-start’ design used another study – EXPEDITION 3 – that is testing the drug in mild AD patients.
EXPEDITION 3 will compare patients who take the drug from the outset to a placebo group that will subsequently switch to solanezumab, reproducing the analysis presented at the AAIC in a more rigorous, prospective study. It is due to complete in October 2016.
Nevertheless, company scientists have suggested the trial is the first evidence that solanezumab can have some impact on the underlying pathology in AD, unlike current drugs which treat symptoms of the disease but have no impact on its progression.
Roche also had updated results from a previously-reported trial of its gantenerumab candidate that failed to show a benefit on cognition. The new analysis concludes that the drug was able to reduce amyloid in the brain and suggests that a higher dose may be required to see any clinical effect.
The trial was terminated earlier this year after it became clear it would not be able to show any benefit, but remains in active development, according to Roche, which also has another amyloid-targeting drug called crenezumab heading into phase III testing after mixed results in earlier trials.
Meanwhile, data from a phase Ib trial of Biogen’s aducanumab has revealed that the drug was able to achieve a sizeable reduction in beta amyloid in the brains of people with mild or prodromal AD, but was unable to achieve any significant impact on cognitive decline over the course of a year.
However, there was a non-significant slowing of cognitive decline that seemed to be dose-dependent, according to Biogen, once again giving a pointer that amyloid therapy might have some impact if delivered early enough.
On the downside, the treatment was associated with headaches and abnormalities in brain scans that will have to be monitored closely. The trial still has another two years to run.
The Alzheimer’s Society in the UK welcomed the new data – which it described as the “first hints” that amyloid therapies may slow the disease.
“After a decade of no new therapies for dementia, today’s news is an exciting step forward,” said Dr Doug Brown, the organisation’s R&D director.
“We will have to wait for the ongoing trials to finish to know the full risks and benefits of these drugs.”