Eli Lilly's gamble on amyloid-busting drug solanezumab for mild Alzheimer's has failed, and the drugmaker has made the painful decision to abandon the drug.
The results of the EXPEDITION3 trial in patients with mild Alzheimer's disease showed no significant slowing in cognitive decline compared to placebo, although there were some glimmerings of a benefit, said Lilly.
That mirrors the findings with the drug in more advanced Alzheimer's dementia that were reported back in 2012 and adds to an increasing body of evidence that trying to treat the disease with amyloid-targeting drugs may be futile.
Solanezumab joins a very long list of failed drugs have sought to treat Alzheimer's by preventing the formation of the amyloid plaques that are characteristically seen in the brains of patients with this form of dementia.
When solanezumab and other drugs such as Pfizer's bapineuzumab and Roche's gantenerumab failed to show a benefit in patients with established Alzheimer's dementia, clinicians suggested that giving them earlier could be the key to unlocking their efficacy.
However, the latest failure lends weight to suggestions that amyloid deposits are a trigger for other pathologies in the brain and become irrelevant once those mechanisms come into play.
The role of amyloid—and the impact on other companies developing amyloid-busting drugs like Merck & Co, Amgen/Novartis and Biogen—is likely to dominate discussions when Lilly presents the results of EXPEDITION3 at the Clinical Trials on Alzheimer's Disease (CTAD) meeting on December 8.
Lilly has confirmed that it will not seek marketing approval for solanezumab as a treatment for mild dementia due to Alzheimer's disease, and Chief Executive John Lechleiter said the company would "evaluate the impact of these results on the development plans for solanezumab and our other Alzheimer's pipeline assets."
Along with a recently started trial of solanezumab in even earlier-stage (prodromal) Alzheimer's, that includes AstraZeneca-partnered BACE inhibitor AZD3293, which is in Phase III testing. The latter drug works upstream of solanezumab by inhibiting an enzyme involved in the conversion of amyloid precursor protein (APP) into amyloid beta.
While solanezumab was clearly a long shot for Lilly, the lure of what some analysts suggested could be as much as $5 billion in sales potential for a drug that can tackle the underlying disease mechanism in Alzheimer's proved to be very strong.
Lilly has said it would take a $150 million charge in the fourth quarter as a result of the setback, although this is estimated to be only a fraction of its total spend on the drug.
Analyst Geoffrey Porges of Leerink Research said that the finding is "a serious blow" for Biogen and other companies in the Alzheimer's field, even though Biogen's aducanumab is "a materially different antibody, in a different trial, at a different dose, and in different patients, than solanezumab."
Shares in Lilly were down almost 14% premarket at the time of writing.
Commenting on the news, Dr. David Reynolds, chief scientific officer at Alzheimer's Research UK, told FierceBiotech that the 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—the journey towards a new treatment can and will continue."
"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. We can't disregard these ongoing trials and their findings will now be more important than ever in shaping the search for disease-modifying treatments for Alzheimer's."