- AC Immune on Wednesday said its experimental drug semorinemab failed to slow cognitive and functional decline in Alzheimer's disease patients compared to those on placebo in a mid-stage trial run by partner Roche. U.S.-listed shares in the Lausanne, Switzerland-based company fell by more than 40%.
- The biologic drug aimed to stop accumulation in the brain of a protein called tau that is linked to the neurodegenerative decline characteristic of Alzheimer's. This approach is seen as a newer alternative to the dominant, albeit controversial, "amyloid hypothesis," which blames the disease on the buildup of clumps of amyloid protein.
- Alzheimer's disease has proven challenging to drug developers, with the last new treatment for the condition approved in 2003 and none available that can slow its debilitating march. Researchers have spent years testing the amyloid hypothesis without an approved drug to show for it, though Biogen's aducanumab has a chance to break that trend.
Until Biogen's surprising and controversial finding that the highest tested dose of its amyloid-blocking drug aducanumab slowed Alzheimer's patients' decline, every treatment targeting the characteristic amyloid tangles had failed.
These setbacks have come in patients ranging from the moderately impaired to those at high risk before symptoms emerge, causing many Alzheimer's experts to doubt the idea that amyloid is the main culprit in the disease.
With the failures of amyloid-targeting drugs, attention has shifted to tau, and many companies, including Biogen, Eli Lilly and AbbVie, have poured money into the effort. AC Immune, which also partnered the amyloid-targeting drug crenezumab with Roche, was among the leaders in tau research. Semorinemab is the most advanced of the group, making its failure — which isn't the first for a tau-targeting medicine — notable.
"This is clearly disappointing news for the company and for the Alzheimer’s community given that tau has been increasingly viewed as a promising target for treating [Alzheimer's], and investors ... have been focused on this event to potentially validate the anti-Tau antibody approach," wrote SVB Leerink analyst Marc Goodman in a note to investors.
Roche's TAURIEL trial tested three doses of semorinemab against a placebo in 457 people with mild symptoms, looking for signs that it could slow decline in cognition or function on three separate measurements. After more than a year of follow-up, researchers found no statistically significant difference between the patients taking semorinemab and those given a placebo.
The drug's failure is a stinging setback for AC Immune, which has committed heavily to the tau hypothesis. It boasts a pipeline with two other experimental tau-fighting treatments for Alzheimer's — a vaccine partnered with Johnson & Johnson and an oral drug partnered with Eli Lilly. In addition, Roche has another trial of semorinemab underway in moderately affected Alzheimer's patients.
The vaccine advanced into a higher dosing group following an interim analysis of a Phase 1/2 trial conducted by J&J, while AC Immune expects initial data from a Phase 1 trial of the oral drug by year's end.