Roche dents the amyloid hypothesis again

With some big late-stage readouts due in Alzheimer’s disease in the coming year, Roche and AC Immune have reminded investors of the perils of this space. True, hopes were not high for the anti-amyloid MAb crenezumab, which had already flunked the pivotal Cread studies several years ago. But the latest failure, of a mid-stage trial in presymptomatic patients with a specific mutation, could make the likes of Lilly, Biogen – and indeed Roche – nervous. Roche and AC Immune are not saying much about the data, although the partners appear to disagree about whether numerical differences favouring crenezumab were “small” or not. More details are due at the AAIC meeting on August 2. The latest flop hits the theory that intervening early could halt Alzheimer’s, though the amyloid debate will rumble on, particularly as crenezumab has not been shown to reduce amyloid plaques. This has been seen with Roche’s gantenerumab, Lilly’s donanemab and Biogen/Eisai’s lecanemab. Whether plaque reduction has an impact on Alzheimer’s symptoms remains to be proven, something that pivotal data with these projects will hopefully help clarify.