Bristol-Myers Squibb (BMS) has become the latest company to end development of an amyloid-targeting Alzheimer’s drug candidate, following the termination of the trial programme for avagacestat.
The pharma company said that results from phase II trials investigating the compound “did not establish a profile that supported advancement to phase III development”, bringing an end to hopes for the drug as a vital breakthrough in Alzheimer’s treatment.
Issues with avagacestat’s efficacy were noted by BMS as the reason for pulling development, with no new safety issues emerging during the latest analysis of phase II data.
Other researchers will have the opportunity to learn from avagacestat’s failings next year, with BMS due to share this phase II data at a scientific forum during 2013.
It is the latest in a number of trial disappointments involving drugs that target amyloid beta, which is deposited in the form of plaque in the brains of people with Alzheimer’s.
In August, 2012, Pfizer and Johnson & Johnson ended their programme to investigate bapineuzumab after phase III trials showed it provided no cognitive or functional benefit in patients with mild-to-moderate Alzheimer’s disease.
This was shortly followed by an announcement from Lilly that its amyloid-targeting antibody solanezumab failed to show a significant benefit in patients with Alzheimer’s disease.
However, both compounds target amyloid plaque once it has already built up, and there are hopes that treatments that target the condition earlier on could be effective.
This include Merck & Co’s candidate MK-8931, which recently became the first beta-amyloid precursor protein site-cleaving enzyme (BACE) inhibitor to reach phase II/III development.
The BACE inhibitor class of therapies cut amyloid precursor protein (APP), interrupting the formation of beta amyloid and preventing the formation of the amyloid plaques.
Other companies also pinning their hopes on BACE inhibitors include Lilly, Roche and Eisai.
BMS has not given up on its Alzheimer’s programme either, and said it will continue to test the amyloid hypothesis with an investigational gamma secretase modulator in phase I development.