Roche announced Wednesday that it will halt two Phase III studies of crenezumab in patients with early sporadic Alzheimer's disease after a pre-planned interim analysis indicated that the trials were unlikely to meet their primary endpoints. Shares in AC Immune, which discovered the anti-beta-amyloid molecule, fell more than 50 percent on the news.
Both the CREAD 1 study, which was started in early 2016, and the CREAD 2 trial, which was initiated in mid-2017, evaluated the efficacy and safety of crenezumab in 750 patients with early Alzheimer's disease with confirmed evidence of cerebral beta amyloid pathology. The trials' main goal was change from baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score.
According to Roche, the interim analysis conducted by the independent Data Monitoring Committee did not identify any safety signals for crenezumab and the overall safety profile was similar to that seen in previous trials. Data from the studies is expected to be presented at a future medical meeting.
"While the results with crenezumab are disappointing, they meaningfully contribute to our understanding of Alzheimer’s disease," remarked Sandra Horning, head of global product development at Roche. Crenezumab continues to be studied in the Alzheimer's Prevention Initiative (API) trial, which includes cognitively healthy individuals in Colombia with an autosomal dominant mutation who are at risk to develop familial Alzheimer's disease.
Horning said that despite the setback, Roche "will continue our Phase III GRADUATE trials with gantenerumab and Phase II TAURIEL trial with the anti-tau molecule RG6100, as well as our imaging and fluid-based diagnostic solutions." Gantenerumab is an experimental IgG1 monoclonal antibody designed to bind to aggregated forms of beta-amyloid, while RG6100, which is also part of the company's collaboration with AC Immune, is an investigational monoclonal IgG4 antibody that binds to multiple tau species.
The failure of the CREAD 1 and 2 studies follows a growing number of development setbacks in Alzheimer's disease, with Eli Lilly and partner AstraZeneca last year halting Phase III trials of the BACE inhibitor lanabecestat as they were not likely to meet their primary endpoints.
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