Top-line results from Roche’s Phase II/III DIAN-TU-001 clinical trial of gantenerumab showed that the drug failed to meet its primary goal in patients with an early-onset, inherited form of Alzheimer’s disease (AD).
Called autosomal dominant AD (ADAD), this form of inherited Alzheimer’s comprises less than 1% of all cases of the disease.
Gantenerumab is an investigational drug that attaches to aggregated beta-amyloid, which is a pathological hallmark of the disease, and eliminates the beta-amyloid plaques.
Funded by Washington University School of Medicine in St Louis, US, DIAN-TU-001 assessed gantenerumab and Eli Lilly’s solanezumab for their ability to slow the cognitive decline rate and improve disease biomarkers.
The trial involved follow-up of 194 participants for up to seven years. The Gantenerumab treatment arm involved 52 patients.
The primary outcome of the study was the DIAN Multivariate Cognitive Endpoint, which is a new measure to determine cognitive performance in ADAD patients.
Compared with placebo, Roche’s drug did not lead to a significant slowing of the cognitive decline rate while failing to meet the primary goal.
Gantenerumab’s safety profile during the trial was consistent with previous data. The investigators did not report any new safety signals.
Roche chief medical officer and global product development head Levi Garraway said: “Although DIAN-TU didn’t reach its primary endpoint, the trial represents the first of its kind and a bold undertaking by all partners involved.
“Given its experimental nature, we are unable to draw firm conclusions about the impact of gantenerumab in autosomal-dominant Alzheimer’s disease. This outcome does not reduce our confidence in the ongoing Phase III GRADUATE clinical programme.”
The GRADUATE programme of the drug involves two Phase III trials in a broader Alzheimer’s population.
Apart from gantenerumab, Roche is developing semorinemab in Phase II trials for sporadic AD, and crenezumab also continues Phase II trial for ADAD.
The company announced the discontinuation of gantenerumab’s SCarlet RoAD study in Alzheimer’s in 2014.