Topline data were announced from the phase 2/3 DIAN-TU study of solanezumab (Eli Lilly) and gantenerumab (Genentech) in patients at risk for or with dominantly inherited Alzheimer disease.
Solanezumab and gantenerumab are investigational humanized monoclonal antibodies that are designed to increase clearance of soluble amyloid beta (Aβ) from the brain by binding to aggregated forms of Aβ. The randomized, double-blind, placebo-controlled DIAN-TU study enrolled 490 patients to assess the efficacy and safety of these investigational agents to determine if either of these treatments could slow the rate of cognitive decline and improve disease-related biomarkers.
Patients were randomized to 1 of 4 treatment arms that included: intravenous infusion of solanezumab (n=50) or subcutaneous injection of gantenerumab every 4 weeks (n=52) at escalating doses, compared with their matching placebos. The primary end point of the study was change in the DIAN-TU cognitive composite score, a novel outcome measure designed to assess cognitive performance in patients with or at risk for autosomal dominant Alzheimer disease.
Results showed that both solanezumab and gantenerumab did not meet the primary end point. Additional secondary end points and biomarkers are still being investigated. Full study data will be presented at the Advances in Alzheimer and Parkinson Therapies (AAT-AD/PD) Focus Meeting in April 2020.
Eli Lilly has decided not to move forward with regulatory submission for solanezumab in the treatment of dominantly inherited Alzheimer disease. The Company noted that these results do not impact the ongoing investigation of solanezumab in preclinical Alzheimer disease in the Anti-Amyloid Treatment in Asymptomatic Alzheimer (A4) Study.
Additionally, Genentech and Roche are conducting further analyses to understand data from the DIAN-TU study. The safety profile of gantenerumab was consistent with that observed in previous studies. The Company plans to continue its ongoing phase 3 studies (GRADUATE 1 and 2) of gantenerumab in patients with Alzheimer disease that is not directly caused by gene mutations.