Genentech and Eli Lilly announced results from the phase 2/3 Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) Study. The study tested two therapies compared to placebo, Genentech and Roche’s gantenerumab and Eli Lilly and Company’s solanezumab. Neither of the therapies reached the primary endpoint, which was the DIAN-Multivariate Cognitive Endpoint (DIAN-MCE). This endpoint includes the Wechsler Memory Scale-Revised Logical Memory Delayed Recall, Cogstate International Shopping List Test, Wechsler Adult Intelligence Scale-Revised Digit Symbol Substitution Test, and the Mini Mental State Examination.
DIAN-TU-001 was sponsored by Washington University School of Medicine in St. Louis, United States. The study tested two investigational therapies compared to placebo (Genentech and Roche’s gantenerumab and Eli Lilly and Company’s solanezumab) to determine if either of these treatments could slow the rate of cognitive decline and improve disease-related biomarkers in people who are known to have a genetic mutation for inherited AD. The study followed 194 participants for up to 7 years; the average was about 5 years. All subjects came from families that carry a genetic mutation that causes inherited AD. The small study included people who did not yet have symptoms of AD at the time of enrollment as well as people who already had mild symptoms of the disease.
The most common adverse events reported more frequently with gantenerumab than placebo were injection-site reactions, infection of the nose and throat (nasopharyngitis), and amyloid-related imaging abnormalities (ARIA), manifesting as cerebral edema or microhemorrhages.
Solanezumab is an anti-amyloid monoclonal antibody being studied in the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) Study. The A4 Study is a clinical trial testing solanezumab in older individuals who have evidence of amyloid in their brains, but do not show symptoms of memory impairment.
Gantenerumab is designed to bind to aggregated forms of beta-amyloid and remove beta-amyloid plaques, a pathological hallmark of AD thought to lead to brain cell death. Previous clinical studies of gantenerumab showed beta-amyloid plaque lowering in people with the more common form of AD that is not directly caused by gene mutations. Two Phase III studies (GRADUATE 1 and 2) are currently underway to assess gantenerumab for the treatment of people with sporadic AD. The GRADUATE program is currently enrolling more than 2,000 patients in up to 350 study centers in more than 30 countries worldwide.Source: Genetech