Contributed by Joshua D. Grill, PhD, Director of UCI MIND
Early Monday morning (February 10, 2020), the Dominantly Inherited Alzheimer’s Network Trials Unit (DIAN-TU) and Eli Lilly & Company announced disappointing results from a clinical trial of the monoclonal antibody, solanezumab, against the beta amyloid protein that accumulates in the brain of people with Alzheimer’s disease (press release >). The DIAN includes only the rare families who carry genetic mutations that cause an early-onset (3rd, 4th, 5th decade of life) form of Alzheimer’s disease. Solanezumab is also being tested as part of the Anti-Amyloid treatment in Asymptomatic Alzheimer’s (A4) Study, which is ongoing at UCI MIND.
Without question, the results are disappointing. Solanezumab did not delay cognitive decline in people who carried mutations that cause autosomal dominant Alzheimer’s disease. The results must be taken at face value. A small number of people (about 50) were exposed to solanezumab in the DIAN-TU study (compared to more than 500 in A4). Like in A4, there was a dose adjustment mid-study, quadrupling the dose of solanezumab, but in DIAN-TU this adjustment came much later in the trial, limiting the total exposure to the higher dose. Also, in DIAN-TU, not all participants were cognitively normal. Unlike the A4 Study in pre-symptomatic participants only, DIAN-TU participants could have mild cognitive impairment or even some functional impairment and still participate (trial details >). It is possible that the DIAN-TU trial would not have shown whether solanezumab worked in very early disease (before symptom onset).
The results are not anticipated to impact the ongoing A4 Study, which is expected to finish the double-blind portion in 2022. If anything, this news further emphasizes the critical importance that participants complete the A4 Study. Previous studies of solanezumab in symptomatic patients with Alzheimer’s disease suggested that earlier and longer treatment would be essential if solanezumab was going to have a clinical benefit. No matter what, both DIAN-TU and A4 will provide valuable learnings to the field, learnings made possible by the people participating in (and completing) these studies.