Following the failure of a trial for two monoclonal antibody drugs for Alzheimer’s disease (AD), Eli Lilly’s solanezumab and Roche’s gantenerumab, in patients that have a rare genetic mutation that causes early-onset AD;

Alessio Brunello, Senior Pharma Analyst at GlobalData, a leading data and analytics company, offers his view:

“The data from the trial DIAN-TU that tested solanezumab by Eli Lilly and gantenerumab by Roche presented disappointing results in some earlier studies, but the doses in this study ranged up to four to five times higher and researchers had hoped that would prove more effective as was seen with Biogen’s aducanumab. However, in the DIAN-TU the very small sample size and the late increase of doses affected the results of the trial and will most likely show some positive signals to emerge in the full results that will be presented in April at AAT-AD/PD in Vienna.

“DIAN-TU was a preventative trial in subjects with a rare inherited form of early-onset dementia called autosomal-dominant AD (ADAD.) As these individuals show signs of degeneration at a predictable age, researchers hoped to have clinical efficacy in a small number of the population. However, the study was determined not to have achieved its primary endpoint, and Eli Lilly stated that it would not pursue the submission of the drug for approval to treat people with dominantly inherited AD.

“GlobalData forecasted global sales of solanezumab to be equating to $296m in 2024 in the seven major markets (*7MM) while global sales of Roche’s gantenerumab are expected to reach $55m in 2025 in the 7MM, due to the lack of efficacy in clinical trials. These low figures are explained by the numerous studies of drugs that clear amyloid that have failed to show clinical benefit, casting doubt on the amyloid theory of AD and the potential to be successful clinically and commercially.

“Key opinion leaders (KOLs) interviewed by GlobalData explained that what is remaining with solanezumab is the A4 study, which targets preclinical participants, cognitively normal people with amyloid accumulation. This target may be particularly appropriate for treatment with solanezumab. However, for gantenerumab, the KOLs believe the drug has a lot of similarities with aducanumab. It was tested in two studies in people with early symptomatic AD where it did not seem to be effective for the total study group. However, in a subgroup of people that reached higher plasma concentrations, it seemed it had a clinical signal and also good target engagement. An increased dose of gantenerumab is currently being studied in two trials, GRADUATE 1 and 2 that target early symptomatic AD patients, so MCI and mild AD and results are expected in 2022.”