An artistic impression of amyloid plaques in Alzheimer’s disease [Adobe Stock]
“We’re talking about studies with sometimes two thousand people per phase three clinical trial in Alzheimer’s,” said Charles Fisher, CEO of Unlearn, a company developing digital twins to streamline clinical trials. The phase 3 trial for solanezumab from Eli Lilly that completed in 2016 had 2,100 participants. More recently, the Clarity AD Phase 3 trial for lecanemab from Biogen and Eisai enrolled 1,795. Enrolling such large volumes isn’t a small undertaking. “Individual phase 3 clinical trials can cost hundreds of millions of dollars,” Fisher said.
The complexities of Alzheimer’s trial recruitment
The need for such large trials stems from a fundamental challenge: “Even though [Alzheimer’s] is really common, it’s actually really difficult to fully enroll those studies because you need so many participants coming from an elderly population that you don’t want to have too many comorbidities,” Fisher said.
Charles Fisher, Ph.D.
“When you start a clinical trial and you don’t exactly know what to expect, you can make some mistakes,” Fisher said. Some trials focused on amyloid-lowering drugs encountered problems with dosing or side effects, leading to the need to make midstream adjustments. Such challenges underscore the need for novel approaches to optimize the trial process.
Digital twins offer hope for streamlining Alzheimer’s research
A pair of studies presented at the Alzheimer’s Association International Conference 2024, held July 28 to August 1, highlighted the potential of digital twins to optimize Alzheimer’s clinical trials. In a collaboration with Johnson & Johnson Innovative Medicine, Unlearn showed that incorporating participants’ digital twins could reduce control arm sizes by 33% when estimating the treatment effect on Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11-item (ADAS-Cog11) at 18 months or by 19% when estimating the effect on Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) at 12 months in Phase 3 studies. Additionally, digital twins could boost power by up to 10%.
The significant costs of Alzheimer’s research, with phase 3 trials often reaching budgets of a quarter-billion dollars, are a significant hurdle in the field. Unlearn presented two studies at the Alzheimer’s Association International Conference 2024 highlighting the potential of digital twins to chip away at such costs while optimize Alzheimer’s clinical trial design. In collaboration with Johnson & Johnson Innovative Medicine, results showed that incorporating digital twins could cut control arm sizes by up to 33% in phase 3 studies, potentially saving tens of millions of dollars per trial. A separate study with AbbVie demonstrated that digital twins could reduce overall sample sizes by 10–15% in phase 2 studies, offering similar cost savings and potentially accelerating the pace of research.
Beyond the substantial cost savings achieved through smaller sample sizes, digital twins promise faster enrollment, shorter trial durations, and potentially, faster access to potentially life-changing treatments for patients. “Anything that we can do to streamline, to decrease the cost of those studies, decrease the timeline, we think all of that is really important in areas like Alzheimer’s,” Fisher said.
Filed Under: machine learning and AI, Neurological Disease
