John Didsbury, PhD, T3D Therapeutics, Research Triangle Park, NC, discusses findings from the Phase II PIONEER trial (NCT04251182), evaluating the safety and efficacy of three doses of oral T3D-959 over 24 weeks versus placebo in patients with mild-to-moderate Alzheimer’s disease (AD). T3D-959 is a small molecule PPAR delta/gamma dual nuclear receptor agonist that corrects insulin resistance in AD to improve glucose and lipid metabolism in the brain. Despite evidence of peripheral and central target engagement, the drug failed to improve cognition and function. Additionally, a surprisingly strong placebo effect was observed. Dr Didsbury emphasizes that 45% of participants did not meet the threshold for blood p-tau217 ratio determined as indicative of underlying AD pathology, suggesting these patients had been misdiagnosed with AD. In the subgroup of patients with a p-tau217 ratio above the cut-off, there was an improvement in cognition, reduction in plaque burden, and correction of dysregulated metabolic pathways in response to T3D-959. These findings suggest T3D-959’s potential as an orally available AD treatment, guiding inclusion criteria and optimal dosing in future Phase III trials. This interview took place at the CTAD 2023 conference in Boston, MA.
These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.
