Top-line results from the Phase II PIONEER trial of oral T3D-959 for the treatment of people with mild-to-moderate Alzheimer’s disease (AD) were presented by T3D Therapeutics at this year’s Clinical Trials in Alzheimer’s Disease (CTAD) conference, held in October in Boston. PIONEER was a Phase II randomised, placebo-controlled and multi-center trial evaluating the efficacy and safety of T3D-959 in people with mild-to-moderate AD. 250 participants received either placebo or T3D-959 orally once a day for 24 weeks. Three doses of T3D-959 were tested (15, 30 and 45 mg). The Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog11) and the Clinical Global Impressions of Change (CGIC) were the two primary endpoints of the study and they were not met in the overall population.
Clinical evidence of improvement in cognition was shown in a sub-group of participants, those who had a high baseline pTau-217 ratio. The secondary endpoint, plasma Ab42/40 ratio change, was met in the group receiving T3D-959 30mg. The effect was similar to lecanemab at 6-months. In the high pTau-217 ratio group the improvement of Ab42/40 ratio was nearly 2-fold greater than the overall group. T3D-959 30-mg treatment in the overall population significantly improved the neurodegeneration biomarker neurogranin, as well as biomarkers of inflammation and metabolism. In addition, the experimental drug was generally well tolerated.
