Abstract Buntanetap is an orally available small RNA targeting molecule that inhibits the translation of multiple neurotoxic aggregating proteins, including amyloid precursor protein (APP) and Tau. It has been evaluated in 13 clinical trials involving over 1000 participants, including healthy volunteers, patients with Alzheimer’s disease (AD) and Parkinson’s disease (PD), and has shown a favorable safety and tolerability profile. In two small studies in early AD, buntanetap demonstrated a trend toward cognitive improvement, despite being underpowered for efficacy. In a Phase2/3 study in early PD, it also improved PD patients’ cognitive functions. We evaluated safety and efficacy of buntanetap in treating mild to moderate AD patients in this 3-month randomized double-blind dose-ranging study (NCT05686044). Total of 351 Patients were equally randomized to either 7.5 mg, 15 mg, 30 mg buntanetap or placebo. Buntanetap had a favorable safety profile. The study did not meet its primary endpoints (ADAS-Cog-11 and ADCS-CGIC), as 40% of participants lacked amyloid pathology. However, in amyloid biomarker-positive mild AD patients, buntanetap demonstrated nominally statistically significant dose-dependent cognitive benefits, supported by biomarker evidence of target and pathway engagement. Further evaluation of buntanetap in this patient population are warranted. A Phase 3 trial is currently underway to confirm these findings (NCT06709014).
Fang et al. (Mon,) studied this question.