At the recently held AD/PD 2025 International Conference on Alzheimer’s and Parkinson’s Diseases (PD), Annovis Bio reported buntanetap’s potential to improve both motor and cognitive functions in early-stage PD patients with mild dementia. This underscores the growing need for effective dementia treatments in PD, noting the drug’s promising sub-group outcomes as a critical step in addressing this significant unmet medical need, says GlobalData.
Reportedly, buntanetap failed to reach the primary endpoint in the total intention-to-treat (ITT) population. But, showed potential at improving motor and non-motor functions in patients with early PD and mild dementia.
Following sub-group analysis of early PD patients with mild dementia, as measured by a Mini Mental State Examination (MMSE) of 20-26, cognitive decline was prevented in patients who received 20mg of buntanetap for six months. In addition, buntanetap demonstrated improvements in MDS-UPDRS Parts I, II, III, and IV, Clinical Global Impression of Severity (CGIS), Wechsler Adult Intelligence Scale fourth edition (WAIS-IV), and Participant Global Impression of Change (PGIC) clinical endpoints, meeting all primary and secondary endpoints in this sub-group. As such, improvements in both cognition and motor function signal a promising therapy for patients with early PD with mild dementia.
Christie Wong, Managing Neurology Analyst at GlobalData, comments, “The key opinion leaders (KOLs) previously interviewed by GlobalData overwhelmingly cited dementia as the most difficult-to-treat non-motor symptom of PD. The development of more effective therapies for dementia is a major unmet need in PD, as the current therapies provide only modest benefit. KOLs stated that dementia is a common problem in PD patients that further affects medication compliance and remains difficult to treat.”
However, drug development for this indication has historically been challenging. For example, IRLAB Therapeutics recently announced that while the Montreal Cognitive Assessment (MoCA) indicated an improvement in cognitive impairment for patients treated with 600mg of pirepemat, it did not reach statistical significance in a Phase IIb study (REACT-PD [NCT05258071]).
Moving forward, Annovis Bio plans to explore biomarkers to differentiate patients with PD from patients without PD, as well as understanding the differences between PD patients with cognitive impairment and patients with Alzheimer’s disease. In addition, the company has requested a Type C meeting with the FDA, with the intention to conduct a randomised, double-blind, placebo-controlled, multi-center Phase II/III study in patients with dementia with Lewy bodies and PD dementia.
Wong concludes, “In the late-stage pipeline, there are currently three assets that investigate cognitive function in PD patients; buntanetap is set to compete with Anavex’s blarcamesine and IRLAB Therapeutics’ pirepemat. Pipeline agents that address cognitive complications, including PD dementia, will likely see a high initial uptake following approval due to the limited availability of approved treatments for this indication and high unmet need.”
*7MM = The US, France, Germany, Italy, Spain, the UK, and Japan.