Annovis Bio has reported promising results from its Phase III clinical trial of buntanetap for early Parkinson's disease (PD) patients with mild dementia at the International Conference on Alzheimer's and Parkinson's Diseases (AD/PD 2025). The six-month, randomized, double-blind, placebo-controlled study evaluated 10mg and 20mg doses of buntanetap against placebo, revealing significant potential for addressing both motor and cognitive symptoms.
The trial data showed mixed results across different patient populations. While buntanetap failed to reach the primary endpoint in the total intention-to-treat population, showing no statistically significant change from baseline to Month 6 in the Movement Disorder Society-Sponsored Revision of the Unified PD Rating Scale (MDS-UPDRS) Part II score, it demonstrated statistically significant improvements across all primary and secondary endpoints in the per-protocol population.
Most notably, buntanetap showed promise in preventing cognitive decline. Mini Mental State Examination (MMSE) scores worsened in patients receiving placebo but remained stable in those receiving buntanetap. A subgroup analysis focusing on early PD patients with mild dementia (MMSE scores of 20-26) revealed that 20mg of buntanetap effectively prevented cognitive decline over the six-month treatment period.
Comprehensive Improvements in Multiple Domains
In the mild dementia subgroup, buntanetap demonstrated improvements across multiple clinical measures, including MDS-UPDRS Parts I, II, III, and IV, Clinical Global Impression of Severity, Wechsler Adult Intelligence Scale fourth edition, and Participant Global Impression of Change. The drug met all primary and secondary endpoints in this specific patient population, suggesting a dual benefit for both cognitive and motor functions.
"The ability to address both motor symptoms and cognitive decline represents a significant advancement for patients with early Parkinson's disease who also experience mild dementia," said a representative from Annovis Bio during the AD/PD 2025 'Advances in PD Treatment' presentation.
Addressing a Critical Unmet Need
Cognitive impairment, particularly dementia, represents one of the most challenging aspects of Parkinson's disease management. Key opinion leaders interviewed by GlobalData have consistently identified dementia as the most difficult-to-treat non-motor symptom of PD. Current therapies provide only modest benefits, and medication compliance is further complicated by cognitive decline.
The development landscape for cognitive treatments in PD has historically been challenging. Last month, IRLAB Therapeutics reported that their candidate pirepemat showed improvement in cognitive impairment as measured by the Montreal Cognitive Assessment, but failed to reach statistical significance in their Phase IIb REACT-PD study.
Future Development Plans
Annovis Bio has outlined several next steps for buntanetap's development program. The company plans to explore biomarkers that can differentiate PD patients from non-PD patients, as well as understand the differences between PD patients with cognitive impairment and those with Alzheimer's disease.
Additionally, Annovis has requested a Type C meeting with the U.S. Food and Drug Administration to discuss conducting a randomized, double-blind, placebo-controlled, multicenter Phase II/III study in patients with dementia with Lewy bodies and PD dementia.
Competitive Landscape
In the late-stage pipeline for cognitive function in PD, buntanetap will compete with Anavex's blarcamesine and IRLAB Therapeutics' pirepemat. Given the limited availability of approved treatments for cognitive complications in PD and the high unmet need, successful pipeline agents addressing PD dementia are expected to see high initial uptake following approval.
The potential for a dual-action therapy that addresses both motor symptoms and cognitive decline could position buntanetap as a valuable treatment option for the significant number of PD patients who develop dementia during their disease course.
