Annovis reported that in its Phase 3 study in early Parkinson’s disease (NCT05357989), buntanetap halted cognitive decline across the overall population, with patients exhibiting Alzheimer’s amyloid co-pathology—about 25% of the cohort—showing roughly a three-times greater cognitive response. The company also cited reductions in plasma pTau217, total tau, and brain-derived tau following treatment, aligning the clinical effect with biomarker changes commonly used in Alzheimer’s disease.
The core update is a post hoc analysis linking amyloid co-pathology to both faster baseline cognitive deterioration and a stronger treatment effect with buntanetap, which Annovis positions as a multi-protein therapeutic targeting toxic species implicated in both PD and AD. The data will be detailed at the CTAD meeting in early December, with the company framing the biomarker reductions as supportive evidence of disease-modifying activity. No specific effect sizes, scales, or statistical parameters were disclosed in the announcement, and motor outcomes were not addressed.
Strategically, Annovis is leaning into the biological overlap across neurodegenerative diseases to carve out a biomarker-enriched path within PD cognition—an area with limited therapeutic options and fragmented endpoints. The move tackles a persistent tension in PD development: heterogeneous cognitive trajectories that often dilute signal in all-comer trials. If the amyloid-positive subgroup is driving the observed benefit, enrichment could sharpen efficacy and simplify regulatory dialogue. The flip side is that these are retrospective findings; without pre-specified stratification and clear multiplicity control, the signal risks being viewed as exploratory. Anchoring a PD program to AD-derived plasma biomarkers also tests regulators’ willingness to accept cross-indication markers as supportive evidence outside Alzheimer’s.
The operational implications are immediate. Sponsors pursuing PD cognition will feel pressure to incorporate amyloid status—via plasma pTau217/BD-tau, PET, or CSF—into screening and stratification, raising costs and timelines but potentially improving trial power. Sites will need to stand up or expand blood biomarker workflows, negotiate budgets for central lab support, and coordinate across movement disorder and memory clinics to identify and manage co-pathology. CROs and central labs can expect demand for validated plasma assays, standardized cutoffs, and sample-handling protocols that hold up under regulatory scrutiny. For regulators, the package will need to link biomarker shifts to clinically meaningful cognitive endpoints in PD, not just show directional consistency with AD markers. Payers will look for clarity on the target population and durability of effect, particularly if enrichment narrows the eligible pool.
Near term, the CTAD presentation is the inflection point. Key reads include absolute cognitive effect sizes and scales used, statistical robustness of the subgroup analysis, assay methods and thresholds for pTau217 and BD-tau, and any safety and motor-function context that could influence risk-benefit in early PD. Longer term, watch whether Annovis formalizes an enrichment strategy around amyloid-positive PD or pivots toward Parkinson’s disease dementia, and whether it seeks alignment with FDA on biomarker-supported claims in PD cognition. The strategic bet is clear: trade a smaller, biomarker-defined market for a cleaner efficacy story. The risk is equally clear: if the signal attenuates with prospective stratification or fails to map onto accepted PD cognitive endpoints, the cross-disease biomarker narrative may not carry regulatory weight.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
