All 84 U.S. sites are active for Annovis Bio’s pivotal Phase 3 Alzheimer’s program, with the first participants reaching the 6‑month treatment milestone. The company reports the study is 25% complete and remains on pace for a 6‑month symptomatic readout in the second half of 2026.
The Phase 3 trial (NCT06709014) targets 760 patients with early Alzheimer’s and biomarker‑confirmed amyloid pathology. The design splits readouts: an initial 6‑month symptomatic assessment, followed by an 18‑month analysis aimed at disease modification. Participants who complete the first 6 months remain on blinded therapy for an additional 12 months, consolidating data continuity across both endpoints. Activation of all U.S. sites signals the transition from start‑up to complete execution, with enrollment and treatment underway across the network.
Strategically, the dual‑readout structure looks like a hedge in a crowded Alzheimer’s landscape. A nearer‑term symptomatic signal provides a potential proof point and financing waypoint while the longer 18‑month window seeks the durability regulators now expect post‑lecanemab and donanemab. Keeping the study U.S.‑only simplifies oversight and reduces variability. Still, it also concentrates competition for amyloid‑positive, early‑stage patients amid ongoing commercial roll‑outs and rival trials tapping the same diagnostic pipeline. The cadence of site activation and early progression to the 6‑month mark suggests operational momentum. Still, the critical pressure point will be sustaining that velocity to 760 randomized patients without compromising cohort balance or endpoint integrity.
For sites, the protocol’s amyloid confirmation standard and two‑stage readout translate into front‑loaded screening complexity and long‑tail retention obligations. Imaging and lumbar puncture capacity remain limiting factors in many regions, and the 18‑month blinded continuation will strain caregiver engagement, visit adherence, and throughput for cognitive and functional assessments. CROs and central vendors will be measured on prescreen workflows, screen‑fail management, and the minimization of inter‑site variability in endpoints commonly scrutinized by regulators. The U.S. footprint may streamline monitoring and data flow. Still, it heightens exposure to localized staffing shortages, PET slot scarcity, and competition from standard‑of‑care infusions that can siphon patients and clinic time.
The next phase is about pace and quality. Watch for quarterly enrollment inflection, retention trends as more participants cross 6 months, and clarity on concomitant medication policies that could intersect with background anti‑amyloid use. The planned symptomatic analysis for 2H26 will need to demonstrate a consistent effect across predefined cognitive and functional measures to justify continued investment ahead of the 18‑month readout. If enrollment tightens, expansion beyond the U.S. or adoption of blood‑based biomarkers for prescreening could become necessary to hold timelines. The core risk remains execution: screen‑fail rates, retention drag, and endpoint variability can quickly erode the margin needed to translate operational progress into a regulatory‑credible signal.
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.
