Phase 1 data for sabirnetug (ACU193) showed a favorable safety profile with low overall rates of ARIA-E and evidence of target engagement, including plaque reduction at the highest doses. In Phase 2, participants entering the open-label extension (OLE) will receive 35 mg/kg intravenously every four weeks for 52 weeks. ALTITUDE-AD has enrolled 542 people with early Alzheimer’s disease across the United States, Canada, the European Union, and the United Kingdom, with topline results from the placebo-controlled portion expected in late 2026.
The core development is operational: Acumen has dosed the first participant in the OLE of its Phase 2 ALTITUDE-AD trial. The extension offers all completers of the 18‑month placebo-controlled study continuous access to sabirnetug under the same clinical and safety assessments. The OLE converts a blinded, comparative protocol into a year of real-world-like exposure within the trial infrastructure, creating a longer safety and biomarker runway while preserving continuity at sites.
Strategically, opening the OLE now is designed to lock in participant retention, build long-duration safety coverage, and prepare a differentiation case around an oligomer-selective antibody in a class defined to date by plaque-binding agents. The cadence of monthly infusions aligns with donanemab-style operational rhythms while potentially offering a safety or MRI burden advantage if the low ARIA-E signal from Phase 1 persists. For a mid-cap sponsor without a marketed Alzheimer’s franchise, an OLE also functions as a hedge: it enables dose optimization, ARIA management refinements, and exploratory biomarker-cognition modeling ahead of a pivotal decision, while de-risking the transition to a planned subcutaneous formulation leveraging ENHANZE technology and longer-term ambitions around enhanced brain delivery.
For sites, the OLE stabilizes infusion volumes through 2027, reduces churn from placebo exits, and sustains trained teams familiar with ARIA workflows and cognitive/functional assessments. However, the monthly 35 mg/kg dosing will continue to draw on MRI capacity and central imaging coordination, keeping pressure on scheduling and read timelines. CROs and imaging vendors benefit from predictable volume and extended longitudinal datasets but will need to manage expectation bias inherent in open-label follow-up, particularly for patient-reported and functional outcomes. Regulators gain a richer safety narrative and biomarker trajectory across two years of exposure, yet the bar remains unchanged: slowing of cognitive and functional decline versus placebo in the blinded Phase 2 will drive credibility, not plaque kinetics alone. Payers and policymakers, still calibrating coverage parameters across the anti-amyloid class, will scrutinize ARIA rates, discontinuation patterns, MRI intensity, and any operational tailwinds a monthly schedule or SC conversion could offer.
The next inflection is the late-2026 Phase 2 readout. Signals to watch include ARIA-E incidence and management requirements relative to class benchmarks, consistency between biomarker movement and clinical endpoints, and subgroup performance in a heterogeneous early-AD population. Operationally, clarity on infusion discontinuation criteria, MRI frequency during maintenance, and the feasibility of switching to subcutaneous delivery will influence both pivotal trial design and eventual site adoption. The unresolved questions are whether oligomer selectivity translates into a clinically and operationally material advantage, whether monthly dosing can sustain adherence without overburdening imaging resources, and how quickly Acumen can scale manufacturing and distribution if it advances. If the Phase 2 efficacy is credible and safety remains manageable, expect a pivotal program that bakes in OLE learnings, explores SC administration, and tests a more pragmatic monitoring schedule—pressure-tested against a class moving toward streamlined protocols and post-market real-world data commitments.
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.
