Which non-amyloid mechanisms (tau, inflammation, metabolism) received FDA-authorized Alzheimer’s treatments 2020–2025?
Executive summary
From 2020 through 2025 the U.S. Food and Drug Administration authorised only anti‑amyloid disease‑modifying therapies for Alzheimer’s — notably lecanemab (Leqembi) and donanemab (Kisunla) — while no FDA approval is recorded in the provided sources for therapies whose primary mechanisms are tau‑targeting, anti‑inflammatory, or metabolic (not found in current reporting) [1] [2] [3]. Multiple tau, inflammation and metabolism programs received expedited FDA designations or entered late‑stage trials during 2024–2025, but those are development milestones, not approvals [4] [5] [6] [7].
1. FDA approvals 2020–2025: amyloid only — the record
The recent U.S. approvals that reshaped Alzheimer’s care through 2023–2024 are anti‑amyloid monoclonal antibodies: lecanemab received traditional approval in July 2023 and donanemab followed as an FDA‑authorised therapy; consensus reviews and fact sheets describe these as agents that remove beta‑amyloid and slow decline in early disease [1] [2] [3]. Reviews and pipeline summaries consistently report that the FDA’s approvals in this period were for anti‑Aβ immunotherapies, not for tau, inflammation, or metabolic‑mechanism drugs [1] [8] [2].
2. What the sources say about tau, inflammation and metabolism — active pipeline, not approvals
By contrast, the literature and industry notices in 2024–2025 show robust development activity across non‑amyloid targets: a surge of tau programs (antibodies, antisense oligonucleotides), inflammation‑directed agents and metabolism/bioenergetics candidates are in Phase 2/3 trials or have received expedited pathways from FDA [7] [9] [10]. Examples include FDA Fast Track designations for tau‑directed candidates such as Biogen’s BIIB080 and J&J’s posdinemab — these are regulatory accelerations, not marketing approvals [4] [5] [6].
3. Why designations aren’t the same as approvals — regulatory clarity
Fast Track, Acceptances of NDAs, and other designations shorten review timelines and facilitate communication between sponsor and FDA; they do not equal authorisation for clinical use. The sources explicitly report Fast Track status and trial progression for several tau agents (BIIB080, posdinemab) and acceptance of tau imaging NDAs (MK‑6240), while noting that no tau‑directed therapeutic had been approved as of the cited reviews [4] [5] [11] [12].
4. Evidence and dissent: amyloid approvals remain controversial
The anti‑amyloid approvals themselves sparked debate in the literature and press: critics point to limited clinical benefit relative to biological amyloid clearance and safety risks like ARIA (amyloid‑related imaging abnormalities), and major reviews stress cautious use and continued research into non‑amyloid pathways [1] [8] [13]. Agencies and research funders are explicitly supporting trials that combine anti‑amyloid drugs with tau‑ or inflammation‑targeting candidates to test multi‑target strategies [14] [7].
5. Pipeline numbers and priorities: how much of the work targets non‑amyloid mechanisms
Pipeline surveys show growing diversification: as of early 2025, hundreds of AD trials included many agents targeting inflammation (about 17% of agents), tau (~11%), and metabolism (~6%) among disease‑modifying programs — indicating priorities and resources but not approvals [9] [7]. The scientific literature repeatedly underscores that these mechanisms are active areas of development and that combination approaches are widely considered necessary [7] [15].
6. What’s missing from available reporting — limits of the record
Available sources do not mention any FDA approval between 2020 and 2025 that was granted primarily for a tau‑targeting, anti‑inflammatory, or metabolic mechanism therapy; they instead document approvals for anti‑amyloid antibodies and numerous non‑amyloid candidates in trials or with regulatory designations [1] [2] [4] [5]. Sources do not provide final approval dates or marketing authorisations for any tau, inflammation, or metabolism drugs in this timeframe [12] [11] [9].
7. Bottom line for clinicians, patients and policy‑makers
Through 2025, the FDA’s authorised disease‑modifying Alzheimer’s drugs were anti‑amyloid therapies; non‑amyloid mechanisms produced fast‑track designations, imaging tool NDAs and late‑stage trials but no FDA approvals in the provided materials. Stakeholders should treat designations and promising preclinical/clinical signals as important progress, not as substitutes for demonstrated safety and efficacy that regulatory approval requires [1] [6] [7].