Fosgonimeton (ATH-1017)
Fosgonimeton (ATH-1017) — the HGF/MET Alzheimer's drug that failed: the debunk and the data-fraud backstory

Class: small_molecule
Synonyms: Fosgonimeton
ATH-1017
NDX-1017 (earlier code)
Function tags: neurodegeneration (Alzheimer's — failed)
HGF/MET modulation
neuroprotection (hypothesized)
cognition (unproven)
Overall evidence grade: B
WADA prohibited: no
Last updated: 2026-07-13

In brief: Fosgonimeton (ATH-1017) is a small-molecule positive modulator of the HGF/MET system — the growth-factor pathway that's reduced in the Alzheimer's brain — developed by Athira Pharma as a once-daily injection for Alzheimer's. It matters to this register because it completes the story begun at Dihexa (#44): both target the same HGF/c-Met "brain growth factor" axis, but where Dihexa collapsed under retracted, fabricated data, fosgonimeton was taken all the way to a pivotal Phase 2/3 trial (LIFT-AD) — and honestly failed, missing its primary and key secondary endpoints (cognition and function no better than placebo). That's the rigorous debunk of the "enhance growth-factor signaling to treat neurodegeneration" hypothesis. The drama runs deeper: Athira's founding science was already tainted by a data-manipulation scandal (its CEO ousted over altered images) and an activist proxy fight, and after the failure the company clung to post-hoc subgroups while executives spun the miss as "encouraging." The honest read: a safe, well-tolerated drug for a compelling-sounding mechanism that, tested properly, did not help Alzheimer's patients — a clinical debunk wrapped in a research-integrity cautionary tale. Safety wasn't the problem; efficacy was.

## Identity a **synthetic small molecule** designed to **enhance signaling through the HGF/MET (c-Met) system** — the hepatocyte-growth-factor pathway that promotes neuronal survival and synaptic function, and which is **diminished in the Alzheimer's hippocampus.** Given as a **once-daily subcutaneous injection**, it was Athira Pharma's lead candidate for **Alzheimer's disease** (and tested in Parkinson's/Lewy-body dementia). It is the **clinically-developed cousin** of Dihexa (#44), which targets the same HGF/c-Met axis. ## Mechanism (as proposed) **HGF (hepatocyte growth factor)** and its receptor **MET (c-Met)** form a signaling system that supports **neuronal survival, synaptic function, and repair**; **MET expression is reduced in the Alzheimer's hippocampus**, which motivated the idea that **positively modulating HGF/MET** could be **neuroprotective and disease-modifying.** Fosgonimeton was designed to **enhance this signaling** (improving synaptic function and protecting neurons). The mechanism is **biologically reasonable and shares its target with Dihexa (#44)** — but LIFT-AD is the decisive data point: **enhancing HGF/MET signaling, at the tested dose and duration, did not slow cognitive or functional decline** in mild-to-moderate Alzheimer's. It's a textbook reminder that **a plausible, well-supported mechanism is a hypothesis, not a result** — and that the **only way to know is an adequately powered trial**, which here returned a clear negative.

Evidence grades by outcome:
outcome: Alzheimer's disease (the lead use)
grade: F
base: Phase 2/3 LIFT-AD: missed primary (GST) + key secondaries; ACT-AD Ph2 missed; earlier failures
caveat: Tested and failed at pivotal scale — cognition/function no better than placebo (P≈0.70). Not "untested" — clearly negative
outcome: Parkinson's / Lewy-body dementia
grade: F
base: SHAPE cut 75→28 patients, missed primary; "5-patient subgroup"
caveat: Underpowered, failed; subgroup grasping
outcome: Subgroup "signals" (APOE4, monotherapy, advanced disease)
grade: D
base: Post-hoc / prespecified subgroups after failed primaries
caveat: Classic post-hoc rescue; hypothesis-generating at best, not evidence of efficacy
outcome: HGF/MET mechanism (as biology)
grade: C
base: Real: MET signaling diminished in AD hippocampus; neuroprotective in models
caveat: The biology is legitimate; it didn't translate to clinical benefit — the whole point
outcome: Safety
grade: B
base: Phase 1–3 exposure
caveat: Consistently safe and well-tolerated — its failure was efficacy, not safety

Legal status:
region: US
status: Not approved
note: not approved for any indication; its lead Alzheimer's program failed Phase 2/3 (2024). Investigational; the pathway continues only in a separate ALS candidate (ATH-1105).

Cosmetic claims:

Note: The rigorous clinical debunk of the "boost brain growth factors" idea — with a data-fraud scandal attached. Fosgonimeton finishes a story the register started at Dihexa (#44): it targets the same HGF/c-Met pathway, but unlike Dihexa (retracted for fabrication), it was actually taken to Phase 2/3 in Alzheimer's — and failed honestly. Two big stories: (1) the scientific debunk — the hypothesis that "positively modulating HGF/growth-factor signaling treats neurodegeneration" was tested rigorously and did not beat placebo; (2) the corporate drama — Athira's program was already shadowed by a data-manipulation scandal (its CEO ousted over altered images) and an activist proxy fight before the pivotal trial flopped. It's a small molecule, not a peptide.
Status note: Alzheimer's program failed/effectively discontinued; the HGF/MET pathway continues only via oral ATH-1105 in ALS — the remaining test of whether the mechanism helps any neurodegenerative disease

Sources:
LIFT-AD Phase 2/3 (NCT04488419) topline, Sept 2024: missed primary (GST combining ADAS-Cog11 + ADCS-ADL23) and key secondaries; GST ≈ −0.08, P ≈ 0.70; APOE4 subgroup signal (CTAD 2024).
ACT-AD Phase 2 (NCT04491006) — missed primary, monotherapy P300 hint; SHAPE (NCT04831281, PDD/DLB) — enrollment cut 75→28, missed.
Hua X, et al. Safety, Tolerability, PK/PD of the HGF/MET Positive Modulator Fosgonimeton… J Alzheimers Dis. 2022;86(3):1399-1413 (Phase 1); ALZFORUM fosgonimeton entry (MET reduced in AD hippocampus; pivot to ATH-1105 for ALS).
STAT News (Sept 2024): trial failure "marred by a data manipulation scandal" (CEO altered images, ousted); FierceBiotech: activist proxy fight, post-hoc subgroup reliance. (Not approved; Alzheimer's program failed as of 2026.)