Living dossier · Competitive landscape

FGF21 pathway in Metabolic dysfunction-associated steatohepatitis

Primary identifiers: 16
Sponsors tracked: 8
Evidence types: 2 of 3
Last refreshed: 2026-07-28 · monthly

MightyRayn panel synthesis

OmniRayn’s reading of this landscape — our interpretation, not a registry fact

The most expensive open question in liver disease. Two sponsors are running Phase 3 programmes here at a scale that rivals cardiovascular outcome trials — one with primary completion listed as 2033 — and a third has arrived with a one-time AAV gene therapy aimed at the same target the others dose weekly. Against that, the single most important datum on this page is a failure: in compensated cirrhosis the lead analogue MISSED its primary endpoint at week 36, with p-values of 0.62 and 0.52. The week-96 figure that circulates instead is a secondary outcome, measured after the primary had already failed and on a biopsy population that shrank from 154 patients to 134. A rival is now running a Phase 3 in that same cirrhotic population. The earlier-stage data are better but not clean either: the Phase 2b that justified Phase 3 was 92 percent white and 62 percent female at US sites only, and its higher dose lost significance under the full-analysis-set sensitivity check while the lower dose held. Note also that a large pharmaceutical company ran two Phase 2b studies of a PEGylated FGF21 here and did not proceed to Phase 3 — this target has been attempted before. A published network meta-analysis across 29 trials ranks this pathway's leading agent above the approved thyroid-hormone-receptor-beta agonist on both endpoints. Treat that carefully: it is an INDIRECT comparison, no head-to-head trial exists, and as our thyroid-hormone-receptor-beta landscape sets out, placebo response in this disease varies enough between studies to make cross-trial ranking unreliable. Same disease, two targets, and the honest position is that nobody yet knows which is better.

Programs and primary evidence

Sponsor	Asset	Phase	Mechanism	Primary source
GlaxoSmithKline	Efimosfermin alfa	3	long-acting FGF21 analogue	NCT07221227 — ZENITH-1 Phase 3 in biopsy-confirmed F2/F3-stage MASH
Akero Therapeutics	Efruxifermin	3	Fc-FGF21 fusion analogue	NCT06528314 — Phase 3 in subjects with compensated cirrhosis due to NASH/MASH
Akero Therapeutics	Efruxifermin (non-cirrhotic Phase 3)	3	bivalent Fc-FGF21 analogue	NCT06215716 — Phase 3 in non-cirrhotic MASH with fibrosis, n=1650 across 356 sites, primary completion listed as 2033 — a decade-long commitment
Akero Therapeutics	Efruxifermin (non-invasive diagnosis)	3	same analogue enrolled without mandatory biopsy	NCT06161571 — Phase 3 in NON-INVASIVELY diagnosed MASH/MASLD, n=700 — an attempt to move the field off biopsy-based entry criteria
Akero Therapeutics	Efruxifermin (HARMONY, Phase 2b)	2	Fc-FGF21 analogue in F2/F3 fibrosis	NCT04767529 — Phase 2b, n=128, the study that supported moving to Phase 3
Akero Therapeutics	Efruxifermin (SYMMETRY, cirrhosis)	2	same analogue in compensated cirrhosis, a harder population	NCT05039450 — Phase 2b in compensated cirrhosis due to MASH, n=213. Read the published report on this page before citing this programme — the primary endpoint was NOT met
Akero Therapeutics	Efruxifermin (BALANCED, Phase 2a)	2	first controlled test of the analogue in this disease	NCT03976401 — Phase 2a, n=110 — the origin study for the efruxifermin programme
89bio	Pegozafermin (ENLIGHTEN-Fibrosis)	3	glycoPEGylated FGF21 analogue	NCT06318169 — Phase 3 in MASH with fibrosis, n=1350 across 361 sites — the competing analogue at comparable scale
89bio	Pegozafermin (ENLIGHTEN-Cirrhosis)	3	same analogue in compensated cirrhosis	NCT06419374 — Phase 3 in compensated cirrhosis due to MASH, n=762 — entering the same population where the rival analogue's Phase 2b primary endpoint failed
89bio	Pegozafermin (ENLIVEN, Phase 2b)	2	analogue in biopsy-confirmed disease	NCT04929483 — Phase 2b in biopsy-confirmed MASH, n=222 — the study underpinning the pegozafermin Phase 3 programme
Bristol-Myers Squibb	BMS-986036 / pegbelfermin (stage 3 fibrosis)	2	PEGylated FGF21	NCT03486899 — Phase 2b in MASH with stage 3 fibrosis, n=197. CAVEAT: large-pharma programme completed in 2020 that did not progress to Phase 3 — the field's earlier attempt at this target
Bristol-Myers Squibb	BMS-986036 / pegbelfermin (cirrhosis)	2	same PEGylated FGF21 in compensated cirrhosis	NCT03486912 — Phase 2b in compensated cirrhosis, n=155, completed 2020 without a Phase 3 successor
Kriya Therapeutics	VV-14303 (AAV FGF21 gene therapy)	1/2	adeno-associated viral vector delivering FGF21 rather than dosing a protein	NCT07732400 — First-in-human dose escalation, n=56 — a one-time gene therapy attacking the same target the weekly injectables address, and the newest entry on this page
Houston Methodist Hospital	SYMMETRY report (NEJM)	—	Fc-FGF21 analogue in compensated cirrhosis	10.1056/NEJMoa2502242 — THE PRIMARY ENDPOINT WAS NOT MET: fibrosis reduction at week 36 occurred in 13% on placebo vs 18% (p=0.62) and 19% (p=0.52). The frequently-quoted week-96 result — 29% vs 11% on the 50mg dose — is a SECONDARY outcome measured after the primary had already failed, on a shrinking biopsy population (154 patients at week 36, 134 at week 96)
University of Oxford	HARMONY report (Lancet Gastro Hep)	—	Fc-FGF21 analogue in F2/F3 fibrosis	10.1016/S2468-1253(23)00272-8 — Fibrosis improvement in 39% and 41% vs 20% placebo at week 24. CARRY THE CAVEATS: the cohort was 92% white and 62% female, n=128 at 41 US clinics only, and in the full-analysis-set sensitivity check the 50mg arm LOST significance (p=0.123) while the 28mg arm held
Federal University of Rio de Janeiro	network meta-analysis (Hepatology)	—	indirect comparison across the whole treatment field	10.1097/HEP.0000000000001254 — Across 29 randomised trials and 9,324 patients, ranks pegozafermin highest for both fibrosis regression and disease resolution, ahead of resmetirom on both. CAVEAT: this is an INDIRECT ranking from a network meta-analysis, not a head-to-head trial — no study has compared these agents directly

Method and limits

Programs are enumerated from primary registries (ClinicalTrials.gov, PubMed). A program appears here only if a primary record links this target to this indication as a therapeutic hypothesis — associations and risk markers are excluded by design.
Every claim above carries the identifier it rests on. We report what the record states; we do not assert efficacy, and computational findings are pending wet-lab confirmation.
Absence is not evidence of absence: unregistered, non-US and stealth-stage programs are not visible to these sources.
This page refreshes monthly (no net-new primary entity in 27 days). Mechanism classifications are our reading of the public record and may be revised.

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