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Pegozafermin

Written by The Peptide Record editorialClinical review not yet completedLast reviewed 15 September 2026Funding No ads, no affiliate links, no vendor payment

Pegozafermin is a real, Phase 3 FGF21 analog for MASH and severe high triglycerides — not approved anywhere, but real enough for Roche to pay up to $3.5 billion for the company developing it, in a deal that closed in October 2025. Unlike several other investigational drugs covered on this site, its Phase 2b trial cleanly met both of its pre-specified primary endpoints, and it has held FDA Breakthrough Therapy designation since 2023.

On this page
  1. What it is, and the mechanism
  2. The Phase 2b ENLIVEN trial
  3. Phase 3, Breakthrough Therapy, and the Roche acquisition
  4. What's not yet resolved

In brief

Should you care? Yes if you're comparing FGF21-class liver drugs against each other — pegozafermin is the one of this site's three with the cleanest primary-endpoint result and the earliest FDA Breakthrough Therapy designation, which matters when weighing which of these programs carries the least regulatory uncertainty today.

The short version

  • Pegozafermin is a glycoPEGylated FGF21 analog originally developed by 89bio, and now a Roche asset.
  • Its Phase 2b ENLIVEN trial met both primary histology endpoints at 24 weeks — fibrosis improvement (up to 27% vs. 7% on placebo) and MASH resolution (up to 26% vs. 2% on placebo).
  • FDA Breakthrough Therapy designation since September 2023; Phase 3 ENLIGHTEN trials are ongoing, with topline histology data not expected before 2027.
  • Roche acquired 89bio for up to $3.5 billion, a deal that closed 30 October 2025.

What it is, and the mechanism

Pegozafermin is a glycoPEGylated analog of fibroblast growth factor 21 (FGF21), engineered by 89bio for an extended half-life. Like efruxifermin and efimosfermin alfa, also covered on this site, it targets liver fat, inflammation and fibrosis directly rather than working through appetite suppression, and is being developed both for metabolic dysfunction-associated steatohepatitis (MASH) and for severe hypertriglyceridemia (SHTG) — a second, narrower indication neither of the other two FGF21 analogs on this site is currently pursuing.

The Phase 2b ENLIVEN trial

ENLIVEN, a 24-week randomized, double-blind, placebo-controlled Phase 2b trial in 219 adults with biopsy-confirmed F2/F3 NASH (192 with confirmed fibrosis), tested pegozafermin at 44mg every two weeks and 30mg weekly against placebo (Loomba R, Sanyal AJ, Kowdley KV, Bhatt DL, Alkhouri N, Frias JP, Bedossa P, Harrison SA, Lazas D, Barish R, Gottwald MD, Feng S, Agollah GD, Hartsfield CL, Mansbach H, Margalit M, Abdelmalek MF, N Engl J Med 2023;389(11):998-1008, DOI 10.1056/NEJMoa2304286, PMID 37356033). Both doses met the trial's two co-primary histology endpoints: fibrosis improvement of at least one stage without worsening of NASH (27% and 26% of patients, respectively, versus 7% on placebo) and NASH resolution without worsening of fibrosis (26% and 23%, versus 2% on placebo).

Phase 3, Breakthrough Therapy, and the Roche acquisition

The FDA granted pegozafermin Breakthrough Therapy designation for MASH with fibrosis on 21 September 2023, based on the ENLIVEN data above. 89bio subsequently launched the Phase 3 ENLIGHTEN program — ENLIGHTEN-Fibrosis (non-cirrhotic F2/F3 MASH) and ENLIGHTEN-Cirrhosis (compensated F4 cirrhosis) — both still enrolling as of this review, with topline histology data anticipated in the first half of 2027 for ENLIGHTEN-Fibrosis and 2028 for ENLIGHTEN-Cirrhosis. On 18 September 2025, Roche announced a definitive agreement to acquire 89bio for $14.50 per share in cash (about $2.4 billion) plus a non-tradeable contingent value right of up to $6 per share tied to approval and sales milestones (up to roughly $3.5 billion in total); the tender offer closed and 89bio became a wholly owned Roche subsidiary on 30 October 2025.

Three separate FGF21 analogs, three separate multibillion-dollar acquisitions by three different large pharmaceutical companies (Novo Nordisk, Roche, and GSK — see the other two pages linked below) all closed within a roughly nine-month span in 2025. That concentration of capital is itself a real, checkable fact worth knowing before treating any single FGF21 analog's prospects in isolation.

What's not yet resolved

Pegozafermin is not approved anywhere, and its Phase 3 program is the least mature of the FGF21 trio covered on this site by expected data timing — full histology results aren't expected until 2027 at the earliest. The ENLIVEN result above is real and peer-reviewed, but it is a 24-week Phase 2b readout in a smaller population than the ongoing Phase 3 trials; anyone relying on this page for current regulatory status should check Roche's own disclosures directly, since program ownership only recently transferred.

References

  1. Loomba R, Sanyal AJ, Kowdley KV, Bhatt DL, Alkhouri N, Frias JP, Bedossa P, Harrison SA, Lazas D, Barish R, Gottwald MD, Feng S, Agollah GD, Hartsfield CL, Mansbach H, Margalit M, Abdelmalek MF, "Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH," N Engl J Med 2023;389(11):998-1008, DOI 10.1056/NEJMoa2304286, PMID 37356033 (ENLIVEN).
  2. US FDA Breakthrough Therapy designation for pegozafermin, announced by 89bio, 21 September 2023 — company-reported.
  3. 89bio, Inc., press releases announcing initiation of the Phase 3 ENLIGHTEN-Fibrosis and ENLIGHTEN-Cirrhosis trials — company-reported.
  4. Roche, "Roche enters into a definitive merger agreement to acquire 89bio," media release, 18 September 2025; Roche, "Roche purchases shares in tender offer for 89bio, Inc.," 30 October 2025 — both roche.com, corroborated by contemporaneous reporting in STAT News, BioPharma Dive and Fierce Biotech.