Pemvidutide
Pemvidutide — the liver-first, muscle-sparing glucagon/GLP-1 dual: the MASH strategy and the biotech story

Class: peptide
Synonyms: Pemvidutide
ALT-801 (Altimmune development code)
a GLP-1/glucagon (GCG) dual receptor agonist ("balanced 1:1"). INCI: none
Function tags: MASH / fatty-liver (lead)
weight management / obesity
muscle-sparing weight loss
alcohol use disorder / alcohol liver disease
cardiometabolic (triglycerides, LDL, BP)
Overall evidence grade: B
WADA prohibited: no
Last updated: 2026-07-13

In brief: Pemvidutide (Altimmune's ALT-801) is a once-weekly, balanced 1:1 glucagon/GLP-1 dual agonist — and it closes the register's glucagon-dual cluster with a distinctive liver-first identity. Where most obesity drugs lead with GLP-1, pemvidutide leans on glucagon's direct liver effects (cutting liver fat, inflammation, fibrosis) to target MASH, with weight loss as the GLP-1-driven partner effect — earning FDA Breakthrough Therapy status for MASH. Its most compelling data is body composition: in the MOMENTUM Phase 2, ~15.6% weight loss was ~78% fat, only ~22% lean mass — class-leading muscle preservation that speaks directly to the GLP-1 era's muscle-loss worry. But it's also a small-biotech-vs-giants story with real volatility: its MASH trial showed MASH resolution and fibrosis improvement, yet an earlier primary-endpoint miss and analyst verdicts of "non-differentiating" weight loss hit the stock. The honest read: a mechanistically differentiated, muscle-sparing, liver-focused dual with Breakthrough status and a Phase 3 ahead — genuinely distinctive, but facing hard questions about whether its magnitude stands out in a crowded field. Its differentiation is strategy (liver + muscle), not headline weight number.

## Identity a **synthetic, once-weekly, peptide GLP-1/glucagon dual-receptor agonist** with a deliberately **balanced 1:1** activity ratio, from **Altimmune** (a small clinical-stage biotech). Unlike weight-first incretins, it's designed **liver-first** — its lead indication is **MASH** (metabolic dysfunction-associated steatohepatitis, the serious form of fatty-liver disease) — with obesity, **alcohol use disorder (AUD)** and **alcohol-associated liver disease (ALD)** also in development. ## Mechanism (as proposed) pemvidutide co-activates **two receptors in a balanced 1:1 ratio**. The **GLP-1 receptor** drives the familiar incretin effects — **appetite suppression, satiety, weight loss.** The **glucagon receptor** adds what GLP-1-only drugs lack: **direct hepatic actions** that **increase energy expenditure/fat oxidation** and **reduce liver fat, inflammation, and fibrosis** — the basis of the MASH strategy — while also helping **preserve lean mass** (a metabolic consequence of the glucagon arm). The deliberate **1:1 balance** distinguishes it from GLP-1-dominant duals; the trade-off with glucagon agonism is careful attention to glucose and heart-rate effects, managed by the balanced design and dosing. In short: **GLP-1 for weight/appetite, glucagon for liver and muscle-sparing** — a mechanism tuned for **MASH-plus-obesity** rather than weight alone.

Evidence grades by outcome:
outcome: MASH (the lead indication)
grade: C
base: IMPACT Phase 2b (48 wk): significant MASH resolution + fibrosis improvement; FDA Breakthrough
caveat: Real signal + regulatory validation — but an earlier 24-wk primary-endpoint miss; Phase 3 (PERFORMA) pending
outcome: Weight loss / obesity
grade: B
base: MOMENTUM Phase 2 (48 wk): ~15.6% vs 0.4% placebo
caveat: Solid — but mid-pack for the class (< survodutide's ~18.7%; ≈ mazdutide); analysts called it "non-differentiating"
outcome: Lean-mass preservation (the standout)
grade: B
base: Body composition: ~78% fat / ~22% lean of weight lost
caveat: Class-leading muscle sparing — arguably its best differentiator, addressing a real GLP-1-era concern
outcome: Cardiometabolic (lipids, BP, liver fat)
grade: B
base: Phase 2: ↓ triglycerides, LDL, liver fat, blood pressure
caveat: Consistent secondary benefits (glucagon + weight effects)
outcome: AUD / alcohol liver disease
base: RECLAIM (AUD) / RESTORE (ALD) trials ongoing; data 2026
caveat: Exploratory; readouts pending
outcome: Safety
grade: B
base: Phase 2/2b exposure
caveat: Favorable tolerability reported; investigational — Phase 3/long-term pending

Legal status:
region: EU
status: Not approved
note: investigational; not approved. Phase 2/2b complete; Phase 3 (PERFORMA, MASH) planned H2 2026. FDA Fast Track + Breakthrough (MASH) — advanced, well-validated program, but not yet approved.

Cosmetic claims:

Note: The liver-first glucagon dual that fights the muscle-loss problem — and the small biotech betting on differentiation. Pemvidutide (Altimmune) closes the register's GLP-1/glucagon dual cluster with a distinctive strategy and a strong story. Three threads: (1) it's a balanced 1:1 glucagon/GLP-1 agonist designed liver-first — for MASH (fatty-liver disease), not just weight; (2) its standout data is class-leading lean-mass preservation — ~78% of weight lost was fat, directly answering the GLP-1 era's big worry about muscle loss; (3) it's a small-biotech-vs-giants story with real market drama — impressive mechanism and FDA Breakthrough status, but mid-stage results that analysts called "non-differentiating," sending the stock down. Heading to Phase 3.
Status note: PERFORMA Phase 3 MASH H2 2026, end-of-Phase-2 FDA meeting, and AUD/ALD readouts are the catalysts — and the test of whether liver/muscle differentiation beats raw-magnitude competition

Sources:
Altimmune press releases: MOMENTUM Phase 2 obesity (ADA 2024) — 15.6% weight loss, 78.1% fat / 21.9% lean ("class-leading lean-mass preservation"); IMPACT Phase 2b MASH 48-week data (Dec 2025; EASL 2026) — MASH resolution + fibrosis improvement; PERFORMA Phase 3 planned H2 2026.
Pemvidutide mechanism: balanced 1:1 glucagon/GLP-1; glucagon → hepatic fat/inflammation/fibrosis; FDA Fast Track (MASH, AUD) + Breakthrough (MASH); RECLAIM (AUD)/RESTORE (ALD) trials.
FierceBiotech (June 2025): 24-wk primary-endpoint miss; William Blair "underwhelming"/"non-differentiating"; stock decline.
Class context: Springer 2025 review (survodutide ~18.7%, mazdutide ~14.8%, pemvidutide Phase 2). (Investigational; not approved as of 2026.)