Pemvidutide Improves Multiple MASH Fibrosis Markers at 48 Weeks

Investigational pemvidutide significantly increased the proportion of patients with metabolic dysfunction-associated steatohepatitis (MASH) who achieved concurrent responses across multiple noninvasive tests (NITs) of liver fat, inflammation, and fibrosis at 48 weeks compared with placebo, according to responder analyses of the phase 2b IMPACT trial presented at The Liver Meeting 2026 in Denver, Colorado.¹

In the most stringent composite analysis, which required concurrent improvements in liver fat content (LFC), enhanced liver fibrosis (ELF) score, and liver stiffness measurement (LSM), 25.8% of patients receiving pemvidutide 1.8 mg responded vs none receiving placebo (P < .0001).¹

Pemvidutide is a once-weekly, balanced 1:1 glucagon/glucagon-like peptide-1 (GLP-1) dual receptor agonist in development for MASH.¹ IMPACT (NCT05989711) randomly assigned 212 adults with biopsy-confirmed MASH and F2 or F3 fibrosis in a 1:2:2 ratio to subcutaneous pemvidutide 1.2 mg, pemvidutide 1.8 mg, or placebo, without dose titration.¹,²

At 24 weeks, MASH resolution without worsening of fibrosis occurred in 59.1% of patients receiving 1.2 mg and 52.1% receiving 1.8 mg vs 19.1% receiving placebo (P < .0001 for both). Fibrosis improvement without worsening of MASH occurred in 31.8% and 34.5% vs 25.9%, respectively, a difference that did not reach statistical significance. Mean weight loss was 5.0% and 6.2% with pemvidutide vs 1.0% with placebo (P < .001 for both).²

“The combination of MASH resolution and weight loss achieved at only 24 weeks is unique,” Mazen Noureddin, MD, MHSc, of Houston Methodist Hospital, said in a statement at the time.²

The US Food and Drug Administration (FDA) granted pemvidutide breakthrough therapy designation for MASH in January 2026.³ To date, 2 therapies have received FDA accelerated approval for MASH with moderate to advanced fibrosis: resmetirom (Rezdiffra) in March 2024 and semaglutide in August 2025.⁴

Why Use Composite Noninvasive Test Responses?

Each NIT threshold used in the analysis has been linked to histologic benefit. According to the investigators, a reduction in LFC of at least 30% is associated with MASH improvement, and a reduction in alanine aminotransferase (ALT) of at least 17 U/L is predictive of histologic response. Reductions of at least 0.5 in ELF score or at least 30% in LSM are associated with fibrosis regression.¹

Although individual NITs may indicate therapeutic effect, the investigators noted that combining multiple overlapping tests may provide a more rigorous assessment by increasing diagnostic accuracy and stringency. LFC, ELF score, LSM, and ALT were secondary endpoints in IMPACT.¹

How Did Pemvidutide Perform in the 48-Week Responder Analyses?

At baseline, patients had a mean age of 53 years and a mean body mass index of 39 kg/m². Overall, 58% were female and 43% had type 2 diabetes.¹

A greater proportion of patients receiving pemvidutide achieved a concurrent MASH improvement response, defined as a reduction of at least 30% in LFC, at least 17 U/L in ALT, and at least 30% in LSM:¹

• 1.2 mg: 34.3% (P = .0001)
• 1.8 mg: 42.9% (P < .0001)
• Placebo: 3.3%

Concurrent responses in 2 markers of fibrosis improvement, an ELF reduction of at least 0.5 and an LSM reduction of at least 30%, also favored pemvidutide:¹

• 1.2 mg: 27.8% (P = .0003)
• 1.8 mg: 32.4% (P < .0001)
• Placebo: 3.2%

In the most stringent analysis, which required an LFC reduction of at least 50% alongside the ELF and LSM thresholds, response rates were:¹

• 1.2 mg: 17.1% (P = .0018)
• 1.8 mg: 25.8% (P < .0001)
• Placebo: 0.0%

The responder analyses build on 48-week topline results Altimmune reported in December 2025, which showed continued improvement in ELF and LSM from week 24 with both doses.⁵ In earlier reporting, discontinuations due to adverse events occurred in 0% of patients receiving 1.2 mg, 1.2% receiving 1.8 mg, and 3.5% receiving placebo, with no serious or severe treatment-related adverse events.³

What Comes Next for Pemvidutide?

The analyses rely on NITs rather than 48-week liver biopsy, and the abstract did not report the number of patients with evaluable data for each composite endpoint or safety data through 48 weeks. Composite NIT responses have not been validated as surrogate endpoints for regulatory approval.

In August 2026, Altimmune began enrolling the phase 3 PERFORMA trial in adults with MASH and F2 or F3 fibrosis. The event-driven trial plans to enroll approximately 990 patients in a biopsy-based cohort, with a primary endpoint of MASH resolution and/or fibrosis improvement at 52 weeks, and approximately 800 patients in a second cohort with fibrosis identified by NITs. Patients will titrate from 1.2 mg to a trial dose of 1.8 mg or 2.4 mg. A 52-week readout is expected in 2029, and final approval would be based on liver-related events at approximately 60 months.⁶

References:

1. Alkhouri N, Noureddin M, Tomah S, et al. Pemvidutide treatment results in concurrent reductions in multiple noninvasive tests for hepatic inflammation and fibrosis: 48-week responder analyses of the IMPACT phase 2b trial in metabolic dysfunction-associated steatohepatitis. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.
2. Brooks A. Pemvidutide shows significant MASH effects, weight loss at 24 weeks in phase 2b IMPACT trial. HCPLive. Published June 26, 2025. Accessed November 8, 2026. https://www.hcplive.com/view/pemvidutide-shows-significant-mash-effects-weight-loss-24-weeks-phase-2b-impact-trial
3. Johnson V. Pemvidutide gets breakthrough therapy designation for MASH. HCPLive. Published January 5, 2026. Accessed November 8, 2026. https://www.hcplive.com/view/pemvidutide-gets-breakthrough-therapy-designation-for-mash
4. FDA approves semaglutide for MASH with fibrosis. AJMC. Published August 18, 2025. Accessed November 8, 2026. https://www.ajmc.com/view/fda-approves-semaglutide-for-mash-with-fibrosis
5. Altimmune reports positive 48-week phase 2b data for pemvidutide in MASH. Nasdaq. Published December 19, 2025. Accessed November 8, 2026. https://www.nasdaq.com/articles/altimmune-reports-positive-48-week-phase-2b-data-pemvidutide-mash
6. Altimmune. Altimmune initiates PERFORMA phase 3 trial of pemvidutide in patients with MASH. BioSpace. Published August 3, 2026. Accessed November 8, 2026. https://www.biospace.com/press-releases/altimmune-initiates-performa-phase-3-trial-of-pemvidutide-in-patients-with-mash