8-K: Altimmune's Pemvidutide Achieves Positive Topline Results in Phase 2b MASH Trial, Demonstrating Significant Resolution and Weight Loss

Altimmune, Inc. announced positive topline results from its IMPACT Phase 2b trial for pemvidutide in metabolic dysfunction-associated steatohepatitis (MASH), demonstrating significant MASH resolution and weight loss with favorable tolerability.

Summary

• The IMPACT Phase 2b trial enrolled 212 participants with biopsy-confirmed MASH and fibrosis stages F2/F3, with and without diabetes.
• MASH resolution without worsening of fibrosis was achieved in 59.1% of participants receiving pemvidutide 1.2 mg and 52.1% for 1.8 mg, compared to 19.1% for placebo (p<0.0001 for both doses).
• Fibrosis improvement without worsening of MASH was observed in 31.8% (1.2 mg) and 34.5% (1.8 mg) of participants, versus 25.9% for placebo; these differences were not statistically significant in the primary ITT analysis.
• A supplemental AI-based analysis demonstrated statistically significant reductions in fibrosis, with 30.6% of participants receiving pemvidutide 1.8 mg achieving a 60% or more reduction in fibrosis compared to 8.2% receiving placebo (p<0.001).
• Mean weight loss at 24 weeks was 5.0% for the 1.2 mg dose and 6.2% for the 1.8 mg dose, compared to 1.0% in the placebo arm (p<0.001 for both doses), with no plateauing observed.
• Liver fat reductions were 58.0% (1.2 mg) and 62.8% (1.8 mg) versus 16.2% in the placebo group (p<0.001 for both doses).
• Pemvidutide demonstrated favorable safety and tolerability, with adverse event (AE) related discontinuations of 0.0% (1.2 mg) and 1.2% (1.8 mg) versus 2.4% in the placebo group.
• No serious adverse events (SAEs) related to study medication or arrhythmias were reported at 24 weeks.
• Statistically significant changes were observed in non-invasive tests (NITs) of fibrosis (Enhanced Liver Fibrosis score (ELF) and Vibration-Controlled Transient Elastography (VCTE)) and inflammation (alanine aminotransferase, ALT) compared with placebo at both doses.
• Glycemic control was maintained with minimal changes in HbA1C regardless of diabetic status, and blood pressure reductions were observed without changes in heart rate.

Sentiment

Score: 9

Explanation: The document reports overwhelmingly positive topline results for Pemvidutide's Phase 2b MASH trial, meeting its primary endpoint with high statistical significance for MASH resolution and demonstrating strong weight loss and liver fat reduction. The safety and tolerability profile is excellent, with very low discontinuation rates. While the primary fibrosis improvement endpoint was not statistically significant, the AI-based analysis and improvements in non-invasive tests suggest anti-fibrotic activity. Management expresses strong conviction and outlines a clear path to Phase 3, indicating a highly favorable outlook for the drug's development.

Positives

• Statistically significant MASH resolution without worsening of fibrosis was achieved in 59.1% (1.2 mg) and 52.1% (1.8 mg) of participants, significantly higher than 19.1% for placebo (p<0.0001 for both doses).
• Significant mean weight loss of 5.0% (1.2 mg) and 6.2% (1.8 mg) was observed at 24 weeks, compared to 1.0% for placebo (p<0.001), with the trajectory showing no plateauing.
• Robust liver fat reductions of 58.0% (1.2 mg) and 62.8% (1.8 mg) were achieved, significantly higher than 16.2% for placebo (p<0.001).
• Favorable safety and tolerability profile with very low adverse event-related discontinuations (0.0% for 1.2 mg and 1.2% for 1.8 mg) compared to 2.4% for placebo.
• No serious adverse events related to study medication or arrhythmias were reported.
• Supplemental AI-based analysis demonstrated statistically significant reductions in fibrosis, including 30.6% of participants receiving pemvidutide 1.8 mg achieving a 60% or more reduction in fibrosis compared to 8.2% receiving placebo (p<0.001).
• Statistically significant reductions were observed in non-invasive tests of fibrosis (ELF and VCTE) and inflammation (ALT).
• Glycemic control was maintained with minimal changes in HbA1C, and blood pressure was reduced without increases in heart rate.

Negatives

• Fibrosis improvement without worsening of MASH was not statistically significant in the primary intent-to-treat (ITT) analysis (31.8% for 1.2 mg and 34.5% for 1.8 mg vs. 25.9% for placebo).
• The stringent composite endpoint of MASH resolution and fibrosis improvement was not statistically significant (25.8% for 1.2 mg and 24.1% for 1.8 mg vs. 13.5% for placebo).
• Gastrointestinal adverse events such as nausea (41.2% for 1.8 mg vs. 14.1% placebo), vomiting (8.2% for 1.8 mg vs. 2.4% placebo), and diarrhea (21.2% for 1.8 mg vs. 8.2% placebo) were more common in pemvidutide-treated groups, although they led to low discontinuation rates.

Risks

• The success, cost, and timing of the Company's product candidate development activities and planned clinical trials are uncertain.
• There is a risk that positive results from current clinical studies may not necessarily be predictive of the results of future or ongoing clinical studies.
• Regulatory developments in the United States and foreign countries could impact the drug's approval and commercialization.
• The Company's ability to fund its operations is a risk factor.
• Potential for delays in regulatory review, manufacturing and supply chain interruptions, access to clinical sites, and patient enrollment.
• Adverse effects on healthcare systems and disruption of the global economy could impact operations.
• The impact of subject baseline characteristics, including body weight, on the success of future trials is a consideration.
• The reliability of the results of studies relating to human safety and possible adverse effects resulting from the administration of the Company's product candidates is a risk.
• The Company's ability to manufacture clinical trial materials on the anticipated timelines is not guaranteed.
• The success of future product advancements, including the success of future clinical trials, is uncertain.

Future Outlook

Altimmune plans to continue the IMPACT trial for a total of 48 weeks, with a final readout anticipated in the fourth quarter of 2025. The company intends to hold an End of Phase 2 meeting with the FDA in the fourth quarter of 2025, aiming for rapid progression to Phase 3. A Phase 2 trial in Alcohol-associated Liver Disease (ALD) is scheduled to commence in the third quarter of 2025. Management believes pemvidutide has the potential to disrupt the MASH treatment paradigm and suggests that a 2.4 mg dose in Phase 3 could achieve even greater weight loss.

Management Comments

• Vipin K. Garg, Ph.D., President and Chief Executive Officer of Altimmune: "These data represent an important step forward in the development of pemvidutide for the treatment of MASH and reinforce our conviction in its potential to disrupt the treatment paradigm in this serious and rapidly growing disease. Despite a prevalence expected to exceed 27 million by 2030 in the United States alone, current treatment options are limited. We are excited to continue our efforts to bring this potentially transformative therapy to MASH patients."
• Dr. Mazen Noureddin, Professor of Medicine at the Houston Methodist Hospital and Co-Chairman of the Board for Summit and Pinnacle Clinical Research: "The combination of MASH resolution and weight loss achieved at only 24 weeks is unique among drugs in development for MASH. The tolerability of pemvidutide was also impressive, with one of the lowest rates of AE-related drug discontinuations observed in any MASH clinical trial to date. The significant reduction in fibrosis in AI-based readings and its corroboration with established NITs suggest that pemvidutide has potent anti-fibrotic activity and that statistical significance on the fibrosis improvement endpoint could be achieved with longer durations of treatment."
• Dr. Scott Harris, Chief Medical Officer of Altimmune: "Based on the results generated in the IMPACT trial, pemvidutide demonstrated significant MASH resolution and encouraging evidence of fibrosis improvement at 24 weeks. Additionally, when one considers the weight loss and favorable tolerability associated with pemvidutide, we believe that there is a clear path to a successful End of Phase 2 meeting with the FDA in the fourth quarter of 2025, enabling rapid progression to Phase 3."

Industry Context

Metabolic dysfunction-associated steatohepatitis (MASH) is a serious and rapidly growing disease, with its prevalence in the United States alone expected to exceed 27 million by 2030. Current treatment options for MASH are limited, creating a significant unmet medical need. Altimmune's pemvidutide, a GLP-1/glucagon dual receptor agonist, is positioned as a potentially transformative therapy due to its unique combination of significant MASH resolution, substantial weight loss, and favorable tolerability observed at only 24 weeks, which is highlighted as potentially class-leading among drugs in development for MASH.

Comparison to Industry Standards

• **MASH Resolution without worsening of fibrosis (24 weeks):** Pemvidutide achieved 59.1% (1.2mg) and 52.1% (1.8mg) MASH resolution, which the company states is 'better than or comparable to other therapies, including those assessed at later timepoints' such as Efruxifermin (48 weeks), Pegozafermin (48 weeks), Efimosfermin (48 weeks), Resmetirom (52 weeks), Survodutide (48 weeks), and Semaglutide (72 weeks).
• **Fibrosis Improvement without worsening of MASH (24 weeks):** While not statistically significant in the primary ITT analysis (31.8% for 1.2mg, 34.5% for 1.8mg), the company notes that Pemvidutide's absolute fibrosis improvement is 'comparable or more favorable to most other MASH therapies' at 24 weeks, referencing the same list of comparators. The supplemental AI-based analysis showed statistically significant reductions in fibrosis, with 30.6% of 1.8 mg group achieving a 60% or more reduction compared to 8.2% placebo (p<0.001).
• **Weight Loss (24 weeks):** Pemvidutide demonstrated significant weight loss of 5.0% (1.2mg) and 6.2% (1.8mg), which is a critical element in MASH therapy and compares favorably to other MASH candidates that may not offer similar weight reduction profiles.
• **Tolerability:** Pemvidutide exhibited 'potentially best-in-class tolerability' with less than 1% treatment discontinuations due to adverse events (0.0% for 1.2mg, 1.2% for 1.8mg), which is cited as 'one of the lowest rates of AE-related drug discontinuations observed in any MASH clinical trial to date' compared to other MASH clinical trials.

Stakeholder Impact

• **Shareholders:** The highly positive clinical trial results are likely to significantly increase investor confidence and potentially lead to a positive impact on the company's stock price, indicating strong progress towards commercialization in a large market.
• **Patients (MASH):** Pemvidutide offers a promising new therapeutic option for MASH, a serious condition with limited current treatments, providing significant MASH resolution, weight loss, and a favorable tolerability profile.
• **Healthcare Providers:** The drug's efficacy in MASH resolution, coupled with its weight loss benefits and good tolerability, suggests it could become a valuable tool for clinicians managing patients with MASH.
• **Competitors:** The strong results, particularly the MASH resolution and tolerability profile, position Pemvidutide competitively against other drugs in development for MASH, potentially influencing the competitive landscape.

Next Steps

• Altimmune will host a conference call and live webcast on June 26, 2025, at 8:30 a.m. E.T. to discuss the results.
• Participants in the IMPACT trial will receive a total of 48 weeks of treatment, with a final readout anticipated in the fourth quarter of 2025.
• The Company plans to have an End of Phase 2 meeting with the FDA in the fourth quarter of 2025 to enable rapid progression to Phase 3.
• A Phase 2 trial in Alcohol-associated Liver Disease (ALD) is scheduled to commence in the third quarter of 2025.

Key Dates

Recommendation

Keywords

MASH, Pemvidutide, Altimmune, Phase 2b trial, metabolic dysfunction-associated steatohepatitis, GLP-1/glucagon dual receptor agonist, liver disease, weight loss, fibrosis, clinical trial results, biopharmaceutical, drug development, obesity, Alcohol Use Disorder, ALD