Altimmune (NASDAQ:ALT) executives highlighted recent clinical and regulatory milestones for pemvidutide and outlined plans to advance a Phase 3 program in metabolic dysfunction-associated steatohepatitis (MASH) during a presentation at the Leerink Partners Global Healthcare Conference.
2025 readouts and FDA feedback set stage for Phase 3
Chief Executive Officer Jerry Durso said 2025 featured two readouts from the company’s Phase 2 MASH trial, with 24-week data presented midyear and 48-week data presented in December. Durso said the results provided a clearer view of what pemvidutide could deliver in the MASH population.
Mechanism and differentiation: emphasis on “balance” and tolerability
Durso and Chief Medical Officer Christophe Arbet-Engels focused on pemvidutide’s dual agonist mechanism (glucagon and GLP-1) and argued that the product’s “1-to-1 ratio” of receptor agonism underpins potential differentiation. They said this approach is intended to pair glucagon’s direct effects on the liver with GLP-1’s metabolic benefits.
Arbet-Engels contrasted pemvidutide with survodutide, which he said has a “very different ratio” that is “close to seven to one,” describing it as more focused on GLP-1 and potentially less on direct liver effects. He also cited tolerability as a key distinction, stating that pemvidutide uses an “EuPort domain” linking the peptides to support a delayed Tmax and lower Cmax. In the company’s Phase 2 study, he said more patients stayed on drug, and noted that discontinuations were “less than placebo rate.” By comparison, he referenced discontinuation rates he attributed to survodutide of roughly 23% to 26%.
Phase 2 MASH data and rationale for a 52-week histology endpoint
In discussing the Phase 2 IMPACT study, Durso said the histology endpoint occurred at 24 weeks and suggested that timeframe may have been “a little early” to demonstrate a statistically significant fibrosis effect, citing variability and placebo response challenges in biopsy-based trials. He added that two drugs later approved in MASH missed endpoints in Phase 2, then used longer Phase 3 timelines and achieved success.
Arbet-Engels said the company went to the FDA with the 24-week data because it showed MASH resolution, which he described as a prerequisite for demonstrating fibrosis improvement. He said the company saw indications of an anti-fibrotic effect across molecular and clinical measures and that 48-week data using non-invasive tests showed continued improvement in markers “going in directions that are very solidly antifibrotic.” Both executives said they are confident that a 52-week histology endpoint is appropriate for Phase 3.
The team also said Phase 3 will evaluate the 1.8 mg dose and include a 2.4 mg dose as a potential upside opportunity on efficacy, including added weight loss.
Trial design details: titration and AIM-MASH implementation
Arbet-Engels said the Phase 2 study did not use titration, unlike other injectable options that often require multi-step titration schemes. For Phase 3, he said the company plans to introduce a “simple approach” to titration, describing it as one step for the 1.8 mg dose and a one- or two-step approach for 2.4 mg. He said the intent is to improve tolerability further and support testing the higher dose.
Altimmune also discussed incorporating the FDA-cleared AIM-MASH Assist tool from PathAI for histology evaluation in Phase 3. Arbet-Engels said the tool is intended to reduce variability and streamline review by helping point out histologic features on digital slides, while maintaining the pathologist’s responsibility for the final interpretation. Durso and Arbet-Engels characterized the use of AIM-MASH as a potential “upside,” while emphasizing the company is taking a conservative approach to powering the study.
Non-invasive tests, global regulatory alignment, and other liver programs
On the regulatory outlook for non-invasive tests (NITs), Arbet-Engels said the FDA was “pretty clear” it is premature to use NITs as registrational endpoints today, even as clinical practice moves ahead. He said the agency could evolve its stance during the conduct of the trial, and the company is collecting multiple NITs in Phase 3, including ELF and liver stiffness measures such as VCTE, to preserve flexibility if regulators pivot.
The company also said its Phase 3 design includes two cohorts: a biopsy-proven cohort for the primary 52-week histology endpoint and a second cohort identified via NITs intended to contribute to safety and long-term outcomes.
Arbet-Engels said Altimmune is pursuing a global program and expects its approach to be aligned with European regulators, including the EMA and MHRA, based on work with regulatory consultants.
Beyond MASH, Durso said Altimmune has two Phase 2 trials in alcohol-related indications:
- Alcohol use disorder (AUD): The company is guiding to top-line data in the third quarter, with heavy drinking days as the primary endpoint and additional measures including PEth testing to provide a more objective read given potential underreporting.
- Alcohol-related liver disease (ALD): The company expects to complete enrollment and cited rationale tied to pemvidutide’s effects on both the liver and craving/reward pathways, as well as the importance of tolerability in these populations.
Executives said next steps in AUD will depend on the data, noting that a regulatory pathway exists and that the company intends to provide an update after results are available.
About Altimmune (NASDAQ:ALT)
Altimmune, Inc is a clinical-stage biopharmaceutical company headquartered in Gaithersburg, Maryland, dedicated to the development of vaccines and immunotherapeutics. The company leverages proprietary technology platforms to create intranasal vaccine candidates and novel therapies targeting liver diseases and metabolic disorders. Altimmune’s approach emphasizes the stimulation of both systemic and mucosal immune responses to address unmet medical needs in infectious and chronic conditions.
Among its lead programs, NasoVAX is an investigational intranasal influenza vaccine designed to provide broad, long-lasting protection through a single, non-invasive dose.
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