Pemvidutide advances toward Phase 3 after strong MASH fibrosis results
Noninvasive tests showed significant liver-scarring improvements vs. placebo
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About one year of treatment with Altimmune’s experimental therapy pemvidutide led to reductions in noninvasive markers of liver scarring (fibrosis) in people with metabolic dysfunction-associated steatohepatitis (MASH), a severe type of fatty liver disease.
That’s according to final results from the Phase 2b IMPACT clinical trial (NCT05989711), which tested two doses of pemvidutide against a placebo in 212 adults with biopsy-confirmed MASH and moderate to severe liver fibrosis.
Based on these findings, Altimmune plans to test pemvidutide in a registrational Phase 3 trial — a study designed to generate data that could support a future approval application if successful.
Company prepares for Phase 3 trial after FDA discussions
Altimmune recently met with the U.S. Food and Drug Administration (FDA) to discuss and align on key aspects of the upcoming Phase 3 study.
“With the benefit of FDA feedback and these 48-week data now in hand, we are greatly looking forward to progressing pemvidutide to a Phase 3 program which we intend to initiate in 2026,” Vipin Garg, PhD, Altimmune’s CEO, said in a company press release. “Strong evidence of antifibrotic improvements based upon non-invasive tests, combined with an attractive tolerability profile, highlight pemvidutide’s differentiation and potential to be a meaningful treatment option for the MASH patient community.”
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a type of fatty liver disease marked by excess fat buildup in the liver, usually linked to metabolic conditions such as obesity and diabetes.
In some people with MASLD, the disease progresses to MASH, where fat accumulation triggers liver inflammation and fibrosis. Over time, this damage can raise the risk of serious complications such as liver failure and liver cancer.
Pemvidutide is a subcutaneous (under-the-skin) injection that is designed to activate two receptors at the same time: GLP-1R, which helps regulate appetite and body weight, and GCGR, which helps control how the liver processes fat. By targeting both pathways, the therapy aims to reduce liver fat and potentially slow or lessen fibrosis.
These results reinforce that pemvidutide may address both liver-specific and metabolic drivers of MASH without compromising tolerability — three critical elements of a potential effective treatment for this patient population.
In an earlier Phase 1 trial (NCT05006885), pemvidutide was shown to reduce liver fat and body weight in people with MASLD.
The Phase 2b IMPACT trial evaluated the safety and effectiveness of 1.2 mg and 1.8 mg of pemvidutide compared with a placebo in people with MASH and moderate to severe liver fibrosis.
Top-line six-month results, announced last year, showed the trial met one of its main goals, with significantly more participants receiving either dose of pemvidutide achieving MASH resolution without worsening fibrosis compared with placebo.
For the trial’s other primary goal — the proportion of participants who had an improvement in fibrosis without MASH worsening — results favored pemvidutide, but the difference versus placebo did not reach statistical significance.
48-week results show meaningful changes on liver-scarring tests
Newly announced results include outcomes through 48 weeks, or nearly one year. Two noninvasive measures of liver fibrosis severity — Enhanced Liver Fibrosis (ELF) and Liver Stiffness Measurement (LSM) — showed significant reductions with both pemvidutide doses compared with placebo.
More than a quarter of patients on pemvidutide achieved both a reduction of at least 0.5 points in ELF and a 30% drop in LSM. This combined response was seen in 27.8% of participants in the 1.2 mg group and 32.4% in the 1.8 mg group, compared with 3.2% of those given placebo.
“The magnitude of response versus placebo on measures such as ELF and LSM at 48 weeks makes these data particularly compelling, as these noninvasive markers have been shown to correlate with [biopsy-based] fibrosis stage,” said Mazen Noureddin, MD, principal investigator of the IMPACT trial at Houston Methodist Hospital.
Measures of liver damage, liver inflammation, and liver fat content also showed statistically significant reductions with both pemvidutide doses compared with placebo.
Treatment was also associated with significantly greater weight loss: participants in the 1.2 mg group lost 4.5% of their body weight and those in the 1.8 mg group lost 7.5%, compared with 0.2% in the placebo group. No plateau in weight loss was seen at 48 weeks with the higher dose.
No serious or severe adverse events related to pemvidutide were reported during the yearlong study. Altimmune also reported that fewer participants stopped treatment due to side effects in the pemvidutide groups (0% at 1.2 mg and 1.2% at 1.8 mg) than in the placebo group (3.5%).
“These results reinforce that pemvidutide may address both liver-specific and metabolic drivers of MASH without compromising tolerability — three critical elements of a potential effective treatment for this patient population,” Noureddin said. “I am encouraged by the dose response observed and the performance of the 1.8 mg [group] and I am eager to see this differentiated therapeutic candidate advance into Phase 3 evaluation.”
