Pemvidutide seen to lower liver fat in MASLD patients in Phase 1 trial

Potential therapy now being tested in enrolling study of adults with MASH

by Marisa Wexler, MS | August 5, 2024

A pair of hands, a stethoscope, and a handful of oral medications surround a graph labeled

Pemvidutide, Altimmune’s experimental therapy, significantly reduced liver fat and inflammation, as well as body weight, among overweight or obese people with metabolic dysfunction-associated steatotic liver disease (MASLD), a form of fatty liver disease.

Results of the Phase 1 clinical trial (NCT05006885) were detailed in the study “Effect of pemvidutide, a GLP-1/glucagon dual receptor agonist, on MASLD: A randomized, double-blind, placebo-controlled study,” published in the Journal of Hepatology.

A Phase 2b trial called IMPACT (NCT05989711) now is testing pemvidutide against a placebo in up to 190 adults with metabolic dysfunction-associated steatohepatitis (MASH), a severe form of MASLD. Participants are being recruited at more than a dozen sites across the U.S., including one in Puerto Rico, with plans to open sites across Australia.

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“We look forward to sharing results from our ongoing biopsy-driven Phase 2b IMPACT trial of pemvidutide in MASH early next year,” Vipin K. Garg, PhD, president and CEO of Altimmune, said in a company press release.

MASLD, previously known as nonalcoholic fatty liver disease or NAFLD, is a disorder marked by the abnormal buildup of fat in the liver that’s linked to metabolic conditions, such as obesity or type 2 diabetes.

In serious cases, MASLD can progress to MASH, which is marked by liver inflammation and scarring (fibrosis) that can lead to serious long-term liver damage.

“MASLD is estimated to affect 25% of adults globally, with between 20% and 30% of patients progressing to MASH, making this an area of great unmet medical need,” Garg said.

Pemvidutide, formerly ALT-801, aims to reduce the buildup of liver fat by simultaneously activating two proteins: GLP-1R, which regulates food intake and body weight, and GCGR, which promotes liver fat breakdown to produce energy and reduces liver fat production.

Other MASLD therapies in development target GLP-1R, but pemvidutide is considered to be somewhat unique in its action on GCGR as well.

“Unlike other … therapies that lack [GCGR] activity, pemvidutide has a direct effect on [liver] fat metabolism, providing a mechanism for potentially more potent reductions in liver fat than that achieved through weight loss alone,” said Scott Harris, MD, Altimmune’s chief medical officer.

The U.S.-based Phase 1 trial explored the efficacy and safety of pemvidutide in 95 overweight to obese adults with MASLD. Most (75%) were of Hispanic ethnicity, and nearly one-third (29%) had type 2 diabetes.

Participants were randomly assigned to weekly under-the-skin injections of one of three doses of pemvidutide (1.2, 1.8, or 2.4 mg) or that of a placebo for 12 weeks (about three months).

Significant drops in fat liver content seen with treatment relative to placebo

The study’s main goal was to evaluate the effect of pemvidutide on liver fat content, as measured by MRI scans. At study’s start, most patients had a liver fat content higher than 20%, while a typical healthy liver is usually less than 5% fat.

Results showed that relative fat content was reduced by 46.6% in the 1.2 mg pemvidutide group, 68.5% in the 1.8 mg group, and 57.1% in the 2.4 mg group, while patients given a placebo experienced a 4.4% relative drop. Differences between each pemvidutide group and the placebo group were statistically significant.

The total amount of fat in the liver was cut by at least a third in most pemvidutide-treated patients (65%-94.4%), compared with 4.2% among those receiving a placebo. Liver fat normalization was achieved by up to 55.6% of those given pemvidutide and by none on the placebo. The most dramatic results were seen with the 1.8 mg dose.

Pemvidutide treatment also was associated with significantly greater reductions in body weight and blood levels of alanine aminotransferase (ALT), a marker of liver inflammation, meeting the trial’s secondary goals. Again, treatment with the 1.8 mg dose led to the greatest body weight loss, by 4.3%, and greatest ALT level drop, by 13.8%.

Markers of liver fibrosis also were reduced to a greater extent with pemvidutide.

“With nearly all subjects achieving 30% or more reductions in liver fat content after only 12 weeks of treatment, this study demonstrates the potential of pemvidutide to achieve class-leading effects in the treatment of MASH,” Garg said.

Researchers noted, however, that most trial participants did not have notable liver inflammation or fibrosis at study’s start, so it’s not possible to fully extrapolate findings to what might be seen in people with MASH.

Further reductions in liver fat were seen with longer treatment, Altimmune stated.

“Although not reported in this publication, the Phase 1 trial was extended for an additional 12 weeks, which resulted in up to 76.4% relative reduction in liver fat and further improvement in [liver] inflammation, and we look forward to the publication of these data in the near future,” Harris said.

Pemvidutide was generally safe and well tolerated, without serious treatment-related side effects. The most commonly reported adverse event while on the therapy was nausea (35.7%), which was mostly mild in severity.

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About the Author

Marisa Wexler, MS Marisa holds a Master of Science in cellular and molecular pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. Her areas of expertise include cancer biology, immunology, and genetics, and she has worked as a science writing and communications intern for the Genetics Society of America.