Based on a quantitative systems pharmacology (QSP) computational model, pemvidutide’s GLP-1/glucagon dual agonism could have additive effects on MASH resolution and fibrosis improvement compared with GLP-1 alone Pemvidutide is currently being evaluated in the ongoing Phase 2b IMPACT trial in subjects with MASH “These data, coupled with MOMENTUM Phase 2 obesity trial results that showed class-leading lean mass preservation in body composition, further reinforce the opportunity for pemvidutide to distinguish itself broadly from approved therapies and other clinical candidates targeting MASH and obesity,” said Vipin K. Garg, Ph.D., President and Chief Executive Officer of Altimmune. “The balanced GLP-1 and glucagon dual agonism of pemvidutide represents a potentially differentiated approach to achieving clinically meaningful reductions in body weight, liver fat, and lipids to ameliorate MASH and address the many MASH-associated co-morbidities.” The data presented are summarized below:
WED-212 (Abstract #3002): Pemvidutide treatment is associated with improvement in non-invasive tests indicating greater likelihood of histologic response in subjects with metabolic dysfunction-associated steatotic liver disease: a 24-week, randomized, double-blind, placebo-controlled trial 64 subjects who participated in the Phase 1 study of pemvidutide in MASLD were evaluated for changes in FibroScan®-AST (FAST) over 24 weeks of treatment. A subset of subjects with baseline ALT ≥ 30 IU/L were also evaluated for changes in MRI-PDFF and ALT scores. Up to 75% of subjects with intermediate-to-high risk of MASH progression (FAST ≥ 0.35) at baseline who received pemvidutide had their risk reduced to low (FAST Up to 60% of subjects achieved a reduction of both MRI-PDFF (≥ 30%) and ALT (≥ 17 IU/L) at Week 24 compared with 0% in subjects receiving placebo. Simultaneous reductions in MRI-PDFF and ALT have been shown in other MASH clinical trials to be associated with a significantly greater likelihood of achieving MASH resolution. A strong correlation was observed between clinically reported and QSP predicted effects of pemvidutide on weight loss and liver fat content. The QSP model predicted pemvidutide 1.8 mg would result in complete resolution of MASH and a 1-point median improvement in fibrosis by Week 24. WED-251 (Abstract #2985): Plasma lipidomic profiling of subjects with overweight or obesity following treatment with the glucagon-like peptide 1/glucagon dual receptor agonist pemvidutide: an investigation of lipid signatures associated with metabolic dysfunction-associated steatohepatitis Plasma lipidomic profiling was performed on samples collected during Phase 1 studies of pemvidutide in subjects with overweight or obesity, with or without MASLD. Subjects treated with pemvidutide had significantly decreased serum lipids from baseline, including glycophospholipids, sphingolipids and other inflammatory lipid subspecies associated with MASH and cardiovascular disease. Pemvidutide treatment was also associated with reduced bile acid dysregulation. Obesity and insulin resistance, two key risk factors for MASH and MASLD, contribute to bile acid dysregulation. Evidence has shown that bile acid dysregulation worsens as MASLD progresses. The posters presented at the EASL International Liver Congress™ 2024 are accessible on the Events section of the Altimmune website.
Pemvidutide is a novel, investigational, peptide-based GLP-1/glucagon dual receptor agonistGLP-1/glucagon dual receptor agonist in development for the treatment of obesity and MASH. Activation of the GLP-1 and glucagon receptors is believed to mimic the complementary effects of diet and exercise on weight loss, with GLP-1 suppressing appetite and glucagon increasing energy expenditure. Glucagon is also recognized as having direct effects on hepatic fat metabolism, which is believed to lead to rapid reductions in levels of liver fat and serum lipids. In clinical trials to date, once-weekly pemvidutide has demonstrated compelling weight loss, robust reductions in triglycerides, LDL cholesterol, liver fat content and blood pressure. The U.S. FDA has granted Fast Track designation to pemvidutide for the treatment of MASH. Pemvidutide recently completed the MOMENTUM Phase 2 obesity trial and is being studied in the ongoing IMPACT Phase 2b MASH trial. Follow @Altimmune, Inc. on LinkedIn
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