Pemvidutide (proposed INN, formerly known as ALT-801) is a novel, investigational, peptide-based GLP-1/glucagon dual receptor agonist in development for the treatment of obesity and NASH. Pemvidutide incorporates the EuPortTM domain, a proprietary technology that increases its serum half-life for weekly dosing and may slow the entry of pemvidutide into the bloodstream and improve its tolerability. Pemvidutide also has been shown to increase the burning of fat within the liver, which could have beneficial effects on insulin resistance, a common problem in people with obesity. In a Phase 1 clinical trial, pemvidutide demonstrated striking reductions in body weight, liver fat and serum lipids.
What is Pemvidutide
Pemvidutide for the Treatment of Obesity
Pemvidutide is a dual receptor agonist that can activate both GLP-1 and glucagon receptors and thereby may mimic the complementary effects of diet and exercise on weight loss. Here, its GLP-1 activity is expected to suppress appetite while its glucagon activity is expected to increase energy expenditure and the burning of fat. By combining GLP-1 and glucagon activity in a single peptide, pemvidutide has the potential to achieve weight loss comparable to bariatric surgery.
A Phase 1 randomized, placebo-controlled, clinical trial of pemvidutide in obese and overweight volunteers has been completed. After receiving 12 weekly doses of pemvidutide, significant weight loss occurred in each of the pemvidutide treated groups compared to placebo. At the 1.8 mg dose, 100% participants lost at least 5% of weight, and more than half lost more than 10% of the body weight in 12 weeks.
In addition to the pronounced weight loss observed in the Phase 1 study, participants receiving pemvidutide also experienced significant reductions in circulating lipids that are associated with cardiovascular disease. The declines in low density lipoprotein cholesterol (LDL-C) and triglycerides after 12-weeks of treatment were similar to what is achieved with currently prescribed drugs for hypercholesteremia and hypertriglyceridemia.
Pemvidutide for the Treatment of NASH
It is estimated that nearly 80 million1 people in the United States have NAFLD, and it is now the most common form of liver disease in children. If unaddressed, the condition may progress to NASH, where excess fat in the liver causes chronic inflammation leading to fibrosis, and eventually cirrhosis. Altimmune believes the treatment of obesity is the cornerstone of treating NASH and its co-morbidities and views the treatment of NASH as a significant unmet medical need that can be addressed through significant weight loss and reduction in liver fat content. Previous studies of significant weight loss, such as following bariatric surgery, have shown that weight loss of 10% or greater can reverse the disease effects of NASH and reverse liver fibrosis2.
In our Phase 1 clinical trial of pemvidutide in obese and overweight volunteers we looked at the effect of pemvidutide on the amount of fat in the liver in addition to overall weight loss. In a subset of participants with liver fat content between 5% and nearly 20% we observed that pemvidutide reduced the liver fat to below detectable levels in just 6 weeks.
1 Arshad T, Golabi P, Henry L, Younossi ZM. Epidemiology of Non-alcoholic Fatty Liver Disease in North America. Curr Pharm Des. 2020;26(10):993-997. doi: 10.2174/1381612826666200303114934. PMID: 32124690.
2 Promrat et al Hepatology 2010; Glass et al Dig Dis Sci 2015; Vilar-Gomez et al Gastroenterology 2015; Marchesini et al Hepatology 2016; Koutowkidis et al JAMA Intern Med 2019