Altimmune has enrolled the first subject in the 48-week Phase 2 MOMENTUM trial evaluating the safety and efficacy of pemvidutide in subjects with obesity or overweight. Pemvidutide is a novel, investigational GLP-1/glucagon dual receptor agonist under development for the treatment of obesity and non-alcoholic steatohepatitis (NASH). The company also announced the completion of enrolment in its 12-week Phase 1b clinical trial of pemvidutide in subjects with non-alcoholic fatty liver disease (NAFLD).
Pemvidutide is a novel, investigational, peptide-based GLP-1/glucagon dual receptor agonist in development for the treatment of obesity and NASH. 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. By combining GLP-1 and glucagon activity in a single peptide, pemvidutide has the potential to achieve weight loss comparable to bariatric surgery.
Pemvidutide also has been shown to increase the breakdown of fat and its mobilization within the liver, which may have beneficial effects on not only fat-related liver diseases like NASH, but also insulin resistance, a common problem in people with obesity. Pemvidutide incorporates the EuPort domain, a proprietary technology that increases its serum half-life for weekly dosing while slowing the entry of pemvidutide into the bloodstream, which may improve its tolerability. In a Phase 1 clinical trial, pemvidutide demonstrated striking reductions in body weight, liver fat and serum lipids.
The 48-week MOMENTUM trial is being conducted at approximately 25 sites in the US with Dr Lou Aronne, a leading authority in obesity and obesity clinical trials, serving as the Principal Investigator. The randomized, placebo-controlled trial is expected to enrol approximately 320 non-diabetic subjects randomised 1:1:1:1 to receive either 1.2mg, 1.8mg, 2.4mg pemvidutide or placebo weekly for 48 weeks. The primary endpoint of the trial is the relative (percent) change in body weight at 48-weeks compared to baseline, with additional readouts including metabolic and lipid profiles, cardiovascular measures and glucose homeostasis. An interim analysis is planned to assess changes in body weight after 24 weeks of treatment, expected in the fourth quarter in 2022.
“Initiation of the Phase 2 MOMENTUM obesity trial marks an important milestone in the development of pemvidutide,” explained Dr Scott Harris, Chief Medical Officer at Altimmune. “Built on a foundation of compelling Phase 1 clinical data, we see a great potential for pemvidutide to address the serious and widespread disease of obesity and its debilitating consequences.”
Results from a Phase 1 trial of pemvidutide in individuals with obesity or overweight showed that 12 weekly subcutaneous doses of pemvidutide resulted in an average weight loss of 10.3%, or approximately 20lbs, without diet or lifestyle modification. If these effects continue over the 48-week study as anticipated, weight loss approaching or equalling those of bariatric surgery may be achieved. Side effects were mild to moderate, with no serious or severe treatment-emergent adverse events, even without the dose-titration schedules commonly used by other therapeutics in this class.
Significant progress has also been made in the development of pemvidutide for the treatment of NASH, including the completion of enrolment in a 12-week Phase 1b trial in subjects with NAFLD, and the initiation of a blinded, 12-week NAFLD extension trial. The 12-week Phase 1b NAFLD trial is designed to assess the effects of pemvidutide on liver fat in subjects with obesity or overweight and liver fat content of 10% or greater as measured by MRI-PDFF. Approximately 72 subjects with or without diabetes are being randomised 1:1:1:1 to receive pemvidutide 1.2 mg, 1.8 mg, 2.4 mg or placebo weekly over the 12 weeks of treatment.
The primary endpoint of the trial is the reduction in liver fat by MRI-PDFF, but a key secondary endpoint is percent weight loss at the end of 12 weeks of treatment, reflecting the fact that obesity is a key driver of NAFLD and its more advanced form, NASH. A data readout from the 12-week trial is expected in then third quarter 2022, and it is expected that the cumulative weight loss at 24 weeks in combination with the extension trial will be reported out in the fourth quarter in 2022.