Pemvidutide Preserves Lean Mass With Weight Loss of Nearly 16%: MOMENTUM Phase 2 Trial

Pemvidutide, an investigational dual incretin/glucagon receptor agonist, reduced body weight by 15.6% among adults with obesity, with fat loss of 78.1%, a strong indication that the drug is able to reduce excess weight with minimal loss of lean muscle mass.¹

The findings, from the phase 2 MOMENTUM trial, were presented at the 84th American Diabetes Association (ADA) Scientific Sessions, June 21-24, in Orlando, Florida.

Full analysis of the study’s body composition analysis showed what biopharmaceutical company and pemvidutide developer Altimmune in a press release called “class-leading” mass preservation with only 21.9% of the observed weight loss attributable to lean mass.”²

“Obesity is a multifactorial disease, and patients will need a variety of treatment options that fit their specific needs and comorbidities,” primary investigator Louis J Aronne, MD, director of the Comprehensive Weight Control Center in the Division of Endocrinology, Diabetes & Metabolism at Weill Cornell Medicine” said in the release.² “These latest findings are particularly exciting given that pemvidutide has not only demonstrated significant weight loss but an impressive ability to preserve lean mass.”²

Aronne and colleagues enrolled 391 participants with overweight and at least one related comorbidity or obesity and without type 2 diabetes, according to the study abstract.¹ Mean age of the cohort at baseline was 50 years and three-quarters were women. At baseline, MOMENTUM participants had mean body mass index (BMI) of 37 kg/m² and a mean body weight of 104 kg.¹

Study investigators randomly assigned participants 1:1:1:1 to receive weekly subcutaneous pemvidutide at doses of 1.2 mg, 1.8 mg, 2.4 mg or placebo for 48 weeks in conjunction with dietary modification and physical activity. The 2.4 mg dose was titrated over the first 4 weeks of treatment, according to the study.¹ A subgroup of 50 participants was evaluated in a body composition analysis, Altimmune said.²

After 48 weeks of treatment, the mean reductions in body weight for the 3 pemvidutide doses were 10.3% (1.2 mg), 11.2% (1.8 mg), and 15.6% (2.4 mg) compared to placebo (2.2%) (P <.001 vs placebo for all doses), the study abstract states.¹ A “near-linear continued weight loss” was described for participants on the 2.4 mg dose at the end of treatment.² The researchers also reported that of the participants receiving the 2.4-mg pemvidutide half (51.8%) achieved 15% and greater weight loss and nearly one-third (32.1%) reached a 20% or greater weight loss. Furthermore, close to half (48%) of those receiving 2.4 mg “had resolution of baseline obesity by trial conclusion,” Aronne et al wrote in the abstract.¹ They also reported body weight reductions of 20% or greater in 2.0% of placebo-treated participants, and in 10.% and 9.5% of those who received 1.2 mg and 1.8 mg of pemvidutide, respectively.²

Findings from the full MRI-based body composition analysis of 50 participants who received pemvidutide demonstrated mean weight loss of 78.1% attributable to fat and a far less mean loss of lean mass of 21.9%, as mentioned.²

Beyond reduction in body weight, Aronne and colleagues found treatment with pemvidutide led to statistically significant reductions in serum lipids among those with elevated levels at baseline of up to 55.8% (triglycerides), 20.0% (total cholesterol) and 21.8% (LDL-C) at week 48.¹ The treatment was also associated with blood pressure improvements, causing no imbalances in cardiac events, arrhythmias, or clinically meaningful increases in heart rate, according to the press release.²

Adverse events (AE) were mild to moderate, according to the study abstract, with 1 drug-related severe AE.¹

“With its favorable safety profile to-date and the potential to drive clinically meaningful improvements in other obesity-related conditions such as dyslipidemia and hypertension, pemvidutide could offer a highly promising, long-term treatment option for multiple segments of the obese patient population to safely and effectively manage body weight,” Aronne added in the press release.²

The novel glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist is being investigated for treatment of obesity and also for metabolic dysfunction-associated steatohepatitis (MASH). The US FDA has granted Fast Track designation to pemvidutide for the treatment of MASH.²

References:
1. Aronne LJ, Harris MS, Roberts MS, et al. Pemvidutide, a GLP-1/glucagon dual receptor agonist, in subjects with overweight or obesity—a 48-week, placebo controlled, phase 2 (MOMENTUM) trial. Abstract presented at: American Diabetes Association (ADA) 84th Scientific Sessions; June 21 - 24, 2024; Orlando, Florida. Accessed June 24, 2024. https://eppro02.ativ.me/web/page.php?page=IntHtml&project=ADA24&id=656
2. Altimmune presents data from phase 2 MOMENTUM trial of pemvidutide in obesity during oral presentation at the American Diabetes Association’s 84th scientific sessions. News release. Altimmune. June 23, 2024. Accessed June 24, 2024. https://ir.altimmune.com/news-releases/news-release-details/altimmune-presents-data-phase-2-momentum-trial-pemvidutide