ORLANDO – Altimmune is back with a full Phase 2 analysis of its “double G” drug pemvidutide, with the company touting it is much better in preserving lean mass and regulating lipids than previously thought.
In the 48-week MOMENTUM trial, 21.9% of the total weight that patients lost during the study was lean mass — compared to the 25.5% in the partial analysis announced in March. In the new analysis, 78.1% of the total weight loss was attributable to fat, compared to 74.5% in the partial analysis. The data come from 50 patients in MOMENTUM who underwent a full MRI analysis. The trial had 391 participants.
Scott Harris“That’s better than any of the other compounds that have announced on this [lean mass loss] data,” Altimmune CMO Scott Harris told Endpoints News on the sidelines of the American Diabetes Association’s scientific sessions. “And we know that diet and exercise, when you just naturally lose weight, it’s about 25% [lean mass loss],” he added.
“[Pemvidutide is] at least as good as diet and exercise, which is the goal of pharmacologic therapy — to mimic what you do naturally and not exceed it,” he said.
Pemvidutide is a GLP-1/glucagon dual receptor agonist that also showed an overall average 15.6% weight loss. Altimmune is still in the process of looking for a Phase 3 partner for pemvidutide. While a detailed Phase 3 plan has not yet been announced, it will include endpoints of weight loss and markers of cardiovascular risk, like serum lipids and liver fat, according to the company.
Lean body mass is everything in the body that isn’t fat and includes bones, organs and muscle. Preservation of lean body mass has become a key conversation around GLP-1 efficacy in weight loss as companies are no longer simply aiming to help patients reduce the number on the scale, but ensure muscle mass is protected.
Harris referenced Novo Nordisk’s Wegovy, which has a mention of lean body mass issues on its label. In the cardiovascular outcomes trial for the GLP-1 agonist, there were more fractures in the hip and pelvis in patients on the drug than placebo. In female patients, 1% reported fractures compared to 0.2% with placebo. In patients 75 and older, 2.4% reported fractures compared to 0.6% on placebo.
“Now we’re talking about the quality of weight loss,” Harris said. “We think that the focus — which has always been on acute weight loss — will shift to chronic weight management and whether it’s safe management and maintenance of that weight.”
Also at the confab, Altimmune said that pemvidutide helped improve cardio-inflammatory lipids like total cholesterol (28% reduction), low-density lipoprotein cholesterol (26% reduction) and triglycerides (38% reduction).
The lipid reduction was not correlated to weight loss, which suggests that its candidate’s lipid effects were “due to the direct impact of pemvidutide” on lipid metabolism, the company said. The drug also “significantly reduced” other lipids that have an association with cardiovascular disease and other biomarkers of systemic inflammation that are known to cause heart failure.
Altimmune president and CEO Vipin Garg told Endpoints that the company would “absolutely, eventually” conduct a cardiovascular risk trial that would study pemvidutide. “That’s what you have to do to show the benefit,” Garg added. “Intuitively, it makes sense that we should have even more cardiovascular benefit than what we’re seeing with the current crop of GLP-1 drugs.”
The company’s stock took a dive in 2023 because, in pemvidutide’s safety profile, nearly a quarter of patients discontinued the drug and half of them did so because of gastro issues. This is despite interim data showing a placebo-adjusted weight loss of 9.7% at week 24 of 48, which is comparable to semaglutide and tirzepatide.
Since Altimmune’s data released over the weekend, the stock $ALT has risen again nearly 8% to $6.92.
In its latest financial report released in May, the company had cash, cash equivalents and short-term investments of $182.1 million as of March 31. The company also said in the report that it plans to meet with the FDA later in the third quarter of this year with a data package for pemvidutide, including from the MOMENTUM trial.
For now, pemvidutide is in the Phase 2b IMPACT trial in metabolic dysfunction-associated steatohepatitis (MASH), with a primary completion date of February 2025, according to ClinicalTrials.gov.