Efinopegdutide

Despite the primary endpoint miss, Altimmune hailed pemvidutide as the “first product candidate to demonstrate significant MASH effects and weight loss at 24 weeks.”\n Altimmune’s GLP-1/glucagon dual receptor agonist achieved a hit and a miss when it came to the dual goals of a phase 2 metabolic dysfunction-associated steatohepatitis (MASH) study, while still showcasing the asset’s weight loss potential.Investors appeared disheartened by the results, sending Altimmune’s stock down 59% to $3.18 in premarket trading Thursday from a Wednesday closing price of $7.71.The trial enrolled 212 patients with the liver disease who received weekly subcutaneous doses of either 1.2 mg or 1.8 mg of the drug, called pemvidutide, or placebo. A total of 59.1% of the 1.2-mg cohort and 52.1% of the 1.8-mg cohort saw their MASH resolve without a worsening of fibrosis, compared to 19.1% of the placebo cohort, hitting one of the trial’s primary endpoints.However, when it came to the other key endpoint of improving fibrosis while not worsening MASH, pemvidutide was unable to demonstrate a statistically significant difference. Specifically, 31.8% and 34.5% of the pemvidutide cohorts achieved this goal, respectively, compared to 25.9% of those on placebo.Digging into the study’s secondary endpoints to find sources of optimism, Altimmune pointed out that 30.6% of patients on 1.8 mg pemvidutide saw a 60% or greater reduction in their fibrosis, compared to 8.2% of the placebo group.“Together, these data suggest strong evidence of anti-fibrotic activity of pemvidutide in the MASH population,” Altimmune concluded in the June 26 release. When it came to Altimmune’s potential in the red-hot obesity space, the pemvidutide cohorts saw 5% and 6.2% mean weight loss, respectively, compared to 1% for placebo. There were also no signs of this weight loss trajectory plateauing at 24 weeks, the biotech noted.“Based on the results generated in the IMPACT trial, pemvidutide demonstrated significant MASH resolution and encouraging evidence of fibrosis improvement at 24 weeks,” Altimmune Chief Medical Officer, Scott Harris, M.D., said in the release.“Additionally, when one considers the weight loss and favorable tolerability associated with pemvidutide, we believe that there is a clear path to a successful end-of-phase 2 meeting with the FDA in the fourth quarter of 2025, enabling rapid progression to phase 3,” Harris added.William Blair analysts were less supportive, describing this morning\'s MASH results as “underwhelming” and suggesting that the weight loss data was “non-differentiating.”The latest weight loss data follow a phase 2 obesity trial of pemvidutide that in recent years has not only linked the GLP-1/glucagon agonist to mean weight loss of 15.6% after 48 weeks but suggested that most of the weight lost is from fat rather than muscle.MASH—previously known as nonalcoholic steatohepatitis—has proven an elusive target for pharma, but several drugmakers are starting to find increasing success in the metabolic liver disease, including via GLP-1 routes. Novo Nordisk is awaiting an FDA decision on approving semaglutide, the ingredient in its blockbuster GLP-1 obesity drug Wegovy, for MASH after it demonstrated improvements in liver fibrosis in a phase 3 trial.There has also been promising MASH data from other GLP-1 drugs like Eli Lilly’s GIP/GLP-1 co-agonist tirzepatide and Boehringer Ingelheim’s glucagon/GLP-1 agonist survodutide.

A little known South Korean biotech said Monday that its experimental treatment yielded encouraging results in the race to treat metabolic dysfunction-associated steatohepatitis (MASH). D&D Pharmatech reported that DD01 hit the main goal of a Phase II trial — and investors took notice, sending the company's stock soaring to the 30% daily limit on Korea's KOSDAQ exchange.The once-weekly dual GLP-1/glucagon receptor agonist was evaluated in 67 overweight or obese individuals with MASH. Treatment began with a two-week lead-in 20-mg subcutaneous dose, followed by a maintenance dose of 40 mg administered once weekly.After 12 weeks, results showed that 75.8% of patients on DD01 had at least a 30% drop in liver fat, compared to 11.8% of those on placebo. The drug was associated with a 62.3% relative reduction in liver fat compared to 8.3% with placebo.Additionally, 72.7% of subjects had their liver fat reduced by half, compared to 5.9% for placebo; and 48.5% reached normalisation — defined as 5% or less — while no one in the placebo group reached that mark.Beyond liver fat reduction, DD01 also significantly improved liver stiffness and other non-invasive markers of disease, as well as body weight and HbA1c, although the study population was not selected to be diabetic.CEO Seulki Lee called the results "remarkably positive," and said that "the magnitude of improvements is equivalent to what has been achieved only after longer-term treatment with FGF and GLP-1 based drugs already validated with histology data in MASH."The treatment was generally well tolerated, though as with other GLP-1-based therapies, gastrointestinal (GI) side effects were most common. Three participants dropped out due to GI issues, but the company described events as "generally mild to moderate, but transient and manageable."Several companies have been vying for a piece of the MASH pie. Novo Nordisk's semaglutide, branded as Ozempic for diabetes and Wegovy for weight loss, recently succeeded in the Phase III ESSENCE trial, earning a priority review from US regulators for MASH.Eli Lilly's competing drug tirzepatide, sold as Mounjaro/Zepbound, also hit met the primary endpoint of the Phase II SYNERGY-NASH trial, while Boehringer Ingelheim's Zealand Pharma-partnered survodutide has shown promising mid-stage results. For a detailed overview, see – Vital Signs: Tracking the MASH queue for GLP-1 agonists.