Efinopegdutide

Despite touting the results of a mid-stage metabolic dysfunction-associated steatohepatitis (MASH) trial as a success, Altimmune's stock plummeted on Thursday, shaving more than 53% off its valuation. While its dual GLP-1/glucagon receptor agonist pemvidutide hit one of the study's co-primary endpoints, it fell short on the second — after reassuring investors earlier that it was on track to meet both measures.The Phase IIb IMPACT trial randomised 212 patients with biopsy-confirmed MASH and fibrosis stages F2/F3 with and without diabetes to receive either a 1.2 mg or 1.8 mg weekly subcutaneous dose of pemvidutide, or placebo After 24 weeks, 59.1% and 52.1% of those taking the low and high doses, respectively, achieved MASH resolution without worsening of fibrosis based on an intent-to-treat (ITT) analysis, which considered missing biopsies as non-responders. The results were statistically significant compared with the placebo arm, which had a 19.1% achievement rate.For the second measure, 31.8% and 34.5% of patients who received 1.2 mg and 1.8 mg pemvidutide, respectively, saw an improvement in fibrosis without worsening of MASH, which was not significant versus the 25.9% rate seen with placebo. Despite the miss, Altimmune said that when it conducted a supplemental AI-based analysis, the high dose demonstrated statistically significant reductions in fibrosis, with 30.6% of patients in that group achieving a 60% or more reduction in fibrosis compared to 8.2% for placebo.The company's AI argument didn't seem to convince investors, however, who had high expectations going into the readout. According to a note shared earlier by Jefferies, Altimmune's management had said during a fireside chat that it expected to hit statistical significance on all critical endpoints, including fibrosis and MASH improvements, and weight loss. Pemvidutide did meet the statistical significance threshold for weight loss — patients receiving the low and high doses lost 5% and 6.2% of their bodyweight, respectively, versus 1% for placebo — but the miss on fibrosis seemed to be the driving factor behind the company's stock drop. B. Riley analysts said that following a virtual non-deal roadshow with Altimmune, it "came away particularly bullish" on the IMPACT readout, predicting that pemvidutide could become a "one-stop solution for addressing the severe liver disease comorbidity associated with obesity by delivering on best-in-indication fibrosis improvement."They also noted that for Altimmune's incretin to be differentiated from other GLP-1s being evaluated for MASH, such as Novo Nordisk's semaglutide, Eli Lilly's tirzepatide, and Boehring Ingelheim's survodutide, a statistically significant fibrosis improvement at week 24 would be key. For further analysis, see Vital Signs: Tracking the MASH queue for GLP-1 agonists.Another area in which pemvidutide could stand out from the incretin crowd is tolerability. Altimmune reported that no patients receiving the low dose discontinued treatment due to adverse events (AEs), with a rate of 1.2% for those in the high dose group, compared with 2.4% for the placebo arm. There were no treatment-related serious AEs.

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.