Novo to Pursue Endorsement for Obesity Medication Based on Recent Findings in MASH
On Friday, Novo Nordisk announced its intention to pursue regulatory approval for semaglutide, an active component in its acclaimed weight loss medication, targeting a prevalent liver ailment after encouraging outcomes from a Phase 3 trial.
Initial findings shared in a press release indicate that semaglutide achieved both primary endpoints in the preliminary segment of a late-stage, placebo-controlled investigation involving individuals with metabolic dysfunction-associated steatohepatitis, abbreviated as MASH. Specifically, after 72 weeks of monitoring, 37% of participants administered semaglutide alongside standard treatment exhibited improvements in liver scarring without any deterioration in their condition, compared to 22.5% among those who received a placebo with usual care. Furthermore, 63% of patients on semaglutide experienced a resolution of MASH without any worsening of scarring, while only 34% of those on the placebo did so.
Novo reported that semaglutide exhibited a “safe and well-tolerated profile,” aligning with observations from prior studies.
However, Novo did not elaborate on further study specifics, leaving uncertainties regarding semaglutide’s performance on various secondary endpoints or the number of participants who may have discontinued treatment due to adverse reactions. Comprehensive results are expected during an upcoming medical conference in 2024. The second phase of the trial is also set to continue for several years to evaluate semaglutide’s efficacy in preventing cirrhosis, a frequent complication of MASH.
These favorable results position semaglutide as a contender to potentially be the first medication approved for MASH, a liver condition estimated to impact millions and recognized as one of the leading causes for liver transplants. Novo plans to pursue approvals for semaglutide in MASH within the U.S. and Europe during the first half of 2025.
“We are thrilled with the findings from the ESSENCE clinical trial and the promise of semaglutide in assisting individuals coping with MASH,” stated Martin Holst Lange, Novo’s head of development, referencing the Phase 3 trial’s designation. “Among the overweight or obese population, one in three is affected by MASH. This condition significantly compromises their health and reveals a profound unmet medical need.”
MASH arises due to a harmful buildup of fat in the liver and generally coincides with other metabolic disorders such as diabetes. Despite being historically targeted by pharmaceutical companies, it has posed significant challenges. Several notable therapies have not succeeded in clinical trials, and the first application to U.S. regulators—a treatment from Intercept Pharmaceuticals—was denied in 2023.
Recent developments include a newer category of medications, with Madrigal Pharmaceuticals’ Rezdiffra receiving approval in March, marking it as the first authorized drug for this condition, which has since been successfully launched. Additional therapies from Akero Therapeutics and 89bio have also demonstrated potential, although their trial outcomes remain less definitive.
GLP-1 medications, such as semaglutide, are being recognized for their potential in treating MASH. These drugs influence gut hormones and have demonstrated remarkable effects on weight management, cardiovascular health, and more, with MASH being perceived as a new opportunity for them. Meanwhile, Eli Lilly and collaborators Boehringer Ingelheim and Zealand Pharma have already showcased favorable results in Phase 2 trials, igniting investor enthusiasm regarding the possibility of GLP-1 medications transforming MASH treatment.
Nonetheless, some Wall Street analysts remain unconvinced about this development. On Friday, multiple analysts emphasized that the results do not distinctly set semaglutide apart from alternative MASH treatments, allowing room for competition. The findings affirm that GLP-1 medications have “utility” in addressing certain aspects of MASH but do not present a definitive solution, as noted by Leerink Partners’ Thomas Smith.
Those evaluating the degree of semaglutide’s effects on liver fibrosis found its placebo-adjusted efficacy to be “similar” to that of Rezdiffra, as remarked by William Blair analyst Andy Hsieh. RBC Capital Markets’ Brian Abrahams observed that the effect size for semaglutide was less pronounced than what has been reported with 89bio and Akero’s therapies, albeit acknowledging the complexity of comparing medications across different trials.
“We believe that this outcome eliminates a potential adverse scenario where semaglutide exhibited transformative improvement in fibrosis,” stated Leerink’s Smith, anticipating that MASH may become a landscape for multiple treatment avenues and mechanisms.
Following the news, Madrigal’s stock surged nearly 15% in early trading. Shares for both 89bio and Akero also witnessed gains amid the trading session.