Novo, Viking Heat Up MASH Space with Promising Data at AASLD24

At the 75th The Liver Meeting of the American Association for the Study of Liver Diseases on Tuesday, Novo Nordisk and Viking Therapeutics presented strong data for their respective investigational therapies for metabolic dysfunction-associated steatohepatitis, touting significant improvements in liver fibrosis and marked reductions in liver fat.

Novo presented secondary endpoint results from the first part of the Phase III ESSENCE trial, which is testing its blockbuster GLP-1 receptor agonist semaglutide—sold as Ozempic for type 2 diabetes and Wegovy for chronic weight management—in MASH patients with moderate to advanced liver fibrosis.

At 72 weeks, 32.8% of patients on semaglutide achieved both resolution of steatohepatitis and improvements in liver fibrosis—more than twice the 16.2% rate in placebo comparators.

Semaglutide treatment also resulted in histological improvements at this time point, as measured by pre-specified noninvasive tests, versus placebo. Patients in the semaglutide arm also had better liver enzyme findings, including for alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase. Together, these three enzymes are indicative of overall liver function and health.

Earlier this month, Novo shared a headline readout from ESSENCE, revealing that 62.9% of patients treated with the GLP-1 analog hit hepatitis resolution without worsening of fibrosis at the 72-week follow-up, as compared with 34.1% of placebo counterparts. Meanwhile, 37% of semaglutide-treated patients saw fibrosis improvements with no deterioration in steatohepatitis status, versus 22.5% in the placebo arm.

BMO Capital Markets analyst Evan Seigerman wrote in a Tuesday note that Novo’s findings “stole the show” at AASLD 2024, with many meeting participants noting that the data represent “a watershed moment for the MASH field” and confirm that GLP-1 therapies hold strong therapeutic potential for MASH.

“Data presented from ESSENCE are supportive of semaglutide’s potential approval in MASH, potentially working to meaningfully expand payer coverage in select obese patient populations,” Seigerman noted, however adding that based on currently available data, efficacy seems to favor Eli Lilly’s tirzepatide “numerically,” though BMO will need to see more data from Lilly “to make an adequate comparison between the two assets.”

Novo is gearing up for an FDA filing for semaglutide in MASH in the first half of 2025, according to its Tuesday announcement.

Also at AASLD 2024, Viking Therapeutics unveiled Phase IIb data for its investigational selective thyroid hormone beta receptor agonist VK2809, touting its “best-in-class profile” for biopsy-confirmed MASH. At 52 weeks, Viking’s VOYAGE trial demonstrated a 37% to 55% mean reduction in liver fat. Response rate, defined as the percentage of participants reaching at least a 30% decrease in liver fat, ranged from 64% to 88% at this time point.

Viking in June 2024 released histological findings from VOYAGE, showing that up to 75% of patients treated with VK2809 reached MASH resolution without fibrosis worsening, while up to 57% showed at least a one-stage improvement in fibrosis without deterioration of MASH. Among placebo comparators, 29% and 34% hit these endpoints, respectively.

In his note on Tuesday, Seigerman called VK2809 “highly potent,” pointing out a “much higher response” in the subgroup of patients with F3 fibrosis treated with the lowest VK2809 dose—though this could potentially be due to an outlier effect driven by the study’s small sample size.

“All in we view Novo’s, Viking’s, and other data presentations we have seen this week as confirmatory of our view that GLP-1s will likely serve as backbone in this new age of MASH treatment,” Seigerman said, adding that this drug class could potentially be combined with other pathways—such as FGF21s and TGF-Bs—“potentially driving more rapid and deeper responses.”