Novo Nordisks Semaglutide Delivers in Phase 3 MASH Study, Teeing Up Filings

Overview

With a positive readout for metabolic dysfunction-associated steatohepatitis (MASH) now in the bag, Novo Nordisk is gearing up to pursue yet another indication for its star GLP-1 medicine semaglutide.

The Phase 3 Essence Trial

• In the phase 3 Essence trial, a once-weekly dose of semaglutide 2.4 mg helped to improve liver fibrosis with no worsening of steatohepatitis and to resolve steatohepatitis with no worsening of liver fibrosis in patients with MASH who had stage 2 or stage 3 liver fibrosis. 
• Those results were sufficient for the trial to meet its primary endpoints, Novo Nordisk said in a Friday release.
• Digging deeper into the data, 37% of patients treated with semaglutide achieved improvement in liver fibrosis without their steatohepatitis worsening at the trial’s 72-week mark, compared to just 22.5% of patients on placebo.
• Further, 62.9% of patients on semaglutide saw their steatohepatitis resolved with no worsening of liver fibrosis, versus 34.1% of patients in the study’s control cohort.

Safety Profile of Drug

Semaglutide’s safety profile in Essence was generally on par with that in existing studies of the GLP-1 agonist, Novo said.

From the Novo Nordisk

• Given the positive readout, Novo said it expects to submit approval filings to regulators in the U.S. and Europe in the first half of 2025. 
• Detailed results from the company’s MASH study will be presented at an upcoming scientific conference this year, the drugmaker added.

Results from Par I & II: Essence Study

The results issued Friday came from part one of the Essence study. Part two is ongoing, with an expected readout to come in 2029, Novo said.

Related

Madrigal Maps out 'Way Forward' for MASH Patients in First Rezdiffra Campaign

• While MASH—which was previously known as nonalcoholic steatohepatitis, or NASH—has proven an elusive target, several drugmakers are starting to find increasing success in the metabolic liver disease. 
• In fact, Novo’s positive semaglutide readout comes just one day after Madrigal knocked Wall Street’s expectations out of the park with regards to third-quarter sales of its commercial MASH product Rezdiffra, which saw sales top out at $62 million for the earnings period.

Madrigal on III Quarter

In an analyst call Thursday, Madrigal said it closed out the third quarter with more than 6,800 patients on Rezdiffra, up from more than 2,000 at the start of the earnings period. 

From William Blair Analyst

From the perspective of William Blair analyst Andy Hsieh, Ph.D., Novo’s semaglutide readout is largely on par with the magnitude of fibrosis improvement shown by Rezdiffra, noting that the results have “practice-changing potential.”

Hsieh’s Team on Semaglutide

• Hsieh’s team said that investors are now rallying around the potential of GLP-1s like semaglutide in MASH, citing recent promising results from Eli Lilly’s tirzepatide and Boehringer Ingelheim’s survodutide (a dual GLP-1/glucan agonist) in the disease.
• We believe the consensus view within the investment community is that the GLP-1 receptor agonist class will likely be incorporated into the treatment paradigm for MASH,” Hsieh wrote in a note to clients Friday. “Today’s development adds to the growing body of evidence in support of that trend.
• In staking that claim, Hsieh noted that Viking Therapeutics is uniquely positioned in the field, thanks to the fact that the biotech is developing both a liver-directed candidate (VK2809) with the same mechanisms as Rezdiffra and a dual GLP-1/GIP agonist (VK2735) that shares its mode of action with Lilly’s tirzepatide.
• In our view, having both a liver-specific asset and a GLP-1-based dual agonist provides the company with multiple options, including combinatorial approaches, to address MASH,” Hsieh wrote.

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