[Edaily Reporter Minji Son ] Danish pharmaceutical company Novo Nordisk has launched a large-scale real-world data study using medical records from approximately 10,000 patients in South Korea with metabolic and fatty liver disease (MASLD) and metabolic and fatty liver steatohepatitis (MASH). As the company expands the scope of its obesity treatment Wegovy to include MASH, this move is seen as an effort to determine how accurately non-invasive test results predict long-term patient outcomes, such as cirrhosis and liver cancer.

According to the U.S. National Institutes of Health (NIH) clinical trial information site “ClinicalTrials.gov” on the 3rd, Novo Nordisk registered a real-world data study on the 31st of last month to analyze long-term clinical outcomes for MASLD and MASH patients.

The study began on the 13th of last month and is scheduled to conclude on September 30. It is a retrospective, multicenter observational study analyzing medical records of MASLD and MASH patients accumulated at domestic medical institutions. Unlike clinical trials that recruit new patients and administer drugs, this study utilizes existing medical data, resulting in a relatively short study period.

The study population consists of adult MASLD and MASH patients who underwent at least two liver stiffness measurements (LSM) using volumetric shear elastography (VCTE) at intervals of 1 to 5 years during routine clinical care. VCTE-LSM is a non-invasive test performed using a FibroScan device that measures the degree of liver fibrosis without the need for direct liver tissue sampling. Due to its advantages in terms of cost and convenience, it is widely used as a standard non-invasive test for liver fibrosis.

The research team analyzed how patients’ liver fibrosis risk groups changed between the first and second examinations. They examined whether events such as decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, or death occurred after the second examination to analyze the association between changes in risk groups and long-term clinical outcomes.

Novono Draws Attention for Non-Invasive Approach… Supporting Wigobi’s MASH Expansion

This study is not a clinical trial that evaluates the drug’s efficacy by directly administering Wigobi to patients. However

,

it is noteworthy in that it provides data supporting the clinical significance of non-invasive test markers immediately after Wigobi secured its

MASH

indication. As competition intensifies—with Eli Lilly’s “Mounjaro” capturing over half of the obesity treatment market—Novonordisk is expanding its business from obesity and diabetes into MASH, and this study is interpreted as an extension of that strategy.

Last August, Wegovy received accelerated approval from the U.S. Food and Drug Administration (FDA) as a treatment for MASH in patients with moderate-to-advanced liver fibrosis that has not progressed to cirrhosis. This approval was based on the interim results (Part 1) of Novo Nordisk’s global Phase 3 clinical trial, “ESSENCE.” Liver tissue examinations conducted after 72 weeks of treatment showed that the Wegovy group demonstrated statistically significant effects in resolving MASH and improving liver fibrosis compared to the placebo group.

However, it has not yet been definitively confirmed whether these improvements in biopsy results actually reduce the progression to cirrhosis or liver-related complications. To convert the accelerated approval to full approval, the ESSENCE trial must be extended to a total of 240 weeks, and Part 2 of the trial—to be completed by 2029—must confirm whether Wegovy reduces the progression to cirrhosis and liver-related clinical events.

Liver biopsy, which serves as the primary assessment tool in the MASH trial, is an invasive procedure requiring the direct collection of liver tissue. The procedure carries risks of pain and bleeding, and repeated biopsies place a significant burden on patients. Another limitation is the potential for results to vary depending on the biopsy site and the pathologist interpreting the sample.

Consequently, attention is focused on whether non-invasive diagnostic markers, such as VCTE-LSM, can complement or, in the long term, partially replace liver biopsies. Last August, the FDA also decided to review a proposal to develop LSM measured by VCTE as an alternative marker.

Novo Nordisk’s research in South Korea is also aligned with this trend. If an association is confirmed between changes in VCTE risk groups and cirrhosis, liver cancer, liver transplantation, and death based on the medical records of 10,000 South Korean patients, this will provide additional real-world evidence that non-invasive tests can estimate patients’ long-term risk.

The Spread of

Non-Invasive Markers… Opportunities vs. Burdens for Latecomers

The increasing reliability of non-invasive test

markers

is not a development that benefits only Novo Nordisk. This is because other companies developing MASH therapies can also utilize VCTE for patient selection, disease progression monitoring, and evaluation of treatment response.

If reliance on biopsies can be reduced, this would lessen the burden on clinical trial participants and streamline patient recruitment and follow-up. It could also help identify patients in need of treatment and monitor changes in their condition after treatment in real-world clinical settings.

In South Korea, Hanmi Pharmaceutical is conducting a Phase 2b clinical trial of its MASH candidate, eposepegtrutide. As a triple-acting agent that simultaneously activates GLP-1, glucagon, and GIP receptors, the trial is evaluating 215 MASH patients confirmed via biopsy to assess the resolution of steatohepatitis and the progression of fibrosis. The company plans to announce the results in the second half of this year.

If a relationship is confirmed between changes in VCTE risk groups and long-term clinical outcomes, it will broaden the foundation for latecomers—including Hanmi Pharmaceutical—to conduct research linking improvements in non-invasive test results to long-term prognosis.

On the other hand, some analysts suggest that with Wegovy having already secured the MASH indication, if real-world evidence linking non-invasive markers to long-term prognosis is accumulated, the bar for later-stage candidates could rise even higher. This means they will need to demonstrate clearer differentiation in terms of fibrosis improvement, ease of administration, and safety.

As mid- and late-stage clinical data for competing candidates have been accumulating recently, the securities industry has also begun to conservatively reflect the uncertainty surrounding Hanmi Pharmaceutical’s MASH pipeline. Seo Geun-hee, an analyst at Samsung Securities, stated, “We are revising the success rate of Hanmi Pharmaceutical’s MASH pipeline from 50% to 25%,” adding, “This adjustment reflects the delay in the announcement of clinical results for the MASH pipeline compared to initial expectations, as well as the rising standards for clinical efficacy resulting from the accumulation of late-stage clinical data from competing pipelines.”