FDA Accepts FibroScan Letter of Intent for Surrogate Endpoint in MASH Trials

The US Food and Drug Administration (FDA)’s Center for Drug Evaluation and Research, Office of New Drugs has accepted Echosense’ Letter of Intent for the qualification of Liver Stiffness Measurement (LSM) by Vibration-Controlled Transient Elastography (VCTE; FibroScan) as a reasonably likely surrogate endpoint in clinical trials for metabolic dysfunction-associated steatohepatitis (MASH).1

According to a September 8, 2025, release from Echosens, this marks the first time the FDA is accepting the initiation of the qualification process of a non-invasive test as a reasonably likely surrogate endpoint in drug development for MASH. As stated in the Letter of Intent, which included official letters of support from Eli Lilly, Boehringer Ingelheim, and Novo Nordisk, LSM by VCTE can predict the risk of all-cause mortality or liver-related events in patients with MASH.1

"The acceptance of this Letter of Intent is a major milestone, built on years of clinical research and publications, together with the tireless efforts of numerous stakeholders across the field, with major implications for the field and is expected to accelerate drug development and also be easily translatable to clinical practice,” said Arun Sanyal, MD, professor and director at the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University.1

Acceptance of the Letter of Intent opens a path for FibroScan to ultimately replace liver biopsy as the primary endpoint for the interim analysis of trials designed for the accelerated approval of drugs for adults with noncirrhotic MASH.1

Currently, resmetirom (Rezdiffra) and semaglutide (Wegovy) are the only FDA-approved treatments for MASH, both with accelerated approvals in conjunction with diet and exercise.2,3 With several other agents in the pipeline progressing through clinical development, replacing liver biopsy with FibroScan could pose important implications for trial efficiency and safety.1

In a communication issued by the Agency, Frank Anania, MD, director of the Division of Hepatology and Nutrition in CDER, stated, "This proposal represents an important step toward adopting non-invasive tests in drug development for MASH."

Echosens asserts that replacing repeated liver biopsies, which are currently used to enroll patients and monitor therapeutic response, with FibroScan would ease a significant burden on patients because the exam takes just a few minutes, is painless, and assesses the liver comprehensively, providing a full picture of liver health that can be repeated as often as needed.1

FibroScan is supported by > 5600 peer-reviewed publications, including pivotal publications, showing changes in LSM by VCTE are associated with liver-related outcomes. Of note, FibroScan is already the reference point-of-care non-invasive test by all key pharma companies and biotechs conducting MASH trials.1

For pharmaceutical companies, the acceptance of FibroScan as a reasonably likely surrogate endpoint could have the potential to transform drug development in MASH by improving trial recruitment and patient retention, accelerating the path to new therapies while helping researchers design safer and more representative, efficient trials.1

"The FDA accepting this letter of intent is a critical first step to ultimately have non-invasive tests adopted as reasonably likely surrogate endpoints in MASH clinical trials,” said Quentin Anstee, Pro-Vice-Chancellor, Faculty of Medical Sciences at Newcastle University.1 “It's a clear signal to all pharma sponsors to collect robust non-invasive biomarker data in their ongoing or future clinical trials in MASH."

References

1. Echosens. FDA Accepts Letter of Intent to Qualify LSM by VCTE (FibroScan®) as First Non-Invasive Surrogate Endpoint in MASH Clinical Trials. September 8, 2025. Accessed September 9, 2025. https://www.prnewswire.com/news-releases/fda-accepts-letter-of-intent-to-qualify-lsm-by-vcte-fibroscan-as-first-non-invasive-surrogate-endpoint-in-mash-clinical-trials-302547998.html

2. Brooks A. Resmetirom (Rezdiffra) Receives Historic FDA Approval for Noncirrhotic NASH. HCPLive. March 14, 2024. Accessed September 9, 2025. https://www.hcplive.com/view/resmetirom-rezdiffra-receives-historic-fda-approval-for-noncirrhotic-nash

3. Brooks A. FDA Approves Semaglutide (Wegovy) Injection 2.4 mg for Noncirrhotic MASH. August 15, 2025. Accessed September 9, 2025. https://www.hcplive.com/view/fda-approves-semaglutide-wegovy-injection-2-4-mg-for-noncirrhotic-mash