FDA weighs noninvasive biopsy alternative in MASH clinical trials
Fibroscan uses sound waves to detect fibrosis
The U.S. Food and Drug Administration (FDA) will evaluate the use of Fibroscan, a noninvasive test, to replace liver biopsies in clinical trials for metabolic dysfunction-associated steatohepatitis (MASH), a progressive form of fatty liver disease.
The FDA’s Center for Drug Evaluation and Research (CEDR) accepted a proposal from Echosens, Fibroscan’s developer, to consider Fibroscan as a way to test potential trial participants and monitor patients during clinical trials. The company said the acceptance paves the way for Fibroscan to replace more invasive liver biopsies for patient recruitment and monitoring in MASH clinical trials.
“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,” Quentin Anstee, PhD, a hepatologist and professor at Newcastle University, said in a company press release.
A surrogate endpoint is a biomarker regulators believe can reasonably predict clinically meaningful patient outcomes, such as mortality or liver transplant, and serve as a stand-in to support a therapy’s conditional regulatory approval while long-term clinical outcome data are still being collected. The FDA’s decision is “a clear signal to all pharma sponsors to collect robust non-invasive biomarker data in their ongoing or future clinical trials in MASH,” Anstee said.
The FDA will review additional data to determine if Fibroscan can reliably predict clinically meaningful outcomes in people with MASH so that it can formally qualify as a reasonably likely surrogate trial endpoint.
‘Important step’ toward less painful tests
“This proposal represents an important step toward adopting non-invasive tests in drug development for MASH,” said Frank Anania, MD, director of the division of hepatology and nutrition at CDER.
MASH is an advanced stage of fatty liver disease in which fat accumulation in the liver gives rise to inflammation and fibrosis. Over time, this can lead to serious and irreversible liver damage.
Liver biopsies — where a small piece of liver tissue is collected and analyzed in a lab — are used in most MASH clinical trials to identify eligible participants and monitor treatment responses. Changes in fibrosis and other disease markers in the tissue sample reflect how well an experimental treatment is working to stabilize or reverse the liver disease.
However, these biopsies require repeated painful, invasive, and costly procedures, and there has been a push to move away from liver biopsies and toward fewer invasive monitoring tools.
Fibroscan, which is being used in some MASH clinical trials, uses ultrasound waves to determine the liver’s stiffness. A stiffer liver generally means more liver fibrosis.
The test allows doctors to make a comprehensive assessment of liver health within minutes. It is painless and can be repeated as often as needed. Echosens expects this will substantially reduce patient burden and make clinical trial enrollment and monitoring easier.
The goal of the qualification process with the FDA is to have Fibroscan established as a reasonably likely surrogate endpoint in MASH trials. Echosens says this is supported by thousands of publications showing that changes in liver stiffness, as assessed by Fibroscan, correlate with clinical outcomes in MASH. The test can, according to the company, predict the risk of death and liver-related events.
The submission to the FDA included official letters of support from pharmaceutical companies, including Eli Lilly, Boehringer Ingelheim, and Novo Nordisk. “Prominent guidelines” also recommend Fibroscan, and insurance provider policies prefer its use, Echosens noted.
“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,” said Arun Sanyal, MD, director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University. It has “major implications” in the MASH field and is “expected to accelerate drug development and … be easily translatable to clinical practice,” Sanyal said.
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