Beth Snyder Bulik
Senior Editor
As fatty liver disease gets a new name, will it also finally get approved drug treatments?
That’s what healthcare professionals are hoping for as nonalcoholic fatty liver disease (NAFLD) becomes metabolic dysfunction-associated fatty liver disease (MAFLD), and nonalcoholic steatohepatitis (NASH) becomes metabolic dysfunction-associated steatohepatitis (MASH). The name changes, aimed at getting rid of stigmatizing language like “fatty liver,” are set to be fully rolled out later this year.
At the same time, physicians expect there will soon be a robust marketplace, with at least 10 potential drug candidates in clinical trials, according to a recent Spherix Global Insights physician survey. However, the pharmaceutical intervention they are most excited about is already widely used for other conditions.
Novo Nordisk’s semaglutide is the “most recognized and anticipated” drug for the treatment of NAFLD and NASH among survey respondents.
A majority of both gastroenterologists and hepatologists — ranging from 52% to 75% depending on their speciality areas and whether for NAFLD or NASH — said they would be “very likely” to prescribe semaglutide to patients if it’s approved for either condition in the future. Another 10% to 20% said they would be “moderately likely” to prescribe it.
There are currently no approved drugs for NAFLD or NASH, and typical treatment for both focuses on lifestyle changes to reduce weight and increase exercise, which have been proven to reduce fat in the liver. Even the 10 hopefuls are already down to nine after the FDA rejected Intercept’s obeticholic acid. Intercept then discontinued the program.
Physicians prefer semaglutide
The doctors who participated in the survey estimated that about two-thirds (65%) of their fatty liver disease patients have a comorbidity diagnosis of obesity. It’s not surprising that semaglutide, already approved to treat obesity as Wegovy, as well as type 2 diabetes as Ozempic, is spurring interest among the physicians. Even updated guidance from the American Association for the Study of Liver Diseases (AASLD) says “semaglutide can be considered for its approved indications (T2DM/obesity) in patients with NASH as it confers a cardiovascular benefit and improves NASH.”
The physicians agreed that one drawback to semaglutide is the lack of significant fibrosis improvement, a primary endpoint it failed in its NASH trial. However, Spherix analyst Geoff Red said that doesn’t mean they won’t use semaglutide — or other GLP-1s with similar weight loss benefits. Reducing overall body fat helps reduce fat in the liver, which helps it recover, he said. That means the weight loss drugs will likely play a role across all stages of the disease.
“The doctors are looking at all these new weight loss drugs and they’re saying, ‘This is what we need to help these patients,’” Red said. “As one of the doctors who put it best said, ‘I see these patients maybe four times a year for 15 or 20 minutes. There’s no way I’m going to change their behavior, but it needs to change. And they need help doing it.’”
Still, most of the doctors surveyed aren’t currently prescribing the medication to patients. Only a “small number” of the specialists in the survey said they are prescribing semaglutide off-label to NASH patients, Red said, given concerns around insurance coverage and scrutiny and the ongoing semaglutide shortages.
The surveyed specialists also said they preferred Madrigal Pharmaceuticals’ resmetirom, which completed its rolling submission NDA to the FDA last week, in addition to Inventiva Pharmaceuticals’ lanifibranor and Galmed Pharmaceuticals’ aramchol, which are both in Phase III studies.
Rethinking ‘stigmatizing language’
An estimated 25% of US adults live with NASH (whether they know it or not), according to the National Institutes of Health, and specialists are concerned about their capacity to treat so many people. They told Spherix researchers that their expertise is best used to treat the more serious NASH, while they expect primary care physicians to take on earlier NAFLD cases.
The NAFLD and NASH nomenclature changes are expected to get a measured rollout. Steatotic liver disease (SLD) will become the umbrella term for the conditions, and the newly added term MetALD will be used to describe people with NAFLD who also consume an increased amount of alcohol.
The medical groups decided on the name changes after a multi-year process to identify “an affirmative name and diagnosis without using stigmatizing language,” they said in a press release in June. The AASLD is currently working on a specific implementation plan for the rollout.
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