Lead NASH contender falls short for FDA: Could NAFLD name change shift the status quo?

In the race for a first-to-market therapy for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, there have been multiple hopeful contenders; however, none have yet crossed the FDA finish line.

Last month, the FDA rejected the lead NASH drug contender, obeticholic acid, due to concerns that its risks outweigh its benefits. This action leaves Madrigal Pharmaceuticals’ resmetirom in a close second position for the treatment of non-cirrhotic NASH with liver fibrosis, with a decision expected sometime later this year.

Additionally, the potential for the term NAFLD to be changed still looms. The ongoing debate amongst the NAFLD Nomenclature Steering Committee continues as the nomenclature change may possibly deflate the stigma behind the term NAFLD due to the terms “fatty” and “alcoholic,” but could also set back decades of medical research and delay the development of new therapies.

Healio has been following the ongoing nomenclature debate as well as FDA news and research on health disparities in NASH and more. In case you have missed recent research, we have compiled a list of NASH and NAFLD articles to catch you up.

‘Unfavorable benefit-risk’: FDA panel votes against obeticholic acid approval for NASH

An FDA advisory committee voted against approval for obeticholic acid in pre-cirrhotic patients with liver fibrosis due to nonalcoholic steatohepatitis, citing a “concerning” benefit-risk profile.

The Gastrointestinal Drug Advisory Committee voted 12 to 2 with 2 abstentions that the benefits of 25 mg obeticholic acid (Ocaliva, Intercept Pharmaceuticals) do not outweigh its risks among patients with NASH and stage 2 or 3 fibrosis, most notably drug-induced liver injury and quality of life. Read more.

MAESTRO-NASH topline results: Resmetirom induces NASH resolution, fibrosis improvement

Topline findings from the phase 3 MAESTRO-NASH trial showed that resmetirom at both 100 mg and 80 mg doses improved resolution of nonalcoholic steatohepatitis without worsening fibrosis, Madrigal Pharmaceuticals announced.

This phase 3 data could place resmetirom, an oral thyroid hormone receptor-beta selective agonist, in a strong lead in the race among rival drug developers to develop the first pharmacotherapy approved for patients with NASH. Read more.

NAFLD ‘not fit for purpose’: Experts debate impact of changing name vs. definition

The term ‘non-alcoholic fatty liver disease’ no longer reflects current knowledge of the disease and should be changed, members of the NAFLD Nomenclature steering committee noted during The Liver Meeting.

“I think what was clear in the final round [of panel discussions] was a view that the current name is not fit for purpose,” committee co-chair Philip Newsome, MD, PhD, FRCPE, director of Research and Knowledge Transfer for the College of Medical & Dental Sciences at the University of Birmingham in the United Kingdom, told attendees. “The other thing that I think still needs to be developed is what a change in definition may or may not look like — and that is something we will explore in the next round.” Read more.

If not careful, NAFLD name change may damage decades of research on the disease

The term nonalcoholic fatty liver disease has been around for almost three decades and it is an imperfect term, because it uses two controversial words: “nonalcoholic” and “fatty”.

The words “fat” or “fatty” could be considered stigmatizing by patients. Additionally, the term “nonalcoholic” denotes absence of alcohol rather than presence of the underlying root cause of the disease: insulin resistance. These issues have caused some consternation. Although these are all legitimate concerns about the term NAFLD, there are several potential downsides of changing the name without a careful process of understanding the impact of the change. Read more.

New name for NAFLD may not be better, process may become ‘endless debate’

Many health care providers agree the term nonalcoholic fatty liver disease is a bad name because it’s defining a disease by what it is not; however, the challenge has been to find something that would fulfill a number of criteria.

Some patients feel that the term “nonalcoholic” gives them relief because when you tell someone they have cirrhosis, they link it to alcohol. It is difficult to find a term that will encompass the complexity of the disease, and changing the definition of NAFLD would make all prior studies invalid (ie, potentially a different population was studied under NAFLD). Read more.

Possible NAFLD name change must benefit both patients, field of hepatology

Regarding the nonalcoholic fatty liver disease nomenclature debate, I am pretty neutral to what the new name should be, and I want to be sensitive to all parties involved.

There are some people who are passionate about changing the name and others who feel it should not change. Whatever we decide to do, it must be helpful to our patients and to the hepatology field. Currently, the No. 1 need our patients have is treatment for nonalcoholic steatohepatitis-related fibrosis. Read more.

Q&A: ‘Heavy, heartfelt history’ of drug trials for Black patients may fuel NASH disparities

The Global Liver Institute has marked June 8 as International NASH Day, part of a public education campaign to raise awareness and urgency about fatty liver disease and its advanced form, nonalcoholic steatohepatitis.

According to the nonprofit organization, more than 115 million people worldwide are currently affected by NASH, and that number is expected to climb to 357 million people by 2030. This progressive form of nonalcoholic fatty liver disease is often underdiagnosed and underreported, with Black patients especially less likely to be diagnosed in early stages, despite facing worse outcomes, including mortality. Read more.

To focus solely on NAFLD nomenclature, not patient care, is ‘ultimately detrimental’

This exercise about nonalcoholic fatty liver disease nomenclature is a distraction from what patients really care about.

Patients are most interested in being correctly identified as having NAFLD or nonalcoholic steatohepatitis rather than being told they have just a little fatty liver and don’t worry about it. Patients are also interested in having a treatment approved, or, at least at this point, being cared for in a meaningful, engaged way with active monitoring and access to the tools we have — everything from a coach to a bariatric surgery consult, and many things in between, including weight loss medications and control of cholesterol and diabetes. Read more.

Quality of life, economic burden of NASH comparable, worse than type 2 diabetes

Patients with nonalcoholic steatohepatitis experienced similar mental and work-related impairment as patients with type 2 diabetes mellitus but worse physical status, daily activities impairment and more health care resource use.

“As a result of the possible asymptomatic presentation, low disease awareness, low rate of liver biopsy and no approved specific therapies, the prevalence and burden of NASH may be underestimated,” Elliot B. Tapper, MD, associate professor of gastroenterology and internal medicine at University of Michigan Health, and colleagues wrote in BMC Gastroenterology. Read more.