Rezdiffra marks a groundbreaking milestone as the inaugural drug sanctioned for the treatment of scarring due to hepatic fat accumulation, a consequence often associated with obesity. This medication, also known as resmetirom, serves to mitigate the detrimental effects of nonalcoholic steatohepatitis (NASH), a condition with the potential to culminate in liver failure.
In a significant development, the U.S. Food and Drug Administration (FDA) has granted approval to the initial pharmaceutical intervention for the prevalent liver ailment recognized as nonalcoholic steatohepatitis, or fatty liver disease.
Regulatory authorities have authorized the introduction of Rezdiffra, a once-daily oral medication (resmetirom), designed for adults afflicted with NASH — specifically, noncirrhotic nonalcoholic steatohepatitis — who exhibit moderate to advanced levels of liver scarring, medically termed fibrosis. The FDA underscored the importance of pairing this medication with dietary adjustments and physical activity, as stated in an official announcement.
NASH, also referred to as metabolic dysfunction-associated steatohepatitis (MASH), emerges due to an accumulation of fat in the liver, a phenomenon commonly observed in individuals grappling with overweight or obesity.
This condition represents an advanced manifestation of nonalcoholic fatty liver disease (NAFLD), wherein lipid deposition within the liver initiates a cascade of inflammation and tissue damage, ultimately leading to fibrosis. If left unchecked, NASH can progress to cirrhosis, or an advanced stage of liver disease that may necessitate a liver transplant for treatment.
“Previously, patients with NASH who also have notable liver scarring did not have a medication that could directly address their liver damage,” said Nikolay Nikolov, MD, in a statement. He is the acting director of the Office of Immunology and Inflammation in the FDA’s Center for Drug Evaluation and Research. “Today’s approval of Rezdiffra will, for the first time, provide a treatment option for these patients, in addition to diet and exercise.”
“Approval of resmetirom is an incredibly exciting development in the management of NASH, the most common liver disease in the world,” Suzanne Sharpton, MD, an assistant professor and transplant hepatologist at Vanderbilt University Medical Center in Nashville, Tennessee, also shared.
“Drug development in NASH has been very challenging to date,” Dr. Sharpton added. “This is the first treatment with effects on steatohepatitis as well as fibrosis — which is clinically meaningful, particularly as fibrosis stage is associated with [complications] in people with NASH.”
Where New Meds Fit with General NASH Management
At first, NASH could be addressed through lifestyle adjustments aimed at weight reduction, like adopting a low-calorie diet or stepping up physical activity, combined with medication. This approach may involve cutting down or quitting alcohol consumption, as well as using medication to control concurrent health conditions such as type 2 diabetes or high cholesterol.
Sharpton highlighted that Resmetirom might offer assistance to individuals encountering difficulties in implementing impactful lifestyle modifications.
“Developing new treatments for NASH is imperative due to the limited effectiveness of existing medicines in halting or reversing the disease’s progression,” said Amir Ansaripour, PhD, PharmD. He is the associate director of health economics and outcomes research at Optimax Access in the United Kingdom and he has studied resmetirom.
“Pharmacologic treatments are sorely needed, as there is no other FDA-approved pharmacologic therapy,” Sharpton said. “Our current management focus is on lifestyle modification including diet and exercise with an overall goal to lose weight, which is challenging to achieve and sustain for many patients.”
Resmetirom Showed Impressive Trial Results, Particularly for NASH
In a pivotal late-phase clinical trial documented in The New England Journal of Medicine, researchers randomly assigned 966 individuals with nonalcoholic steatohepatitis (NASH), all of whom had fibrosis that hadn’t yet progressed to cirrhosis, to receive either an 80 milligram (mg) or 100 mg resmetirom pill or a placebo pill daily for one year.
At the conclusion of the study period, it was observed that 30 percent of patients administered the higher dosage of resmetirom experienced a reduction of NASH severity by at least two points on an 8-point scale, alongside no worsening of fibrosis. This was in contrast to approximately 10 percent of those in the placebo group. Furthermore, fibrosis showed significant improvement in 26 percent of patients on the 100 mg dosage and 24 percent of those on the 80 mg dosage, compared to 14 percent in the placebo group.
“Effectively, resmetirom may not only prevent the progression but also reverse the fibrosis,” said Jean-François Dufour, MD. He is a researcher at the Centre Digestive for Diseases in Lausanne, Switzerland. He was not part of the said study but he has research about NASH and resmetirom.
Resmetirom exhibited a higher incidence of diarrhea and nausea compared to the placebo, yet the occurrence of severe side effects was infrequent and consistent among all three intervention groups.
“Resmetiron is safe and reduces liver fibrosis — it’s the only one that does this,” Mary Rinella, MD, a professor and transplant hepatologist at the Pritzker School of Medicine at the University of Chicago and the coauthor on the study, said.
Due to this, physicians might initiate screenings for individuals at high risk of NASH and fibrosis earlier, aiming to intervene and impede fibrosis progression before severe and irreversible liver damage ensues, according to Dr. Ansaripour.
“The availability of resmetirom as a treatment for NASH has the potential to significantly change treatment guidelines and the overall approach to managing the disease,” Ansaripour said.
“Resmetirom could trigger revisions in guidelines, encouraging primary care screening for NASH in high-risk patients and potentially changing the timing and progression of fibrosis treatment,” Ansaripour added. “This could lead to a proactive shift towards preventing disease progression, emphasizing early intervention, and promoting collaboration among healthcare providers for a multidisciplinary approach.”
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