Hepatology Month in Review: February 2024

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Our February 2024 month in review highlights some of our top hepatology content from the past few weeks, including pipeline updates, phase 2/3 trial data, and new research in liver diseases.

Much like January, February proved to be a pivotal month in the field of hepatology, providing further evidence to support the notion that 2024 is going to be a crucial year. With plenty of action in the pipeline through the first 2 months of the year and much more expected in months to come, it is likely that 2024 will see unprecedented progress in the way hepatologists understand and are able to treat liver disease. Our February 2024 month in review spotlights some of our top coverage of pipeline updates, clinical trial data, and new research about disparities and stigma in hepatic diseases.

Hepatology Pipeline News

FDA Grants 510(k) Clearance to Liver Attenuation AI Software HealthFLD

On February 13, the US Food and Drug Administration (FDA) granted 510(k) clearance to Nanox’s HealthFLD, an artificial intelligence software that provides automated qualitative and quantitative analyses of liver attenuation from routine contrast and non-contrast chest and abdomen CT scans in patients 18-75 years of age. Integrating HealthFLD with widely used standard CT scans may offer a potential solution to the growing prevalence of liver-related diseases, allowing clinicians to opportunistically screen for liver steatosis and possible signs of metabolic dysfunction-associated steatotic liver disease (MASLD) on a population level.

FDA Grants Fast Track Designation for Bepirovirsen for Chronic Hepatitis B

In another piece of pipeline news released on February 13, the FDA granted Fast Track designation to GSK’s bepirovirsen for the treatment of chronic hepatitis B based on its potential to address an unmet medical need given the low functional cure rates in currently available treatments. A triple-action investigational antisense oligonucleotide, bepirovirsen is the only agent in phase 3 development that has shown the potential to achieve clinically meaningful functional cure response when combined with oral nucleoside/nucleotide analogs. The Fast Track application was supported by data from the phase 2b trials B-Clear and B-Sure, which evaluated the efficacy, safety, and durability of response of bepirovirsen in people with chronic hepatitis B.

Clinical Trial Data, Treatments In The Pipeline

Survodutide, a Glucagon/GLP-1 RA, Reduces MASH in Phase 2 Trial

Early but promising data suggest survodutide may help improve metabolic dysfunction-associated steatohepatitis (MASH) without worsening fibrosis. The glucagon/GLP-1 receptor dual agonist is being examined in 5 phase 3 trials among people with overweight and obesity. In the phase 2 trial, use of survodutide was associated with statistically significant improvement in MASH, with 83% of the survodutide arm achieving histological remission compared to 18.2% of the placebo arm (response difference, 64.8%; CI, 51.1-78.6; P <.0001).

RESPONSE: Seladelpar Normalizes Alkaline Phosphatase, Reduces Pruritus in PBC

Data from the phase 3 RESPONSE trial of seladelpar in patients with primary biliary cholangitis (PBC) and incomplete response or intolerance to ursodeoxycholic acid showed treatment with the peroxisome proliferator-activated receptor delta (PPARδ) agonist elicited biochemical response while also reducing pruritus. Seladelpar releases fibroblast growth factor 21 from hepatocytes, reducing the accumulation of bile acids by inhibiting the expression of cholesterol 7α-hydroxylase and also decreasing proinflammatory macrophages.

Results showed a greater percentage of the patients in the seladelpar group elicited a biochemical response (61.7%) compared to those in the placebo group (20.0%; difference, 41.7 percentage points; 95% CI, 27.7-53.4; P <.001), with findings generally consistent among patients with and without cirrhosis and among patients who received seladelpar alone versus those who received seladelpar with ursodeoxycholic acid.

Stephen Harrison, MD: Promising Phase 3 Data for Resmetirom in NASH, Fibrosis

Another treatment in the pipeline for liver disease, data from the phase 3 MAESTRO-NASH trial of resmetirom in patients with NASH and fibrosis suggest the thyroid hormone receptor-β selective agonist may be poised to become the first approved treatment for the progressive liver disease. Designed to target key underlying causes of NASH in the liver, resmetirom’s safety and efficacy for adults with NASH have been demonstrated in phase 2 and 3 trials.

MAESTRO-NASH, a phase 3, double-blind, randomized, placebo-controlled trial, is 1 of 18 studies in resmetirom’s clinical development program supporting the NDA for its use in adult patients with NASH and fibrosis. Results showed a greater proportion of patients in the resmetirom 80 mg and 100 mg treatment arms achieved NASH resolution with no worsening of fibrosis as well as fibrosis improvement by ≥ 1 stage with no worsening of the nonalcoholic fatty liver disease (NAFLD) activity score compared to those receiving placebo.

Stigma, Disparities in Hepatic Diseases

Providers May Be Overlooking Average-Risk Patients for HCV Screening

Findings from a recent cross-sectional survey suggest providers may still be basing their hepatitis C virus (HCV) screening recommendations on patient risk factors and overlooking screening in patients perceived to be at average risk of infection, going against the US Preventive Services Task Force’s recommendation for universal HCV screening for all individuals 18-79 years of age. Among 284 primary care providers in Indiana, 42.4% reported strongly recommending HCV screening to patients who did not present risk factors compared to 70.4% for high-risk patients, with results also showing the strength, frequency, and timeliness of screening recommendations were lower for average-risk patients compared to their high-risk counterparts.

The Power of Words: Liver Transplant Centers Continue to Use Stigmatizing Language

A cross-sectional review found language considered to be stigmatizing was prevalent across 88% of transplant center websites and 46% of addiction psychiatry websites from the same institutions, despite practice recommendations from several medical societies advising against potentially stigmatizing language for alcohol use disorder (AUD) and alcohol-associated liver disease (ALD).

Related: ‘There’s Still A Long Way To Go’: Wei Zhang, MD, PhD, on Stigmatizing Language in Liver Transplant Centers