Hepatology Month in Review: June 2024

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This June 2024 month in review highlights hepatic pipeline developments, new MASH therapeutics on the road to FDA approval, and the latest installment of Qazi Corner.

With the first half of 2024 coming to a close, June built upon the excitement from months past and was a fitting conclusion to the first 6 months of a year that will go down in history for the field of hepatology. Our June 2024 month in review spotlights some of the top hepatic news and research from the past few weeks, including US Food and Drug Administration (FDA) news, pipeline developments, metabolic dysfunction-associated steatohepatitis (MASH) therapeutics on the horizon, and the latest installment of Qazi Corner.

Pipeline News

FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC

June was a busy month for the hepatic pipeline, but no development surpassed that of elafibranor (Iqirvo) for PBC, which earned accelerated approval on June 10 for use in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA. The decision was based on reduction of alkaline phosphatase (ALP) in the multicenter, randomized, double-blind, placebo-controlled phase 3 ELATIVE trial evaluating the efficacy and safety of elafibranor 80 mg once daily versus placebo for the treatment of patients with PBC with an inadequate response or intolerance to UDCA. Continued approval is contingent upon verification and description of clinical benefit in confirmatory trial(s), specifically regarding improvement in survival and prevention of liver decompensation events.

AHFIRM: Phase 2b Data Shows Promise for Larsucosterol in Alcohol-Associated Hepatitis

New phase 2b data from the AHFIRM trial are providing hepatologists and patients alike with hope that a novel therapeutic for alcohol-associated hepatitis may be on its way. Larsucosterol, an endogenous sulfated oxysterol, was granted Breakthrough Therapy designation by the FDA for patients with severe alcohol-associated hepatitis on May 21, 2024, and additional findings from AHFIRM were presented shortly thereafter at the European Association for the Study of the Liver (EASL) Congress.

FDA Grants Marketing Authorization to Xpert HCV, First Point-of-Care Hepatitis C RNA Test

Finishing the month just as strong as it began, June’s final hepatic pipeline development came in the form of Cepheid’s receipt of a marketing authorization from the FDA for the Xpert HCV test and GeneXpert Xpress System, the first point-of-care HCV test allowing for a more rapid test-and-treat approach compared to the standard multi-step HCV testing process. The test, intended for adults at risk of or with signs or symptoms of HCV, may be performed in settings operating under a Clinical Laboratory Improvement Amendments Certificate of Waiver and provides results in about an hour using a blood sample from the fingertip.

“Despite the existence of a safe and highly effective oral cure for hepatitis C, many people do not know they have the disease due partly to the lack of availability of convenient, widespread testing options,” Jeff Shuren, MD, JD, director of the FDA’s Center for Devices and Radiological Health, said in a press release. “Equipping health care providers with tools to diagnose and treat patients in the same visit can result in hundreds of thousands more hepatitis C patients being diagnosed and treated, preventing individual disease progression and additional spread of the virus.”

Updates in MASH

Naim Alkhouri, MD: Resmetirom Has Been a “Game Changer” in MASH Since FDA Approval

Resmetirom (Rezdiffra) fundamentally reshaped the MASH treatment landscape when it became the first FDA-approved therapeutic for the progressive liver disease in March. Now, 3 months after this landmark decision, Naim Alkhouri, MD, chief medical officer, chief of transplant hepatology, and director of the Fatty Liver Program at Arizona Liver Health, continues to emphasize how resmetirom has been a “game changer” in MASH care.

Survodutide Improves MASH Without Worsening of Fibrosis, Reduces Liver Fat

Although resmetirom was the first MASH therapeutic to cross the FDA finish line and achieve the highly sought-after stamp of approval, other agents are following closely behind. Phase 2 data for survodutide, a dual glucagon and glucagon-like peptide-1 (GLP-1) receptor agonist, reinforce its potential to eventually join resmetirom on the list of FDA-approved MASH therapeutics, demonstrating its ability to improve MASH without worsening fibrosis.

“I am particularly excited about the findings of the Phase II trial in survodutide, which demonstrate the potential for glucagon agonism, in addition to GLP-1, to both improve MASH and shift the needle on fibrosis,” said principal investigator Arun Sanyal, MD, professor of Medicine, Physiology and Molecular Pathology at Virginia Commonwealth University School of Medicine. “These data position survodutide as a leading glucagon/GLP-1 receptor dual agonist that could be a game-changer for people living with MASH and clinically significant fibrosis.”

SYNERGY-NASH: Tirzepatide, a GIP/GLP-1 RA, Resolves MASH Without Worsening Fibrosis

Another agent progressing through the MASH pipeline, tirzepatide, showed equally promising phase 2 data with statistically significant improvements in MASH without worsening fibrosis in patients with MASH and moderate to severe fibrosis. A glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist, tirzepatide was superior to placebo at 52 weeks across both measures of MASH improvement and no worsening of fibrosis.

Qazi Corner

Bariatric Surgery in Patients Hospitalized with Decompensated Cirrhosis: A Nationwide Analysis

June also saw the publication of the sixth installment of Qazi Corner, a collaborative quarterly newsletter on gastroenterology research, news, and trends between HCPLive and editor-in-chief Taha Qazi, MD, a gastroenterologist at Cleveland Clinic. This edition featured a retrospective, population-based analysis using data from the National Inpatient Sample database to determine the effect of bariatric surgery on outcomes of cirrhosis decompensation events. Penned by Stephen Firkins, MD, the article described improved outcomes among patients with obesity and a history of bariatric surgery hospitalized with decompensated cirrhosis compared to nonsurgical patients, alluding to overall improved metabolic and comorbid health conferred by bariatric surgery.