Hepatology Year in Review: 2024

HCPLive 2024 Hepatology Year in Review

2024 was nothing short of historic for the field of hepatology, characterized by groundbreaking regulatory decisions, pivotal clinical advancements, and significant strides in understanding liver disease.

From the US Food and Drug Administration (FDA) approval of the first-ever metabolic dysfunction-associated steatohepatitis (MASH) drug to its rejection of a long-standing second-line therapy for primary biliary cholangitis (PBC), the past year has seen several notable FDA decisions sure to leave a lasting impact on hepatic care.

Beyond regulatory approvals, and in some cases, a lack thereof, 2024 also saw new hepatitis B virus (HBV) guidelines from the World Health Organization as well as new clinical trial data for novel agents in MASH and alcohol-associated hepatitis.

This hepatology year in review spotlights HCPLive’s coverage of the top hepatic news and research from 2024!

Resmetirom (Rezdiffra) Receives Historic FDA Approval for Noncirrhotic NASH

In a landmark decision for the field of hepatology, the FDA granted accelerated approval to resmetirom (Rezdiffra) for the treatment of adult patients with noncirrhotic nonalcoholic steatohepatitis (NASH), now known as MASH, with moderate to advanced fibrosis, making it the first and only treatment to receive approval for the progressive liver disease.

Announced on March 14, 2024, the decision followed 18 clinical studies in the oral, thyroid hormone receptor (THR)-β selective agonist’s clinical development program: 12 phase 1 studies, a pair of phase 2 studies, and 4 phase 3 studies. Of note, resmetirom’s approval is conditional, with continued approval for this indication contingent upon verification and description of clinical benefit in ongoing confirmatory trials.

Related Series: Understanding NASH/NAFLD vs MASH/MASLD

ESSENCE: Semaglutide Improves Fibrosis, Resolves Steatohepatitis in MASH

Although resmetirom was the first agent to earn FDA approval for the treatment of MASH, phase 3 data for Novo Nordisk’s semaglutide indicate the GLP-1 RA may not be far behind. Headline results from the first part of the ongoing ESSENCE study of once-weekly subcutaneous semaglutide 2.4 mg in adults with MASH with moderate to advanced fibrosis showed the trial achieved its primary endpoints for statistically significant and superior improvement in liver fibrosis with no worsening of steatohepatitis as well as resolution of steatohepatitis with no worsening of liver fibrosis.

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

This year, the first point-of-care hepatitis C virus (HCV) test was made available with the FDA’s marketing authorization of Cepheid for the Xpert HCV test and GeneXpert Xpress System. Intended for adults at risk of or with signs or symptoms of HCV, the test detects HCV RNA and provides results in about an hour using a blood sample from the fingertip and can be performed in settings operating under a Clinical Laboratory Improvement Amendments (CLIA) Certificate of Waiver, such as certain substance use disorder treatment facilities; correctional facilities; syringe service programs; doctor’s offices; emergency departments; and urgent care clinics.

FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC

The US Food and Drug Administration granted accelerated approval to elafibranor (Iqirvo) 80 mg tablets for the treatment of PBC in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA.

Announced on June 10, 2024, the decision was based on a reduction of alkaline phosphatase (ALP) observed in the multi-center, 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. Full results presented at the American Association for the Study of Liver Disease (AASLD) meeting in 2023 showed treatment with the dual peroxisome-activated receptor (PPAR) alpha/delta agonist resulted in statistically significant improvements in biomarkers of disease progression across key endpoints with a significant treatment benefit achieved in the primary composite endpoint for biochemical response.

FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis

Just 2 months after the FDA granted accelerated approval to elafibranor, the agency conditionally approved seladelpar (Livdelzi) for the same indication based on data from the phase 3 RESPONSE study, which showed 62% of patients treated with seladelpar achieved the primary endpoint of composite biochemical response at month 12 versus 20% of patients taking placebo.

Like elafibranor, the oral, selective PPAR delta agonist’s accelerated approval was based on a reduction of ALP, and improvement in survival or prevention of liver decompensation events had not been demonstrated at the time of this decision. The continued approval of both second-line agents is contingent upon verification and description of clinical benefit in confirmatory trial(s).

Related Series: Shifting Treatment Goals, Timelines in Primary Biliary Cholangitis

FDA Issues CRL to Obeticholic Acid (Ocaliva), Denies Full Approval for PBC

While the PBC treatment landscape greatly expanded in 2024 with the addition of 2 new second-line therapies, it also saw the loss of obeticholic acid (Ocaliva), which was the sole FDA-approved second-line agent for PBC for nearly a decade.

In a November 12, 2024, Complete Response Letter, the FDA said it was unable to approve Intercept Pharmaceuticals’ supplemental New Drug Application in its current form, consistent with the outcome of a Gastrointestinal Drugs Advisory Committee meeting held in September 2024 that yielded a negative opinion on the verification of obeticholic acid’s benefit on clinical outcomes in PBC as well as its benefit versus risk profile.

Related: Nancy Reau, MD: Obeticholic Acid’s Future in PBC After FDA Advisory Committee Meeting

Related: FDA Finds Obeticholic Acid (Ocaliva) Linked to Serious Liver Injury in Noncirrhotic PBC

FDA Approval of Maralixibat for Cholestatic Pruritus in PFIC Signals New Frontier for IBAT Inhibitor

The FDA approved maralixibat (Livmarli) oral solution for the treatment of cholestatic pruritus in patients 5 years or older with progressive familial intrahepatic cholestasis (PFIC). The decision marked the ileal bile acid transporter (IBAT) inhibitor’s second rare liver disease indication, the first being for the treatment of cholestatic pruritus in patients with Alagille syndrome ≥ 3 months of age.

Related: FDA Approves Label Expansion for Maralixibat (Livmarli) in PFIC

WHO Releases New Hepatitis B Guidelines

In addition to the plethora of hepatic FDA news, 2024 also saw new hepatitis B guidelines from the World Health Organization in an update to the previously published 2015 guidelines. Focused on the prevention, diagnosis, care, and treatment of hepatitis B virus, the guidelines make evidence-based recommendations reflecting updated data on antiviral effectiveness, diagnostic performance of tests, and service delivery models.

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

Although alcohol-associated hepatitis care has long relied on abstinence and adequate nutritional support in the absence of an FDA-approved therapeutic, findings from the phase 2b AHFIRM trial suggest a pharmacologic agent may be on the way to aid disease management for these patients.

Data highlight the endogenous sulfated oxysterol’s impact on 90-day mortality and liver transplantation, especially among US-based trial participants. While the trial did not meet its primary endpoint for 90-day mortality or liver transplant in the global study population, statistical significance was reached in analyses focusing solely on participants from the US, who comprised 75% of the total study population.