Q1 2025 Recap: Hepatology News and Updates

The first quarter of 2025 brought significant advancements in hepatology, from regulatory milestones to groundbreaking clinical trial data and new clinical guidance.

The US Food and Drug Administration (FDA) granted key designations to potential therapies for primary biliary cholangitis (PBC), chronic hepatitis delta, and primary sclerosing cholangitis (PSC), signaling progress in addressing historically challenging liver diseases. Meanwhile, clinical trial data offered new hope, with efruxifermin demonstrating the ability to reverse metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis and zetomipzomib showing promise for autoimmune hepatitis.

The quarter also saw the release of new guidelines on hepatitis B reactivation and early biliary atresia detection. Rounding out Q1 was the 1-year anniversary of resmetirom’s FDA approval for MASH, explored in a special 6-part HCPLive RX Review.

The recap offers a look back at the top developments in hepatology from the first 3 months of 2025:

Regulatory Updates

FDA Grants Orphan Drug Designation to CNP-104 for Primary Biliary Cholangitis

Starting the year on a high note, on January 8, 2025, COUR Pharmaceuticals announced the FDA granted Orphan Drug Designation to CNP-104 for the treatment of PBC.

“Receiving Orphan Drug Designation for CNP-104 underscores its potential to become the first disease-modifying treatment for individuals with PBC,” said Dannielle Appelhans, president and chief executive officer of COUR. “Notably, in addition to demonstrating favorable T cell responses among treated participants, CNP-104 slowed disease progression, as evidenced by a statistically significant reduction in liver stiffness measured by FibroScan by day 120 of the study period.”

Brelovitug Receives FDA Breakthrough Therapy Designation for Chronic Hepatitis Delta

Later in January, the FDA granted Breakthrough Therapy designation to Bluejay Therapeutics’ brelovitug (BJT-778) for the treatment of chronic hepatitis delta. The designation came 2 months after phase 2 data demonstrating 100% virologic response and up to 78% combined virologic response and alanine aminotransferase normalization with brelovitug monotherapy were presented at The Liver Meeting 2024 of the American Association for the Study of Liver Diseases.

According to a press release from Bluejay at the time of the phase 2 data, the company expected longer-term, 48-week data across all dose arms to be shared in the second half of 2025.

Nebokitug (CM-101) Gets FDA Runway for PSC Approval

On February 19, 2025, Chemomab Therapeutics announced the successful completion of an end-of-phase 2 meeting with the FDA as well as alignment with the agency on the design of a single phase 3 registration study for nebokitug (CM-101) for the treatment of PSC.

“Until now, the pathway to drug approval in PSC has been problematic due to the lack of validated surrogate endpoints and clarity around primary efficacy endpoints for PSC registration trials. This has been a major hindrance to the development of effective therapies for PSC,” Christopher Bowlus, MD, the Lena Valente Professor and Chief of the Division of Gastroenterology and Hepatology at the University of California Davis School of Medicine, commented. “The agreed composite endpoint approach for the nebokitug trial enhances our chances of efficiently and accurately identifying the potential clinical benefits of this promising new drug.”

Hepatic Clinical Trial Updates

Efruxifermin Reverses MASH Compensated Cirrhosis in Phase 2b SYMMETRY Study

Preliminary topline week 96 results from the phase 2b SYMMETRY study of efruxifermin in patients with biopsy-confirmed compensated cirrhosis (F4), Child-Pugh Class A, due to MASH highlight the Fc-FGF21 fusion protein’s ability to reverse cirrhosis without worsening of MASH.

In the trial, 39% of patients with baseline and week 96 biopsies who were treated with efruxifermin 50 mg experienced reversal of cirrhosis with no worsening of MASH, compared to 15% for placebo (P = .009). In the intent-to-treat population with all missing week 96 biopsies treated as failures, 29% of patients in the 50 mg efruxifermin group experienced reversal of cirrhosis with no worsening of MASH, compared to approximately 12% in the placebo group (P = .031).

Zetomipzomib Shows Promise for Autoimmune Hepatitis in Phase 2a PORTOLA Trial 

Q1 also saw the announcement of positive topline results from the PORTOLA phase 2a clinical trial of zetomipzomib in patients with autoimmune hepatitis, which showed treatment with the first-in-class selective immunoproteasome inhibitor resulted in steroid-sparing biochemical remissions in accordance with AASLD treatment guidelines in a difficult-to-treat, refractory autoimmune hepatitis patient population.

Q1 Sees New Guidance in Hepatology

AGA Releases Clinical Practice Update on HBV Reactivation Prevention, Treatment

On January 29, 2025, the American Gastroenterological Association released a clinical practice guideline update on the prevention and treatment of hepatitis B virus (HBV) reactivation in at-risk individuals, addressing research published since the first iteration was released in 2014. Specifically, it provides 4 key clinical recommendations regarding the role of antiviral prophylaxis and monitoring without antiviral prophylaxis for management of HBV reactivation based on the balance between desirable and undesirable effects, patient values, costs, and health equity considerations.

New Biliary Atresia Guidance Released by American Academy of Pediatrics

Later in Q1, the American Academy of Pediatrics released guidance providing pediatric primary care providers with a novel strategy to facilitate the early identification of biliary atresia in infants. Intended to be used between 2 and 4 weeks of life at the “By 1 month” well-child visit in the Bright Futures/AAP “Recommendations for Preventive Pediatric Health Care,” the strategy involves examining infants’ eye color, stool color, and prior laboratory results to determine whether measurement of a direct or conjugated bilirubin level is warranted.

Related: Simplifying, Expediting Biliary Atresia Diagnosis, with Ahmad Anouti, MD

Recognizing the Anniversary of Resmetirom’s FDA Approval

Celebrating 1 Year of Resmetirom, Progress in MASH/MASLD

March 14, 2025, marked the 1-year anniversary of the FDA’s accelerated approval of Madrigal Pharmaceuticals’ resmetirom (Rezdiffra) as the first and only treatment for noncirrhotic nonalcoholic steatohepatitis (NASH), now known as MASH.

In recognition of the anniversary of the landmark decision and resmetirom’s evolving impact on clinical practice and patient care, this 6-part HCPLive RX Review features insight from a trio of subject matter experts.