Hepatology Month in Review: May 2024

Coming off of a historic first quarter of 2024, May was a fitting continuation to what has thus far been a groundbreaking year in hepatology. Although pipeline news was largely negative with Dynavax’s receipt of a Complete Response Letter (CRL) for their HEPLISAV-B supplemental Biologic License Application (sBLA), Digestive Disease Week (DDW) 2024 was full of promising hepatic pipeline movement and other important liver disease research. Beyond HCPLive’s coverage of the conference, the 2024 hepatology month in review also spotlights top hepatitis C virus (HCV) and alpha-1 antitrypsin deficiency (AATD) content from the past few weeks.

Pipeline Updates

FDA Issues CRL for HEPLISAV-B in Adults on Hemodialysis

In hepatic pipeline news, the FDA issued a CRL to Dynavax’s sBLA to include a 4-dose HEPLISAV-B vaccination [Hepatitis B Vaccine (Recombinant), Adjuvanted] regimen for adults on hemodialysis, citing insufficient data to support the full evaluation of effectiveness or safety of this regimen.

"We remain confident in the data generated to support HEPLISAV-B vaccination for adult hemodialysis patients. All key data collected in HBV-24 were verified against original source documents during the conduct of the trial," Rob Janssen, MD, Chief Medical Officer of Dynavax, said in a press release. "We are reviewing the agency's feedback and intend to request a meeting with the FDA to evaluate options for providing additional data to support the four-dose regimen for this vulnerable patient population in the U.S."

HCPLive at DDW

Naim Alkhouri, MD: Interim Analysis of Phase 2 Survodutide Data Show Promise for MASH, Fibrosis

Coming on the heels of resmetirom (Rezdiffra)’s historic FDA approval in March, new phase 2 data for survodutide were presented during a late-breaking session at DDW and highlighted the novel glucagon receptor/glucagon-like peptide (GLP)-1 receptor dual agonist’s impact on liver fat content, transaminases, and markers of fibrosis. The pre-planned interim analysis detailed efficacy and safety results at week 28 among 138 participants who were randomly assigned to receive once-weekly subcutaneous injections of placebo or survodutide 2.4, 4.8, or 6.0 mg escalated over up to 24 weeks from a starting dose of 0.3 mg for 48 weeks.

ASSURE: Seladelpar Achieves Clinical Improvement in Primary Biliary Cholangitis

Another interim analysis presented at DDW showed seladelpar, a selective PPAR-delta agonist, was associated with clinically meaningful improvements in markers of cholestasis and liver injury, also demonstrating an overall strong signal of safety and tolerability through month 12 of the phase 3 ASSURE trial for the treatment of primary biliary cholangitis (PBC).

Related: Cynthia Levy, MD: Interim ASSURE Data Suggest Seladelpar Could Be “Transformative” in PBC

Elizabeth Aby, MD: Financial Burden in Adults Undergoing Liver Transplant Evaluation

A pair of studies presented at DDW highlighted multiple facets of the financial impact of chronic liver disease by looking at health-related quality of life and social risk factors in adults undergoing liver transplant evaluation. Results from both studies showed high financial burden was linked to greater symptom burden; shortness of breath; anxiety; lower health-related quality of life; healthcare-related financial insecurity; housing insecurity; and transportation insecurity.

Barriers to Hepatitis Treatment

Social Determinants of Health May Limit Linkage to Outpatient HCV Care

A recent case-control retrospective chart review found patients who missed their initial scheduled infectious disease clinic appointment for HCV treatment had greater rates of housing instability, transportation difficulties, and medication non-adherence compared to patients who attended their first treatment appointment.

“Our study highlights the role of social determinants of health in care transitions, particularly within the transition to outpatient HCV care,” Carlo Foppiano Palacios, MD, assistant professor of medicine and infectious diseases specialist at Cooper Medical School of Rowan University, and colleagues wrote.

Unstable Housing May Be a Barrier to HCV Treatment Among People Who Inject Drugs

Compared to stable housing, a recent study suggests unstable housing may lead to poorer treatment outcomes among people who inject drugs (PWID) with HCV. Specifically, results point to the negative impact on direct-acting antiviral (DAA) initiation in this patient population.

“In order to reach HCV elimination targets, we must reach highly burdened populations such as PWID experiencing unstable housing,” Sarah Kimball, MPH, doctoral student concentrating in epidemiology at New York University School of Global Public Health, and colleagues wrote.

Improving AATD Care

A1AT Phenotyping Lags Behind, Contributes to Underrecognition of AATD

Findings from a recent analysis suggest education on alpha-1 antitrypsin (A1AT) phenotyping for healthcare providers in the US may be lacking, supported by data showing phenotyping was performed in less than 50% of patients in the single-center study.

We propose that regular continuous medical educational programs about A1AT phenotyping targeting healthcare providers are warranted,” Zane Elfessi, PharmD, and colleagues wrote.

Biomarker, Treatment Development Could Help Address Unmet Need in AATD-Related Liver Disease

A recent review article is shining light on the latest advancements in biomarkers and clinical drug development in the context of AATD-related liver disease. Using available literature, a multi-stakeholder forum organized by the Alpha-1 Antitrypsin Deficiency Related Liver Disease Expert Panel examined the current understanding of the disease, highlighted emerging biomarkers, and explored strategies for clinical drug development.

“As the field gathers momentum, forums such as this will galvanise the community in its drive to improving the lives of people with AATLD around the world,” Rohit Loomba, MD, MHSc, chief of the division of gastroenterology and hepatology at the University of California at San Diego, and colleagues wrote.