Hepatology Review: FDA Updates, Viral Hepatitis Research, and MASH Advancements in December 2024
Key Insights
The FDA updated safety information for obeticholic acid (Ocaliva) regarding liver injury (search) risk in primary biliary cholangitis (search) (PBC) patients without cirrhosis.
Breakthrough Therapy designation was granted to tobevibart and elebsiran by the FDA and EMA for chronic hepatitis delta (search) (CHD) treatment, based on Phase 2 SOLSTICE trial data.
Atea Pharmaceuticals reported positive Phase 2 results for bemnifosbuvir and ruzasvir in hepatitis C virus (search) (HCV) treatment, achieving a 98% SVR12 rate.
The close of 2024 saw significant developments in hepatology, marked by FDA updates, advancements in viral hepatitis research, and progress in understanding metabolic dysfunction-associated steatohepatitis (search) (MASH). Key highlights include new safety information for obeticholic acid, breakthrough therapy designations for chronic hepatitis delta (search) treatments, promising results in hepatitis C therapies, and insights into MASH progression and treatment strategies.
FDA Updates on Liver Injury Risks
The FDA announced on December 12, 2024, that postmarket clinical trial data for obeticholic acid (Ocaliva) indicated an increased risk of liver injury (search) in primary biliary cholangitis (search) (PBC) patients without cirrhosis. This update expands upon a previous Drug Safety Communication from 2021, which restricted obeticholic acid use in PBC patients with advanced cirrhosis. The agency's review revealed that even patients without cirrhosis may be vulnerable to serious liver complications, necessitating careful monitoring and risk assessment.
On December 16, 2024, the FDA added a Boxed Warning to fezolinetant (Veozah) to highlight the known risk of rare but serious liver injury (search) associated with use of the medication. The updated warning was based on the FDA’s review of a postmarketing case of serious liver injury reported to the FDA Adverse Event Reporting System (FAERS) database in a patient who experienced symptoms of fatigue; nausea; itching; yellow eyes and skin; light-colored stools; and dark urine within 40 days of starting fezolinetant.
Breakthrough Therapy Designations for Chronic Hepatitis Delta
Vir Biotechnology announced that tobevibart and elebsiran received Breakthrough Therapy designation from the FDA and Priority Medicines (PRIME) designation from the European Medicines Agency (EMA) for the treatment of chronic hepatitis delta (search) (CHD). These designations were supported by positive safety and efficacy data from the phase 2 SOLSTICE trial, building upon earlier FDA Fast Track designation and EMA Committee for Orphan Medicinal Products (COMP) positive opinion on orphan drug designation. The combination therapy represents a significant step forward in addressing this challenging viral infection.
Advancements in Viral Hepatitis Research
Atea Pharmaceuticals announced positive results from its phase 2 study of an 8-week bemnifosbuvir and ruzasvir regimen for the treatment of HCV. The trial met its primary endpoints, demonstrating a 98% sustained virologic response at 12 weeks post-treatment (SVR12) in the per-protocol treatment adherent patient population. The regimen was generally safe and well-tolerated, with no drug-related serious adverse events or treatment discontinuations. These findings suggest a potential new option for shorter-duration HCV therapy.
Insights into MASH and Novel Screening Methods
The phase 2b/3 NAVIGATE trial of Galectin Therapeutics’ belapectin in patients with MASH cirrhosis and portal hypertension did not meet its composite primary endpoint for the prevention of varices. While belapectin at both 2 mg/kg and 4 mg/kg doses reduced the incidence of varices in the intent-to-treat population, the difference over placebo was not statistically significant. This outcome underscores the challenges in developing effective therapies for advanced MASH.
Recent data suggest that artificial intelligence, specifically metabolomics-based machine learning models, could revolutionize screening for MASH patients who would benefit from resmetirom (Rezdiffra) treatment. These models have the potential to improve the accuracy, sensitivity, and predictive ability of current noninvasive testing methods, which have limitations in detecting noncirrhotic MASH with moderate-to-severe fibrosis.
An analysis of real-world data for over 18,000 US patients with MASH revealed that an eGFR of less than 60mL/min/1.73m2 (Hazard ratio [HR], 3.01) and having three or more metabolic comorbidities (HR, 1.93) were associated with increased mortality. The study also indicated a higher all-cause mortality rate among those living in the Southern United States compared to the Northeast (HR, 1.56). These findings highlight the importance of addressing renal function, metabolic comorbidities, and socioeconomic factors in managing MASH patients.