VIDEO: Larsucosterol reduces mortality by more than 50% in alcohol-associated hepatitis
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Key takeaways:
- Larsucosterol 30 mg and 90 mg reduced 90-day mortality by 41% and 35%, respectively, vs. placebo in the global population.
- In the U.S. population, larsucosterol reduced 90-day mortality by 57% and 58%.
In a Healio video exclusive, Mitchell L. Shiffman, MD, reports that U.S. patients with severe alcohol-associated hepatitis treated with larsucosterol experienced a “statistically significant” reduction in 90-day mortality — more than 50%.
“Severe alcohol use and alcoholic hepatitis significantly increased several years ago during the COVID epidemic,” Shiffman, director of the Liver Institute of Virginia at Bon Secours Mercy Health, said. “Now that COVID is behind us, alcohol use and alcoholic hepatitis continue to remain at very high levels both in the U.S. and many other countries throughout the world. There is no effective treatment for severe alcohol-associated hepatitis.”
In the randomized, placebo-controlled, phase 2b AHFIRM trial, Shiffman and colleagues enrolled 307 patients hospitalized with severe alcohol-associated hepatitis at 62 sites, 46 of which were in the U.S., to evaluate the safety and efficacy of larsucosterol.
Following a screening period, patients were randomly assigned to a single dose of larsucosterol 30 mg (n = 102) or 90 mg (n = 102) or placebo (n = 103), with administration of a second dose for patients still hospitalized 4 days later. All participants were followed for 90 days and treated according to local standard of care, with steroids given at the discretion of the primary investigator.
The primary endpoint was 90-day mortality or liver transplantation. Shiffman noted that a statistical analysis plan prespecified that data from the U.S. study arm would be reported and analyzed separately.
According to results presented at EASL Congress, death and LT in the global population was reported among 15.2% and 6.1% in the 30 mg group, respectively, 16.8% and 8.9% in the 90 mg group and 24.5% and 3.9% in the placebo group. Most of the population (78.8%, 74.3% and 71.6%) was alive and transplant-free after 90 days.
Overall, larsucosterol 30 mg and 90 mg reduced 90-day mortality by 41% and 35%, respectively, in the global population, although neither were statistically significant. However, in the U.S. population, mortality dropped by 57% and 58% compared with placebo, which did reach significance.
Further, patients in the 30 mg and 90 mg arms experienced 24% and 21% fewer treatment-emergent adverse events, which suggests larsucosterol “stabilized and improved liver function, thereby reducing the rate of complications,” Shiffman noted.
“In the United States, both larsucosterol groups exhibited statistically significant, more than a 50% reduction, in 90-day mortality,” he said. “The primary endpoint of 90-day mortality or liver transplant did not reach statistical significance in the global study, but it did reach statistical significance in the 30 mg larsucosterol group enrolled in the United States.”
Shiffman continued: “Based upon this very exciting data, the U.S. FDA has granted breakthrough therapy designation to larsucosterol for the treatment of alcohol-associated hepatitis.”
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Shiffman M, et al. Results of a phase 2b multicenter randomized trial of larsucosterol for the treatment of severe alcohol-associated hepatitis (AHFIRM trial). Presented at: EASL Congress; June 5-8, 2024; Milan (hybrid).
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