New Treatment for AA Hepatitis: Larsucosterol Earns FDA Breakthrough Designation

Larsucosterol, a new treatment option for severe alcohol-associated hepatitis, earns FDA Breakthrough Designation. Supported by promising results from the Phase 2b trial, larsucosterol, the first-of-its-kind treatment for alcohol-associated hepatitis, shows potential to improve survival and reduce liver inflammation.

DURECT Corporation has announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to its novel drug, larsucosterol, for the treatment of severe alcohol-associated hepatitis (AH)—a condition with no currently approved treatments and high mortality rates. This designation is a significant milestone and underscores the potential of larsucosterol to transform the treatment landscape for this life-threatening condition.

The company is preparing to launch a registrational Phase 3 clinical trial to confirm the efficacy and safety of larsucosterol, with further details to be presented at the upcoming European Association for the Study of the Liver (EASL) Congress.

James E. Brown, D.V.M., President and CEO of DURECT, expressed his satisfaction with the FDA’s decision, “AH has a high mortality rate and no currently approved treatments, so there is a great need for a safe and effective therapy. We continue to finalize the design of our planned registrational Phase 3 trial for larsucosterol, incorporating the recent FDA feedback and promising data from our completed Phase 2b AHFIRM trial.”

The Promise of Larsucosterol

Larsucosterol is a novel epigenetic modulator designed to inhibit DNA methylation, a process that can lead to cellular dysfunction and disease. By targeting the DNA methyltransferases DNMT1, DNMT3a, and 3b, larsucosterol potentially modulates gene expression to reduce inflammation, enhance cell survival, and decrease harmful lipid accumulation in the liver.

Larsucosterol's designation was supported by promising data from the Phase 2b AHFIRM trial—a rigorous, double-blind, placebo-controlled study that enrolled 307 patients across multiple international sites. Preliminary results suggest that larsucosterol could significantly improve survival outcomes without the side effects associated with current treatments.

Next Steps for Larsucosterol

With the Breakthrough designation, DURECT Corporation will benefit from enhanced FDA guidance, a streamlined review process, and the possibility of accelerated approval. The company is finalizing plans for a pivotal Phase 3 trial, taking into account feedback from the FDA and data from earlier studies.

What is Alcohol-Associated Hepatitis?

Alcohol-associated hepatitis is an acute and severe form of liver disease that results from long-term heavy drinking, often exacerbated by recent binge episodes. Characterized by intense liver inflammation and cell damage, AH can lead to dire complications such as liver failure and multi-organ dysfunction. Current treatments, including corticosteroids, are limited and have not been shown to significantly improve survival rates beyond 90 days or reduce the risk of infection. With no FDA-approved treatments available and a high mortality rate—26% at 28 days, rising to 44% at 180 days—AH is a condition in desperate need of effective therapies.

About Author: Tracy Mokwe

With over 3 years of experience as a medical laboratory scientist and writer, I am passionate about translating complex scientific information into clear and accessible content. My expertise lies in medical sciences, laboratory science and research, digital health, AI, and cybersecurity in healthcare.