Durect Corporation is a late-stage biopharma company championing the development of epigenetic therapies to transform the treatment of serious and life-threatening conditions such as acute organ injury and cancer through the use of larsucosterol.
James E. Brown, president and CEO of Durect, said: “We’re pleased with the FDA’s decision to grant Breakthrough Therapy designation to larsucosterol, as it further recognizes its potential to save the lives of AH patients.”
“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. We look forward to releasing additional clinical data on larsucosterol and potentially bringing this therapy to patients as soon as possible.”
The BTD is supported by clinical evidence from the phase 2b AHFIRM trial, a double-blind, placebo-controlled, international, multi-center study, which evaluated the safety and efficacy of larsucosterol as a treatment for patients with severe AH.
Topline data from the study was announced in 2023, and further details will be shared in a late-breaking oral presentation at the European Association for the Study of the Liver (EASL) Congress 2024 on June 8, in Milan, Italy.
BTD is designed to expedite the development and review of therapies intended to treat a serious or life-threatening condition and whose preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on one or more clinically significant endpoints over existing available therapies. BTD provides therapeutics with all the benefits from a Fast Track designation, such as early and frequent communication with the FDA, eligibility for rolling review and other actions to expedite review, in addition to intensive guidance and organizational commitment involving senior FDA managers. BTD does not change the standards for product approval but may expedite the process.
AH is an acute form of alcohol-associated liver disease associated with long-term heavy alcohol intake, often following a recent period of increased consumption such as a binge. It is typically characterized by severe inflammation and liver cell damage, potentially leading to life-threatening complications including liver failure, acute kidney injury and multi-organ failure.
There are no FDA approved therapies for this disease, and a retrospective analysis of 77 studies published between 1971 and 2016, which included data from 8,184 patients, showed the overall mortality from alcohol-associated hepatitis was 26% at 28 days, 29% at 90 days and 44% at 180 days.
A subsequent global study published in December 2021, which included 85 tertiary centers in 11 countries across 3 continents, prospectively enrolled 2,581 AH patients with a median Model of End-Stage Liver Disease (MELD) score of 23.5, reported mortality at 28 and 90 days of approximately 20% and 31%, respectively.
It is important to stop alcohol consumption, but it is frequently not enough for many in moderate (defined as MELD scores of 11-20) and severe (defined as MELD scores >20) patients. Treatments that reduce liver inflammation including corticosteroids are limited by contraindications and have not shown to improve survival at 90 days or a year and have shown an increased risk of infection.
While liver transplantation is becoming more common for ALD patients, including AH patients, the total number of such transplants is still relatively small and limited by organ availability. Average charges for a liver transplant exceed $875,000, and patients require lifelong immunosuppressive therapy to prevent organ rejection.
