Don Tracy, Associate Editor

Moving forward, Durect plans on incorporating feedback from the FDA in the design of a Phase III trial.
DURECT Corporation announced that the FDA has granted Breakthrough Therapy Designation (BTD) to larsucosterol, a medication that aims to treat patients with severe alcohol-associated hepatitis (AH). According to the company, the designation is based on positive results from the Phase IIb AHFIRM trial, which demonstrated positive safety and efficacy outcomes, with the first portion of data being announced last year, while additional clinical data is expected to be presented at the. European Association for the Study of the Liver (EASL) Congress next month.1
“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,” said James E. Brown, DVM, President, CEO, DURECT, in a press release. “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 III trial for larsucosterol, incorporating the recent FDA feedback and promising data from our completed Phase IIb AHFIRM trial. We look forward to releasing additional clinical data on larsucosterol and potentially bringing this therapy to patients as soon as possible.”
The AHFIRM Phase IIb trial, which was a randomized, double-blind, placebo-controlled, international, multi-center study conducted in subjects with AH, aimed to evaluate the safety and efficacy of larsucosterol. Enrolling a total of 307 patients through three arms of the trial, the primary outcome measure focused on the 90-Day incidence of mortality or liver transplantation for patients treated with larsucosterol compared to those treated with placebo, with 90-day survival being the secondary endpoint.1
As allude to above, data released to the public in November indicated that larsucosterol doses of both 30 mg and 90 mg demonstrated a noteworthy trend in reduction of mortality at 90 days. However, numerical improvement of mortality or transplant at 90 days didn’t achieve statistical significance. Approximately 76% of patients enrolled in the trial displayed a more distinct reduction in mortality compared to placebo.2
"The topline results from AHFIRM provide compelling evidence that administration of larsucosterol can reduce mortality at 90 days in this devastating disease," said Brown, D.V.M., in a press release."We have strong rationale to advance larsucosterol into a Phase III registration trial designed with adequate power to detect a statistically significant result using 90-day mortality as the primary endpoint. We look forward to meeting with the FDA to discuss next steps.Based on the strength of the clinical data generated to date, if approved, larsucosterol could save many patient lives.We extend our thanks to all the patients, families, clinical trial investigators, and staff across the multiple sites globally who have worked with the DURECT team to bring larsucosterol to this advanced stage."
According to Hopkins Medicine, common symptoms of AH include tenderness in the abdomen, nausea, weight loss, poor appetite, and vomiting blood or material that looks like coffee grounds. It can be diagnoses through blood tests, abdomen ultrasounds, CT scans, MRI, and liver biopsies.3
“Alcoholic hepatitis most often happens in people who drink heavily over many years. But the link between drinking and alcoholic hepatitis isn't simple. Not all heavy drinkers get alcoholic hepatitis. And some people who drink much less get the disease,” reports the Mayo Clinic.4