Topline data anticipated in Q4
2023
CUPERTINO, Calif., June 7, 2023
/PRNewswire/ -- DURECT Corporation (Nasdaq: DRRX), a
biopharmaceutical company developing epigenetic therapies for the
treatment of acute organ injuries and chronic liver diseases, today
announced that it has completed enrollment in its Phase
2b AHFIRM clinical trial
(NCT04563026) investigating larsucosterol for the treatment of
patients with severe alcohol-associated hepatitis (AH), achieving
its enrollment target of 300 patients.
"We are excited to have reached this critical milestone and look
forward to reporting topline data, anticipated in the fourth
quarter of 2023," said James E.
Brown, D.V.M., President and Chief Executive Officer of
DURECT. "We are preparing to file a New Drug Application (NDA) for
larsucosterol in AH pending a positive AHFIRM trial outcome and
Food and Drug Administration (FDA) guidance, and hope to expedite
regulatory discussions through the Fast Track Designation that
DURECT was previously granted by the FDA. In parallel, we are
working on the early stages of commercial launch planning in the
U.S."
Norman Sussman, M.D., FAASLD,
Chief Medical Officer at DURECT, added, "If successful, we believe
that larsucosterol will represent a treatment paradigm shift as the
first FDA-approved therapy for patients with this lethal disease.
About one-third of severe AH patients die within 90 days of
hospitalization. We look forward to building on our positive Phase
2a trial in AH and working to potentially bring a long-awaited
therapy to patients and the medical community."
About the AHFIRM Trial
AHFIRM is a Phase 2b randomized, double-blind,
placebo-controlled, international, multi-center study in subjects
with severe acute alcohol-associated hepatitis (AH) to
evaluate saFety and effIcacy of laRsucosterol
treatMent (AHFIRM). The study is comprised of three arms
evaluating a total of approximately 300 subjects, with
approximately 100 patients in each arm: (1) Placebo plus supportive
care, with or without methylprednisolone capsules at the
investigators' discretion; (2) larsucosterol (30 mg); and (3)
larsucosterol (90 mg). Patients in the larsucosterol arms received
the same supportive care without steroids. In order to
maintain blinding, patients in the two active arms received
matching placebo capsules if the investigator prescribed steroids.
The primary outcome measure will be the 90-Day incidence of death
or liver transplantation for patients treated with larsucosterol
compared to those treated with placebo. The Company has enrolled
patients at more than 60 clinical trial sites across the U.S., EU,
U.K. and Australia. Reflecting the life-threatening nature of
AH and the lack of therapeutic options, the U.S. Food and Drug
Administration (FDA) has granted larsucosterol Fast Track
Designation for the treatment of AH. We believe a positive outcome
in the AHFIRM trial could support a New Drug Application filing.
For more information, refer to ClinicalTrials.gov Identifier:
NCT04563026.
About Alcohol-Associated Hepatitis (AH)
AH is an acute
life-threatening form of alcoholic liver disease (ALD), which can
occur in individuals who chronically misuse alcohol—frequently
after increased consumption—regardless of age, gender, education or
income status. AH is typically characterized by severe inflammation
and destruction of liver tissue (i.e., necrosis), that can lead to
life-threatening complications including liver failure, acute
kidney injury and multi-organ failure. There is currently no FDA or
European Medicine Agency (EMA) approved treatment for AH, and novel
therapeutic strategies are needed to improve survival. A
retrospective analysis of 77 studies published between 1971 and
2016, which included data from a total of 8,184 patients, showed
that the overall mortality from AH was 26% at 28 days and 29% at 90
days. Stopping alcohol consumption is frequently not sufficient for
recovery in many AH patients. Treatments that reduce liver
inflammation, such as corticosteroids, have not been shown to
improve survival at 90 days or one year and have widely
acknowledged contraindications. While early liver transplantation
can improve survival in carefully selected patients with severe AH
who do not respond to medical therapy, the procedure is costly,
exceeding $875,000 in the United States on average and may be
limited by the availability of donated organs. In addition,
patients require lifelong immunosuppressive therapy to prevent
organ rejection.
About Larsucosterol
Larsucosterol is a synthetic form
of an endogenous sulfated oxysterol and an epigenetic modulator
that changes patterns of gene expression without modifying the DNA
sequence. DNA hypermethylation, an example of epigenetic
dysregulation, results in transcriptomic reprogramming and cellular
dysfunction, and has been found to be associated with many acute
(e.g., AH) or chronic diseases (e.g., NASH). Larsucosterol
binds to and inhibits the activity of DNA methyltransferases
(DNMT1, DNMT3a and 3b), epigenetic enzymes associated with DNA
methylation. By inhibiting DNMTs, larsucosterol decreases DNA
hypermethylation, thereby modulating gene expression to potentially
reduce cell death, lipotoxicity and inflammation in AH. Given its
proposed mechanism of action as an epigenetic modulator, there is
strong scientific rationale for investigating the therapeutic
potential of larsucosterol in the treatment of multiple acute organ
injuries and chronic liver diseases.
About DURECT Corporation
DURECT is a biopharmaceutical
company committed to transforming the treatment of acute organ
injuries and chronic liver diseases by advancing novel and
potentially lifesaving epigenetic therapies. Larsucosterol,
DURECT's lead drug candidate, binds to and inhibits the activity of
DNA methyltransferases (DNMTs), epigenetic enzymes associated with
hypermethylation, found to be elevated in the livers of
alcohol-associated hepatitis (AH) patients. By decreasing DNA
hypermethylation, larsucosterol modulates expression of genes
important in maintaining cellular functions, reducing cell death,
lipotoxicity and inflammation in AH. Larsucosterol is currently
being evaluated in an ongoing Phase 2b study, called AHFIRM, for the potential
treatment of AH, for which FDA has granted a Fast Track
Designation.
DURECT Forward-Looking Statements
This press release contains forward-looking statements, including
statements made pursuant to the safe harbor provisions of the
Private Securities Litigation Reform Act of 1995, relating to: our
plan to report topline data in the fourth quarter of 2023, the
potential FDA approval of larsucosterol for the treatment of AH,
the ability of a positive outcome in the AHFIRM trial to support a
New Drug Application (NDA) filing and our ability to expedite the
NDA process using the Fast Track Designation granted by the FDA,
larsucosterol's potential to be the first FDA-approved therapy for
AH, our plans to commercialize larsucosterol if approved, the
potential to develop larsucosterol for AH or other indications, and
the potential benefits, if any, of our product candidates. Actual
results may differ materially from those contained in the
forward-looking statements contained in this press release, and
reported results should not be considered as an indication of
future performance. The potential risks and uncertainties that
could cause actual results to differ from those projected include,
among other things, the risk that ongoing and future clinical
trials of larsucosterol do not confirm the results from earlier
clinical or pre-clinical trials, or do not demonstrate the safety
or efficacy of larsucosterol in a statistically significant manner,
the risk that the FDA or other government agencies may require
additional clinical trials for larsucosterol before approving it
for the treatment of AH even if the results of the AHFIRM trial are
successful, and risks related to the sufficiency of our cash
resources, our anticipated capital requirements, our need or desire
for additional financing, our ability to obtain capital to fund our
operations and expenses and our ability to continue to operate as a
going concern. Further information regarding these and other risks
is included in DURECT's most recent Securities and Exchange
Commission (SEC) filings, including its annual report on Form 10-K
for the year ended December 31, 2022
and quarterly report on Form 10-Q for the quarter ended
March 31, 2023 under the heading
"Risk Factors." These reports are available on our website
www.durect.com under the "Investors" tab and on the SEC's website
at www.sec.gov. All information provided in this press release and
in the attachments is based on information available to DURECT as
of the date hereof, and DURECT assumes no obligation to update this
information as a result of future events or developments, except as
required by law.
NOTE: Larsucosterol is an investigational drug candidate under
development and has not been approved for commercialization by the
U.S. Food and Drug Administration or other health authorities for
any indication.
View original content to download
multimedia:https://www.prnewswire.com/news-releases/durect-completes-enrollment-in-phase-2b-ahfirm-trial-of-larsucosterol-in-alcohol-associated-hepatitis-301844490.html
SOURCE DURECT Corporation