DURECT Corporation Receives FDA Breakthrough Therapy Designation for Larsucosterol in Alcohol-Associated Hepatitis
DURECT (Nasdaq: DRRX) has received Breakthrough Therapy designation (BTD) from the FDA for larsucosterol, aimed at treating severe alcohol-associated hepatitis (AH). AH has no approved treatments and high mortality rates, making the designation crucial. The decision is backed by positive results from the Phase 2b AHFIRM trial. DURECT plans to initiate a Phase 3 clinical trial to confirm the efficacy and safety of larsucosterol. Detailed results will be presented at the EASL Congress 2024 in Milan on June 8, 2024.
- Breakthrough Therapy designation by FDA for larsucosterol.
- Larsucosterol shows potential in treating severe alcohol-associated hepatitis, which has no current treatments.
- Backed by positive Phase 2b AHFIRM trial results.
- Plans for a registrational Phase 3 trial to confirm efficacy and safety.
- Presentation of detailed Phase 2b results at EASL Congress.
- No current approved treatments for AH, indicating a high-risk area.
- Pending Phase 3 trial outcomes could delay market entry.
- Dependence on FDA guidance and approval processes.
Insights
The recent FDA Breakthrough Therapy designation for larsucosterol is a significant milestone for DURECT Corporation. This designation is awarded to therapies that demonstrate substantial improvement over existing treatments for serious conditions. Given the absence of approved treatments for severe alcohol-associated hepatitis (AH), this development is monumental.
From a clinical perspective, larsucosterol's progression from Phase 2b to a planned Phase 3 trial highlights its potential effectiveness. The Phase 2b trial's double-blind, placebo-controlled structure ensures robust and reliable data. The promising results, coupled with the FDA's feedback, pave the way for a potentially expedited approval process, pending successful outcomes in the Phase 3 trial.
For investors, this designation can significantly reduce the timeframe for larsucosterol’s market entry, assuming successful trial results. The potential for expedited communication and review from the FDA can be a catalyst for both short-term market gains and long-term growth, provided that future data continues to support its efficacy and safety.
From a financial perspective, the FDA's Breakthrough Therapy designation for larsucosterol could have a substantial impact on DURECT Corporation's valuation. This designation not only underscores the drug’s potential but also can accelerate its path to market, which is often viewed positively by the market.
Investors should consider the potential market size for a treatment in severe alcohol-associated hepatitis, a condition with high mortality and no current approved therapies. This could represent a multi-billion dollar market opportunity. Additionally, the expedited review process can lead to earlier revenue generation, which is important for a biopharmaceutical company at this stage.
Moreover, this designation can enhance DURECT's attractiveness as an acquisition target, given the significant unmet medical need and the strong clinical data supporting larsucosterol’s efficacy. However, investors should remain mindful of the inherent risks associated with clinical trials and regulatory approvals.
The market implications of DURECT receiving Breakthrough Therapy designation for larsucosterol are noteworthy. This designation typically stimulates positive market sentiment due to the potential for expedited development and review processes. Given the high unmet need in treating severe alcohol-associated hepatitis, the market's response is likely to be favorable.
In the short term, this news can elevate DURECT's stock price as investors react to the potential for rapid progress. In the long term, the successful commercialization of larsucosterol could substantially enhance DURECT's market position, especially if they secure a significant market share in the AH treatment space.
Investors should also consider the competitive landscape. While larsucosterol holds promise, monitoring other ongoing research and potential competitors is crucial. The designation itself does not guarantee approval, so market dynamics will continue to evolve based on emerging data and regulatory milestones.
DURECT plans to confirm the efficacy and safety of larsucosterol in a registrational Phase 3 clinical trial
"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, D.V.M., President and CEO of DURECT. "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 were 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, 2024 in
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.
About the AHFIRM Trial
AHFIRM was a Phase 2b randomized, double-blind, placebo-controlled, international, multi-center study conducted in subjects with severe alcohol-associated hepatitis (AH) to evaluate the saFety and effIcacy of laRsucosterol treatMent (AHFIRM). The study was comprised of three arms and enrolled 307 patients, with approximately 100 patients in each arm: (1) placebo, which consisted of standard of 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. The primary outcome measure was the 90-Day incidence of mortality or liver transplantation for patients treated with larsucosterol compared to those treated with placebo, and the key secondary endpoint was 90-Day survival. The Company enrolled patients at clinical trial sites across the
About Alcohol-associated Hepatitis (AH)
AH is an acute form of alcohol-associated liver disease (ALD) associated with long-term heavy alcohol intake, often following a recent period of increased consumption (i.e., a binge). AH 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 AH, and a retrospective analysis of 77 studies published between 1971 and 2016, which included data from 8,184 patients, showed the overall mortality from AH was
About Larsucosterol
Larsucosterol is an endogenous sulfated oxysterol and an epigenetic modulator. Epigenetic regulators are compounds that regulate 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 reported in many acute (e.g., AH) and chronic diseases (e.g., MASH). As an inhibitor of DNA methyltransferases (DNMT1, DNMT3a and 3b), larsucosterol inhibits DNA methylation, which subsequently modulates the expression of genes that are involved in cell signaling pathways associated with stress responses, cell death and survival, and lipid biosynthesis. This may ultimately lead to improved cell survival, reduced inflammation, and decreased lipotoxicity. As an epigenetic modulator, the proposed mechanism of action provides further scientific rationale for developing larsucosterol for the treatment of acute organ injury and certain chronic diseases.
About DURECT Corporation
DURECT is a late-stage biopharmaceutical company pioneering the development of epigenetic therapies that target dysregulated DNA methylation to transform the treatment of serious and life-threatening conditions, including acute organ injury and cancer. Larsucosterol, DURECT's lead drug candidate, binds to and inhibits the activity of DNA methyltransferases (DNMTs), epigenetic enzymes that are elevated and associated with hypermethylation found in alcohol-associated hepatitis (AH) patients. Larsucosterol is in clinical development for the potential treatment of AH, for which the FDA has granted a Fast Track and a Breakthrough Therapy designation; metabolic dysfunction-associated steatohepatitis (MASH) is also being explored. In addition, POSIMIR® (bupivacaine solution) for infiltration use, a non-opioid analgesic utilizing the innovative SABER® platform technology, is FDA-approved and is exclusively licensed to Innocoll Pharmaceuticals for sale and distribution in
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: the potential benefits of Breakthrough Therapy designation, and the potential uses and benefits of laruscosterol in patients with AH and potentially other indications. 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 future clinical trials of larsucosterol are delayed or do not confirm the results from subset analyses of the AHFIRM trial, including geographic or other segmentation, or of 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 larsucosterol for the treatment of AH, the risk that Breakthrough Therapy designation does not expedite the process for FDA approval and that larsucosterol may never be approved; risks that Innocoll may not commercialize POSIMIR successfully; and risks related to the sufficiency of our cash resources, our anticipated capital requirements, our need or desire for additional financing, our ability to continue to meet the minimum bid price for continued listing on Nasdaq, 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, 2023 and quarterly report on Form 10-Q for the quarter ended March 31, 2024, 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: POSIMIR® is a trademark of Innocoll Pharmaceuticals, Ltd. in the
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FAQ
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