DURECT Corporation Announces Publication of Larsucosterol Phase 2b Results in NEJM Evidence
DURECT (DRRX) has published Phase 2b AHFIRM trial results for larsucosterol in NEJM Evidence. The trial evaluated the drug's safety and efficacy in treating severe alcohol-associated hepatitis (AH) across 307 patients in three arms: placebo, 30mg, and 90mg doses.
The study showed clinically meaningful trends in reducing 90-day mortality, with 41% reduction in the 30mg arm (p=0.068) and 35% in the 90mg arm (p=0.124) compared to placebo. Results were more pronounced in U.S. patients, showing mortality reductions of 57% (p=0.014) and 58% (p=0.008) for 30mg and 90mg doses respectively.
The company plans to initiate a Phase 3 trial in 2025, pending funding. The FDA has indicated that a single Phase 3 trial could support a New Drug Application (NDA). The drug appeared safe and well-tolerated, with treatment emergent adverse events similar to placebo.
DURECT (DRRX) ha pubblicato i risultati della sperimentazione clinica Phase 2b AHFIRM per il larsucosterol su NEJM Evidence. Lo studio ha valutato la sicurezza e l'efficacia del farmaco nel trattamento dell'epatite severa associata all'alcol (AH) su 307 pazienti suddivisi in tre gruppi: placebo, dosi da 30mg e 90mg.
La ricerca ha mostrato tendenze clinicamente significative nella riduzione della mortalità a 90 giorni, con una riduzione del 41% nel gruppo da 30mg (p=0.068) e del 35% nel gruppo da 90mg (p=0.124) rispetto al placebo. I risultati sono stati più evidenti nei pazienti statunitensi, che hanno mostrato riduzioni della mortalità del 57% (p=0.014) e del 58% (p=0.008) rispettivamente per le dosi da 30mg e 90mg.
L'azienda prevede di avviare una sperimentazione di fase 3 nel 2025, in attesa di finanziamenti. La FDA ha indicato che una singola sperimentazione di fase 3 potrebbe supportare una domanda di nuovo farmaco (NDA). Il farmaco è apparso sicuro e ben tollerato, con eventi avversi emergenti dal trattamento simili a quelli del placebo.
DURECT (DRRX) ha publicado los resultados del ensayo clínico de fase 2b AHFIRM para larsucosterol en NEJM Evidence. El ensayo evaluó la seguridad y eficacia del medicamento en el tratamiento de la hepatitis grave asociada al alcohol (AH) en 307 pacientes en tres grupos: placebo, dosis de 30mg y 90mg.
El estudio mostró tendencias clínicamente significativas en la reducción de la mortalidad a 90 días, con una reducción del 41% en el grupo de 30mg (p=0.068) y del 35% en el grupo de 90mg (p=0.124) en comparación con el placebo. Los resultados fueron más pronunciados en pacientes de EE. UU., mostrando reducciones de mortalidad del 57% (p=0.014) y 58% (p=0.008) para las dosis de 30mg y 90mg, respectivamente.
La empresa planea iniciar un ensayo de fase 3 en 2025, pendiente de financiamiento. La FDA ha indicado que un único ensayo de fase 3 podría respaldar una Solicitud de Nuevo Medicamento (NDA). El medicamento pareció seguro y bien tolerado, con eventos adversos emergentes del tratamiento similares al placebo.
DURECT (DRRX)는 NEJM Evidence에서 larsucosterol에 대한 2b 단계 AHFIRM 시험 결과를 발표했습니다. 이 시험은 307명의 환자를 대상으로 알코올 연관 간염(AH) 치료 시 약물의 안전성과 효능을 평가했습니다. 시험에는 위약군, 30mg, 90mg 용량의 세 그룹이 포함되었습니다.
연구 결과 90일 사망률 감소의 임상적으로 의미 있는 경향이 나타났으며, 30mg 군에서 41% 감소(p=0.068), 90mg 군에서 35% 감소(p=0.124)가 위약군에 비해 관찰되었습니다. 미국 환자에서 결과가 더 뚜렷하게 나타났으며, 30mg 및 90mg 용량에서 각각 57% (p=0.014) 및 58% (p=0.008) 의 사망률 감소가 관찰되었습니다.
회사는 2025년에 3상 시험을 시작할 계획이며, 자금이 확보되는 대로 진행할 예정입니다. FDA는 단일 3상 시험이 신규 약물 신청(NDA)을 지원할 수 있다고 밝혔습니다. 이 약물은 안전하고 잘 견뎌졌으며, 치료에서 발생한 불리한 사건도 위약과 유사한 수준으로 관찰되었습니다.
DURECT (DRRX) a publié les résultats de l'essai clinique de phase 2b AHFIRM pour le larsucosterol dans NEJM Evidence. L'essai a évalué la sécurité et l'efficacité du médicament dans le traitement de l'hépatite sévère associée à l'alcool (AH) chez 307 patients répartis en trois groupes : placebo, doses de 30mg et 90mg.
L'étude a montré des tendances cliniquement significatives dans la réduction de la mortalité à 90 jours, avec une réduction de 41 % dans le groupe de 30mg (p=0.068) et de 35 % dans le groupe de 90mg (p=0.124) par rapport au placebo. Les résultats étaient plus prononcés chez les patients américains, montrant des réductions de mortalité de 57 % (p=0.014) et 58 % (p=0.008) pour les doses de 30mg et 90mg respectivement.
L'entreprise prévoit de commencer un essai de phase 3 en 2025, en attente de financements. La FDA a indiqué qu'un essai unique de phase 3 pourrait soutenir une demande de nouveau médicament (NDA). Le médicament a semblé sûr et bien toléré, avec des événements indésirables émergents similaires à ceux du placebo.
DURECT (DRRX) hat die Ergebnisse der Phase 2b AHFIRM-Studie zu Larsucosterol in NEJM Evidence veröffentlicht. Die Studie bewertete die Sicherheit und Wirksamkeit des Medikaments zur Behandlung von schwerer alkoholbedingter Hepatitis (AH) bei 307 Patienten in drei Gruppen: Placebo, 30mg und 90mg Dosen.
Die Studie zeigte klinisch relevante Trends zur Reduzierung der 90-Tage-Sterblichkeit, mit einer 41%igen Reduzierung in der 30mg-Gruppe (p=0.068) und einer 35%igen Reduzierung in der 90mg-Gruppe (p=0.124) im Vergleich zur Placebo-Gruppe. Die Ergebnisse waren bei US-Patienten ausgeprägter und zeigten Sterblichkeitsreduktionen von 57% (p=0.014) und 58% (p=0.008) für die Dosen von 30mg und 90mg.
Das Unternehmen plant, eine Phase-3-Studie im Jahr 2025 zu beginnen, vorbehaltlich der Finanzierung. Die FDA hat angedeutet, dass eine einzelne Phase-3-Studie einen Antrag auf Zulassung eines neuen Medikaments (NDA) unterstützen könnte. Das Medikament erwies sich als sicher und gut verträglich, mit behandlungsbedingten Nebenwirkungen ähnlich wie im Placebo.
- Significant mortality reduction in U.S. patients (57-58%) with strong statistical significance (p<0.014)
- FDA agreement that single Phase 3 trial could support NDA
- Drug demonstrated good safety profile with adverse events similar to placebo
- Publication in prestigious NEJM Evidence journal adds credibility
- Primary endpoint of mortality or liver transplant at 90 days did not achieve statistical significance
- Phase 3 trial initiation dependent on securing funding
- Overall mortality reduction (35-41%) didn't reach statistical significance (p>0.05)
Insights
The publication of DURECT's Phase 2b AHFIRM trial results in NEJM Evidence marks a potentially transformative development in the treatment of alcohol-associated hepatitis (AH), a condition with a devastating 33% mortality rate within three months.
The trial data reveals several critical insights: First, the pronounced efficacy in U.S. patients, with mortality reductions of
The safety profile is particularly noteworthy, as treatment-emergent adverse events were comparable to placebo - a important advantage in a patient population with compromised liver function. This favorable safety profile, combined with the mortality benefit, positions larsucosterol as a potentially groundbreaking therapy in a field where previous treatments have consistently failed.
The FDA's willingness to consider a single Phase 3 trial for NDA submission reflects the urgent unmet need in AH treatment. However, the company's emphasis on pending funding for the Phase 3 trial introduces uncertainty about the timeline to market. The focus on 90-day mortality as the primary endpoint for Phase 3 is strategically sound, as it aligns with the strongest efficacy signals from Phase 2b and addresses a clear clinical need.
The article presents new trial data, including subgroup analyses and liver biomarkers, which have guided the design of the Company's planned Phase 3 trial
The AHFIRM trial was a Phase 2b randomized, double-blind, placebo-controlled, international, multi-center study that evaluated the safety and efficacy of the Company's epigenetic modulator, larsucosterol, for the treatment of subjects with severe alcohol-associated hepatitis (AH). It enrolled 307 patients across three arms: placebo, which consisted of standard of care, with or without methylprednisolone capsules at the investigators' discretion, larsucosterol (30 mg) and larsucosterol (90 mg). A total of 62 centers enrolled patients including 46 US sites that enrolled
"We are encouraged by the AHFIRM data and look forward to further assessing the benefits of larsucosterol in AH patients in a Phase 3 trial," said Dr. Mitchell Shiffman, Director of the Liver Institute of
Norman Sussman, MD, FAASLD, Chief Medical Officer of DURECT, commented, "The publication of the AHFIRM data in such an esteemed journal underscores the importance of the clinical findings -- we are pleased to share the detailed results with the broader scientific and medical communities. Additional analyses in this article highlight regional differences in patient populations and in AH treatment regimens including time from hospital admission to treatment and the use of liver transplantation. This comprehensive analysis has guided us in designing a robust Phase 3 trial protocol to focus on
James E. Brown, D.V.M., President and CEO of DURECT, added, "We look forward to further demonstrating larsucosterol's potential in our upcoming Phase 3 trial. If successful, the Food and Drug Administraton (FDA) has agreed that a single Phase 3 trial could be sufficient to support a New Drug Application (NDA). We plan to initiate the trial in 2025, pending funding."
Key data highlights from the AHFIRM trial, include:
- Both the 30 mg and 90 mg larsucosterol doses demonstrated clinically meaningful trends in reducing 90-day mortality with mortality reductions of
41% (p=0.068) in the 30 mg arm and35% (p=0.124) in the 90 mg arm compared with placebo. - The reductions in mortality at 90 days were more pronounced in
U.S. patients with reductions of57% (p=0.014) in the 30 mg arm and58% (p=0.008) in the 90 mg arm compared with placebo; computations for random sample analysis suggest that theU.S. results of larsucosterol treatment were unlikely to be an artifact of random chance. - The numerical improvement in the primary endpoint of mortality or liver transplant at 90 days did not achieve statistical significance for either dose of larsucosterol.
- Variations in time from hospitalization to first dose highlighted the importance of timely treatment in patients with severe AH.
- Larsucosterol appeared safe and well tolerated in the AHFIRM trial and the number of treatment emergent adverse events (TEAEs) and newly-occurring significant complications of liver disease in both larsucosterol groups were similar to those in placebo.
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 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. Larsucosterol, DURECT's lead drug candidate, binds to and inhibits the activity of DNA methyltransferases, epigenetic enzymes that are elevated and associated with hypermethylation found in 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; 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. For more information about DURECT, please visit www.durect.com and follow us on X (formerly Twitter) at https://x.com/DURECTCorp.
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 plans to conduct a Phase 3 clinical trial of larsucosterol, the ability of the Phase 3 trial, if successful, to support an NDA filing, the sufficiency of our capital requirements through the first half of 2025 and the potential uses of larsucosterol to treat 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 we do not raise sufficient capital to commence or complete the Phase 3 clinical trial of larsucosterol in patients with AH or continue to fund our operations, 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; and risks related to the sufficiency of our cash resources, our anticipated capital requirements, our ability to meet the minimum bid price for continued listing on Nasdaq, 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 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 September 30, 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 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
View original content to download multimedia:https://www.prnewswire.com/news-releases/durect-corporation-announces-publication-of-larsucosterol-phase-2b-results-in-nejm-evidence-302362158.html
SOURCE DURECT Corporation
FAQ
What were the key results of DRRX's Phase 2b AHFIRM trial for larsucosterol?
When will DRRX begin Phase 3 trials for larsucosterol?
How many patients were enrolled in DRRX's AHFIRM trial?
What is the FDA's requirement for DRRX's larsucosterol approval?
What was the safety profile of DRRX's larsucosterol in the AHFIRM trial?
