DURECT公司宣布在NEJM证据中公布Larsucosterol 2b期结果-动脉网

DURECT Corporation Announces Publication of Larsucosterol Phase 2b Results in NEJM Evidence

CISION 等信源发布 2025-01-28 23:09

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可切换为仅中文

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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

本文介绍了新的试验数据，包括亚组分析和肝脏生物标志物，这些数据指导了该公司计划的3期试验的设计

CUPERTINO, Calif.

加利福尼亚州库比蒂诺。

Jan. 28, 2025

2025年1月28日

/PRNewswire/ -- DURECT Corporation (Nasdaq:

/PRNewswire/--DURECT Corporation（纳斯达克：

DRRX

) today announced the publication of a peer-reviewed article on the AHFIRM trial data in

)今天宣布发表一篇关于AHFIRM试验数据的同行评审文章

NEJM Evidence

NEJM 证据

. The full article, entitled, 'Larsucosterol for the Treatment of Alcohol-Associated Hepatitis,' can be accessed

全文题为“用于治疗酒精相关性肝炎的拉苏固醇”，可以访问

here

在这里

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).

AHFIRM试验是一项2b期随机，双盲，安慰剂对照，国际性，多中心研究，评估了该公司表观遗传调节剂larsucosterol治疗严重酒精相关性肝炎（AH）患者的安全性和有效性。它在三组中招募了307名患者：安慰剂，由标准护理组成，由研究人员决定是否使用甲基强的松龙胶囊，larsucosterol（30 mg）和larsucosterol（90 mg）。

A total of 62 centers enrolled patients including 46 US sites that enrolled 76% of patients. Topline results from AHFIRM were previously announced by DURECT..

共有62个中心招募了患者，其中46个美国站点招募了76%的患者。DURECT之前公布了一家公司的业绩。。

'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.

“我们对AHFIRM的数据感到鼓舞，并期待在3期临床试验中进一步评估拉舒固醇对AH患者的益处，”Dr。

Mitchell Shiffman

米切尔·希夫曼

, Director of the Liver Institute of

，肝脏研究所所长

Virginia

弗吉尼亚州

and lead study author. 'Many marketed drugs and investigational agents have been evaluated for AH over decades, but none have proven consistently effective or received regulatory approval. Currently, a third of severe AH patients won't survive beyond three months. This patient community urgently needs a therapy that can improve standard of care and save lives.'.

和主要研究作者。”几十年来，许多市售药物和研究药物已被评估为AH，但没有一种被证明持续有效或获得监管部门的批准。目前，三分之一的重症AH患者无法存活超过三个月。这个病人社区迫切需要一种可以提高护理水平和挽救生命的疗法。”。

Norman Sussman

诺曼·苏斯曼

, 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.

DURECT首席医学官FAASLD博士评论道，“AHFIRM数据在如此受人尊敬的期刊上的发布突显了临床发现的重要性——我们很高兴与更广泛的科学和医学界分享详细结果。本文中的其他分析强调了患者人群和AH治疗方案的区域差异，包括从入院到治疗的时间以及肝移植的使用。

This comprehensive analysis has guided us in designing a robust Phase 3 trial protocol to focus on U.S. patients, with 90-day mortality as the primary endpoint.'.

这项综合分析指导我们设计了一个强大的3期试验方案，以美国患者为重点，90天死亡率为主要终点。”。

James E. Brown

詹姆斯·E·布朗

, 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.'.

DURECT总裁兼首席执行官D.V.M.补充道，“我们期待在即将进行的3期临床试验中进一步证明拉舒固醇的潜力。。我们计划在2025年启动试验，等待资金支持。”。

Key data highlights from the AHFIRM trial, include:

AHFIRM试验的关键数据亮点包括：

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 and 35% (p=0.124) in the 90 mg arm compared with placebo.

与安慰剂相比，30 mg和90 mg larsucosterol剂量均显示出降低90天死亡率的临床意义趋势，30 mg组死亡率降低41%（p=0.068），90 mg组死亡率降低35%（p=0.124）。

The reductions in mortality at 90 days were more pronounced in U.S. patients with reductions of 57% (p=0.014) in the 30 mg arm and 58% (p=0.008) in the 90 mg arm compared with placebo; computations for random sample analysis suggest that the U.S. results of larsucosterol treatment were unlikely to be an artifact of random chance..

与安慰剂相比，美国患者90天死亡率的降低更为明显，30 mg组降低57%（p=0.014），90 mg组降低58%（p=0.008）；。。

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.

90天时死亡率或肝移植主要终点的数值改善对于任一剂量的拉苏固醇均未达到统计学显着性。

Variations in time from hospitalization to first dose highlighted the importance of timely treatment in patients with severe AH.

从住院到首次给药的时间变化突出了严重AH患者及时治疗的重要性。

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.

在AHFIRM试验中，Larsucosterol似乎安全且耐受性良好，两组患者的治疗紧急不良事件（TEAE）和新发生的肝脏疾病严重并发症的数量与安慰剂组相似。

About the AHFIRM Trial

关于AHFIRM审判

AHFIRM was a Phase 2b randomized, double-blind, placebo-controlled, international, multi-center study conducted in subjects with severe alcohol-associated hepatitis (

AHFIRM是一项针对严重酒精相关性肝炎患者的2b期随机、双盲、安慰剂对照、国际多中心研究(

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ent (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).

耳鼻喉科（公司）。该研究由三组组成，招募了307名患者，每组约100名患者：（1）安慰剂，由标准护理组成，由研究人员决定是否使用甲基强的松龙胶囊；（2） larsucosterol（30毫克）；（3）larsucosterol（90毫克）。

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.

larsucosterol组的患者在没有类固醇的情况下接受了相同的支持治疗。主要结局指标是与安慰剂治疗的患者相比，用larsucosterol治疗的患者的90天死亡率或肝移植发生率，关键的次要终点是90天生存率。

The Company enrolled patients at clinical trial sites across the U.S., EU, U.K., and Australia. In November 2023, the Company announced topline data for the AHFIRM Trial. 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 and Breakthrough Therapy Designation for the treatment of AH.

该公司在美国、欧盟、英国和澳大利亚的临床试验地点招募患者。2023年11月，该公司宣布了AHFIRM试验的topline数据。美国食品和药物管理局（FDA）已授予拉舒固醇快速通道指定和突破性治疗指定，用于治疗AH，这反映了AH的危及生命的性质和缺乏治疗选择。

For more information, refer to ClinicalTrials.gov Identifier: NCT04563026..

有关更多信息，请参阅ClinicalTrials.gov标识符：NCT04563026。。

About Alcohol-associated Hepatitis (AH)

关于酒精相关性肝炎（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.

AH是一种急性形式的酒精相关性肝病（ALD），与长期大量饮酒有关，通常是在最近一段时间的饮酒增加（即暴饮暴食）之后。AH的典型特征是严重的炎症和肝细胞损伤，可能导致危及生命的并发症，包括肝衰竭，急性肾损伤和多器官衰竭。

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 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.

没有FDA批准的AH治疗方法，对1971年至2016年间发表的77项研究进行回顾性分析，其中包括8184名患者的数据，显示AH的总死亡率在28天时为26%，在90天时为29%，在180天时为44%。随后于2021年12月发表的一项全球研究包括3大洲11个国家的85个三级中心，前瞻性招募了2581名AH患者，终末期肝病（MELD）评分中位数为23.5，报告28天和90天的死亡率分别约为20%和31%。

Stopping alcohol consumption is necessary, but frequently not sufficient for recovery in many moderate (defined as MELD scores of 11-20) and severe (defined as MELD scores >20) patients, and therapies that reduce liver inflammation, such as corticosteroids, are limited by contraindications, have not been shown to improve survival at 90 days or one year, and have demonstrated an increased risk of infection.

停止饮酒是必要的，但对于许多中度（定义为MELD评分11-20）和重度（定义为MELD评分>20）患者以及减少肝脏炎症的疗法（如皮质类固醇）来说，停止饮酒通常不足以恢复。禁忌症的限制，尚未显示出可以改善90天或一年的生存率，并且已经证明感染风险增加。

While liver transplantation is becoming more common for ALD patients, including AH patients, the total number of such transplants is 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..

虽然包括AH患者在内的ALD患者的肝移植越来越普遍，但此类移植的总数相对较少，并且受到器官可用性的限制。肝移植的平均费用超过875000美元，患者需要终身免疫抑制治疗以防止器官排斥。。

About Larsucosterol

关于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).

Larsucosterol是一种内源性硫酸化氧固醇和表观遗传调节剂。表观遗传调节因子是调节基因表达模式而不改变DNA序列的化合物。DNA超甲基化是表观遗传失调的一个例子，导致转录组重编程和细胞功能障碍，并且已经在许多急性（例如AH）和慢性疾病（例如MASH）中报道过。

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.

作为DNA甲基转移酶（DNMT1，DNMT3a和3b）的抑制剂，larsucosterol抑制DNA甲基化，随后调节与应激反应，细胞死亡和存活以及脂质生物合成相关的细胞信号传导途径中涉及的基因的表达。这可能最终导致细胞存活率提高，炎症减轻和脂毒性降低。

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..

作为表观遗传调节剂，所提出的作用机制为开发用于治疗急性器官损伤和某些慢性疾病的larsucosterol提供了进一步的科学依据。。

About DURECT Corporation

关于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.

DURECT是一家晚期生物制药公司，率先开发针对失调的DNA甲基化的表观遗传疗法，以改变包括急性器官损伤在内的严重和危及生命的疾病的治疗。杜雷特的主要候选药物拉苏甾醇结合并抑制DNA甲基转移酶的活性，DNA甲基转移酶是AH患者中发现的升高并与高甲基化相关的表观遗传酶。

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.

Larsucosterol正在临床开发AH的潜在治疗方法，FDA已授予其快速通道和突破性治疗指定；MASH也在探索中。此外，波西米尔。

(bupivacaine solution) for infiltration use, a non-opioid analgesic utilizing the innovative SABER

（布比卡因溶液）用于渗透使用，一种利用创新SABER的非阿片类镇痛药

platform technology, is FDA-approved. For more information about DURECT, please visit

平台技术，是FDA批准的。有关DURECT的更多信息，请访问

www.durect.com

and follow us on X (formerly Twitter) at

并在X（以前的Twitter）上关注我们

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.

本新闻稿包含前瞻性声明，包括根据1995年《私人证券诉讼改革法案》的安全港条款所作的声明，涉及：我们计划进行拉鲁甾醇的3期临床试验，3期试验的能力，如果成功，支持NDA申请，2025年上半年我们资本要求的充分性以及拉鲁甾醇治疗AH和潜在其他适应症患者的潜在用途。

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 co.

实际结果可能与本新闻稿中包含的前瞻性声明中包含的结果存在重大差异，报告的结果不应被视为未来表现的指标。可能导致实际结果与预测结果不同的潜在风险和不确定性包括，未来的拉舒固醇临床试验被延迟或无法确认AHFIRM试验（包括地理或其他细分）或早期临床或临床前试验的子集分析结果，或未以统计学显着方式证明拉舒固醇的安全性或有效性的风险；我们没有筹集足够的资金来开始或完成AH患者的拉苏固醇的3期临床试验或继续资助我们的运营的风险，FDA或其他政府机构在批准拉苏固醇治疗AH之前可能需要额外的拉苏固醇临床试验的风险，突破性治疗指定不会加快FDA批准的过程，并且拉苏固醇可能永远不会被批准的风险；。

December 31, 2023

2023年12月31日

and quarterly report on Form 10-Q for the quarter ended

表10-Q中截止季度的季度报告

September 30, 2024

2024年9月30日

, under the heading 'Risk Factors.' These reports are available on our website

，标题为“风险因素”这些报告可在我们的网站上找到

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.

。本新闻稿中提供的所有信息均基于截至本新闻稿发布之日杜雷特可获得的信息，杜雷特不承担因未来事件或事态发展而更新此信息的义务，除非法律要求。

NOTE: POSIMIR

注：POSIMIR

is a trademark of Innocoll Pharmaceuticals, Ltd. in the U.S. and a trademark of DURECT Corporation outside of the U.S. SABER

是Innocoll Pharmaceuticals，Ltd.在美国的商标，也是DURECT Corporation在美国SABER以外的商标

is a trademark of DURECT Corporation. Other referenced trademarks belong to their respective owners. 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..

是DURECT Corporation的商标。其他引用商标属于其各自所有者。Larsucosterol是一种正在开发的研究药物候选药物，尚未获得美国食品和药物管理局或其他卫生部门的商业化批准。。

SOURCE DURECT Corporation

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