Methylprednisolone

近日，上海不少渐冻症患者家属反映，他们所依赖的进口药物利鲁唑片，又叫"力如太"，在市区的多家医院出现了缺货现象，患者和家属都忧心如焚。渐冻症是一种不可逆的致死性运动神经元病，主要症状为四肢和躯干肌肉表现进行性加重的肌肉无力和萎缩，逐渐失去运动功能，就像被“冻住”一般。该病一般进展迅速，半数以上患者确诊后平均生存时间为3-5年，最后多死于呼吸肌无力导致的呼吸衰竭。据估计，ALS在全球范围内的发病率约为十万分之二。渐冻症与阿尔茨海默症一样，至今发病机制尚不明确，这也导致ALS新药的研发失败率高，治疗药物十分有限。目前我国获批用于治疗ALS的药物只有利鲁唑和依达拉奉。利鲁唑是一种苯并噻唑衍生物，可阻断中枢神经系统中的谷氨酸能神经传递。据了解，利鲁唑片市场价格，3689元一盒，每盒包含56片，一般可供患者服用28天。目前，由于这款药物已经纳入医保，患者每月仅需自付千元左右。  由于渐冻症患者总数较少，不少市区医院都没有进货这款药物，原来市中心也只有华山、中山等医院有所备货。但从今年2月份以来，市区的这几家医院也都配不到这款药品，患者家属陷入了困境。一位渐冻症患者家属在接受采访时说：“我问过的，说现在这个药没有，华山、六院我都问过，六院也是三甲医院都没有，中山也没有。他们理由就是现在这个药没有，要么吃国产。”尽管控制渐冻症的药物中也有国产仿制药，但多数患者和家属出于对药物效果的考虑和对原用药品的信任，仍然坚持选择“力如太”。记者从患者处了解到，进口药和国产仿制药的一大区别在于，进口药入喉咙即化，而国产药融化的速度并没有那么快，这看似很细微的差别，对于吞咽功能逐渐丧失的渐冻症患者来说，却至关重要。类似的情况也发生在了嘉定的过先生身上，他的老伴2021年10月被确诊为渐冻症，依赖“力如太”控制病情。医院药房告诉过先生，因为批号不对，药房进不了。由于渐冻症患者行动不便，上海有一批志愿者专门为他们无偿服务，帮他们配药，而医院药房的说法，一些志愿者在代配药时也有所耳闻。   志愿者许先生回忆，这款药物未进医保时单盒价格为4300多元，进医保后单盒价格从3800多元一路跌至3600元左右，患者承担的个人自付部分根据不同情况盒在900多元至1300多元不等。记者走访，探寻断货原因记者后续又致电了12393，医疗保障服务热线，该服务热线工作人员查询后透露，今年三、四月份，中山和华山医院曾进货过”力如太“这款药物，但是量非常小。倒是一家位于松江的养志康复医院，一直持续进货至今，进货量也比较稳定。记者走访同济大学附属养志康复医院了解到，他们是在阳光医药采购平台进货，且从未间断。记者又走访了售有“力如太”的两家药店，两家药店的工作人员透露，目前在这两家药店也可以买到“力如太”，但库存不多。其中一家药店，国药关爱大药房工作人员告诉记者，目前“力如太”是可以走医保的，但是要提前预定，药房这边订货。“因为这个药现在用得少，销量少，备的货也少。我们也找了很久才找到这个供货商才进到的，而且也属于提前打过招呼给他备的货，后期要用的话，提前一周跟我联系，我这边帮你进。”多种进口药都曾出现过断货或供货不足其实，除了“力如太”出现断供外，近年来，辉瑞的“美卓乐、”默沙东的“息宁”、施贵宝的“格华止”、吉利德的“韦瑞德”等进口药也都在中国出现过断供或是供货不足的情况。关于原研厂家断货，有人分析研究后总结出以下两大原因：一、企业主动断货。集采后，医院会首先保证中选品种的用量，且因为价格悬殊实在太大，原研企业可能会选择主攻院外市场，例如零售药店或者医药电商。同时，企业会提前战略调整生产线，减少产能，将生产线改造为利润更多的产品。   二、医院主动断货。集采后，医院必须要在保证中选品种的用量的前提下，才能考虑未中选品种。为了更好的推进带量采购，可能会在原研药用完之后，就暂时先不进货了。医药产业是关系国计民生的重要产业，如何提高药物的可及性，围绕以“患者价值为中心”让患者买到合适自己的药，需要在医保控费、药物临床价值和企业合理利润中找到均衡。              撰文 | Anna.An编辑 | Swagpp● 平时熬的夜竟能用周末补上！南京医科大学最新：周末补觉，患心血管疾病风险降70%！但要注意这2点● 震撼！医生质疑：我们院长竟然是文学专业的、书记空降的，外行领导内行，能指望他们做啥？院领导必须临床出身吗？中国院长画像告诉你答案● 重磅！5次问鼎NEJM，吴一龙教授团队或将改写全球指南！ALK阳性NSCLC的辅助治疗显著提高患者生存率版权说明：梅斯医学（MedSci）是国内领先的医学科研与学术服务平台，致力于医疗质量的改进，为临床实践提供智慧、精准的决策支持，让医生与患者受益。欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。点击下方「阅读原文」 立刻下载梅斯医学APP！

- Ongoing Communication with FDA to Align on Next Steps for Larsucosterol in Alcohol-Associated Hepatitis - Webcast of Earnings Call Today, March 27th at 4:30 p.m. ET CUPERTINO, Calif., March 27, 2024 /PRNewswire/ -- DURECT Corporation (Nasdaq: DRRX) today announced financial results for the fourth quarter and year ended December 31, 2023 and provided a business update. "We remain enthusiastic about the improvement in 90-day mortality demonstrated in our Phase 2b AHFIRM clinical trial and are communicating with the U.S. Food and Drug Administration (FDA) about the design of a confirmatory Phase 3 trial to support the potential approval of larsucosterol as a treatment for alcohol-associated hepatitis (AH)," stated James E. Brown, D.V.M., President and CEO of DURECT. "Larsucosterol could be the first FDA-approved treatment to address AH, a highly lethal condition that results in approximately 158,000 hospitalizations in the U.S. annually with a 30% mortality rate at 90 days." Business Update: In November 2023, DURECT announced topline data from the AHFIRM trial that showed a compelling efficacy signal in favor of larsucosterol in the key secondary endpoint of mortality at 90 days. Both the 30 mg and 90 mg larsucosterol doses demonstrated clinically meaningful trends in reduction of mortality at 90 days 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. 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. 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. Larsucosterol appeared safe and well tolerated in the AHFIRM trial with fewer treatment-emergent adverse events (TEAEs) in the larsucosterol arms compared with placebo. DURECT is in ongoing communications with the FDA to align on next steps for the development of larsucosterol, including the design for a pivotal Phase 3 clinical trial in AH. DURECT plans to provide an update in the second quarter of 2024. In March 2024, DURECT announced that it entered into a co-marketing and collaboration agreement with Charles River Laboratories for the ALZET® Osmotic Pumps Portfolio and Associated Product Line in the U.S. and Canada. Charles River Research Models & Services (RMS) sales and marketing teams will collaborate with DURECT to jointly market and commercialize the ALZET product line to existing and new customers in the pharmaceutical industry and academic laboratories over a multi-year period. Financial Highlights for Q4 and Full Year 2023: Total revenues were $2.7 million and net loss was $1.4 million for the three months ended December 31, 2023 compared to total revenues of $3.3 million and net loss of $10.5 million for the three months ended December 31, 2022. Total revenues were $8.5 million and net loss was $27.6 million for the year ended December 31, 2023, compared to total revenues of $19.3 million and net loss of $35.3 million for the year ended December 31, 2022. As of December 31, 2023, cash, cash equivalents and investments were $29.8 million, compared to cash, cash equivalents and investments of $43.6 million at December 31, 2022. Debt as of December 31, 2023 was $16.7 million, compared to $21.2 million as of December 31, 2022. Earnings Conference Call and Webcast We will host a conference call today at 4:30 p.m. Eastern Time/1:30 p.m. Pacific Time to discuss fourth quarter and 2023 results and provide a corporate update: Wednesday, March 27 @ 4:30 p.m. Eastern Time / 1:30 p.m. Pacific Time A live audio webcast of the presentation will be also available by accessing DURECT's homepage at and clicking "Investors." If you are unable to participate during the live webcast, the call will be archived on DURECT's website under "Event Calendar" in the "Investors" section. 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 sa Fety and eff Icacy of la Rsucosterol treat Ment (AHFIRM). The study was comprised of three arms and enrolled 307 patients, with approximately 100 patients in each arm: (1) SOC, which consists of 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 was the 90-Day incidence of mortality or liver transplantation for patients treated with larsucosterol compared to those treated with SOC. 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, as discussed above. 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. For more information, refer to ClinicalTrials.gov Identifier: NCT04563026. About Alcohol-associated Hepatitis (AH) AH is an acute form of alcohol-associated liver disease (ALD), associated with long-term heavy intake of alcohol and often occurs after a recent period of increased alcohol consumption (i.e., a binge). AH is typically characterized by severe inflammation and destruction of liver tissue (i.e., necrosis), 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 a total of 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. 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. While liver transplantation is becoming more common for ALD patients, including AH patients, the total number of such transplants is still 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. 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 found to be associated with many acute (e.g., AH) or 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 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 FDA has granted a Fast Track 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 the United States. For more information about DURECT, please visit and follow us on X (formerly Twitter) at . 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 for larsucosterol to demonstrate a reduction in mortality or liver transplant in patients with AH and to save lives, our ability to clarify with the FDA the design of the Phase 3 clinical trial of larsucosterol for AH, the potential FDA or other regulatory approval of larsucosterol for the treatment of AH, the potential to develop larsucosterol for AH, MASH 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 future clinical trials of larsucosterol 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, 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 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 quarterly report on Form 10-Q for the quarter ended September 30, 2023 and annual report on Form 10-K for the year ended December 31, 2023, when filed, under the heading "Risk Factors." These reports are available on our website under the "Investors" tab and on the SEC's website at . 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 U.S. and a trademark of DURECT Corporation outside of the U.S. SABER® 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. SOURCE DURECT Corporation