Dexlansoprazole

MALVERN, Pa., May 30, 2024 /PRNewswire/ -- Endo, Inc. ("Endo" or the "Company"), a newly formed entity that recently acquired (the "Acquisition") substantially all of the assets of Endo International plc ("EIP") as contemplated by EIP's plan of reorganization (the "Plan"), today made select first-quarter 2024 financial results for EIP available to investors. EIP's first-quarter financial results were in-line with its previously provided expectations. Endo is providing the following historical financial information of EIP because, from Endo's formation through March 31, 2024, it had no operations, business transactions or activities other than those incidental to its formation or taken in contemplation of the Plan (including the Acquisition). Endo had no other assets or liabilities during the periods presented in this release. The following historical financial information of EIP does not give effect to the transactions contemplated by the Plan or the application of fresh start accounting expected to apply to Endo's financial information beginning in the second quarter of 2024. EIP FIRST-QUARTER FINANCIAL PERFORMANCE (in thousands) EIP CONSOLIDATED FINANCIAL RESULTS Total revenues were $420 million in first-quarter 2024, a decrease of 19% compared to $515 million in first-quarter 2023. This decrease was primarily attributable to decreased revenues from the Generic Pharmaceuticals segment. Reported Net Loss in first-quarter 2024 was $154 million compared to reported Net Loss of $3 million in first-quarter 2023. This change was primarily due to increased expenses related to the Chapter 11 reorganization process and decreased revenues. Adjusted Net Income in first-quarter 2024 was $131 million compared to $193 million in first-quarter 2023. This change was primarily driven by decreased revenues. BRANDED PHARMACEUTICALS SEGMENT First-quarter 2024 Branded Pharmaceuticals segment revenues were $201 million compared to $198 million during first-quarter 2023. Specialty Products revenues increased 4% to $148 million in first-quarter 2024 compared to $142 million in first-quarter 2023. This change was primarily due to an increase in XIAFLEX® revenues, partially offset by a decrease in SUPPRELIN® LA revenues mainly driven by lower volumes. First-quarter 2024 XIAFLEX® revenues were $113 million, an increase of 17% compared to $97 million during first-quarter 2023 driven by increased net selling price and increased volumes. STERILE INJECTABLES SEGMENT First-quarter 2024 Sterile Injectables segment revenues were $98 million, a decrease of 3% compared to $101 million during first-quarter 2023. This decrease was primarily attributable to competitive pressure on a number of products and was partially offset by increased VASOSTRICT® and ADRENALIN® revenues driven by higher volumes. GENERIC PHARMACEUTICALS SEGMENT First-quarter 2024 Generic Pharmaceuticals segment revenues were $103 million, a decrease of 48% compared to $198 million during first-quarter 2023. This decrease was primarily attributable to competitive pressure on varenicline tablets, the generic version of Chantix®, and dexlansoprazole delayed release capsules, the generic version of Dexilant®, partially offset by increased revenues from lidocaine patch 5%, the generic version of LIDODERM®. INTERNATIONAL PHARMACEUTICALS SEGMENT First-quarter 2024 International Pharmaceuticals segment revenues were $17 million compared to $18 million during first-quarter 2023. CASH, CASH FLOW AND OTHER UPDATES As of March 31, 2024, EIP had approximately $641 million in unrestricted cash and cash equivalents. First-quarter 2024 net cash provided by operating activities was approximately $26 million compared to approximately $62 million net cash provided by operating activities during first-quarter 2023. This change was primarily driven by decreased revenues. 2024 FINANCIAL EXPECTATIONS Endo is providing financial guidance for the full-year ending December 31, 2024, which guidance includes EIP's financial results prior to the Acquisition. All expectations provided by Endo, which are unchanged from expectations previously provided by EIP, are forward-looking and actual results may differ materially and adversely from such expectations, as further discussed below under the heading "Cautionary Note Regarding Forward-Looking Statements." CONFERENCE CALL INFORMATION Endo will host a conference call to discuss this press release tomorrow, May 31, 2024, at 8:30 a.m. ET for registered holders of its debt and equity securities. There are three ways to join the call: Phone link to register and receive an automatic callback when conference call begins: Phone dial-in number with operator support: 800-836-8184 (U.S. and Canada toll-free) or 646-357-8785 Webcast: Please dial in 10 minutes prior to the scheduled start time. Dexilant® is a registered trademark of Takeda Pharmaceutical U.S.A., Inc. Chantix® is a registered trademark of Pfizer Inc. LIDODERM® is a registered trademark of Endo, Inc. FINANCIAL SCHEDULES The following table presents Endo International plc's unaudited Total revenues, net for the three months ended March 31, 2024 and 2023 (dollars in thousands): The following table presents unaudited Condensed Consolidated Statement of Operations data of Endo International plc for the three months ended March 31, 2024 and 2023 (in thousands): The following table presents unaudited Condensed Consolidated Balance Sheet data of Endo International plc at March 31, 2024 and December 31, 2023 (in thousands): The following table presents unaudited Condensed Consolidated Statement of Cash Flow data of Endo International plc for the three months ended March 31, 2024 and 2023 (in thousands): SUPPLEMENTAL FINANCIAL INFORMATION Non-GAAP Financial Measures To supplement the financial measures prepared in accordance with U.S. generally accepted accounting principles (GAAP), the Company provides certain financial information of Endo International in this release that are not prescribed by or prepared in accordance with GAAP. The Company utilizes these non-GAAP financial measures as supplements to financial measures determined in accordance with GAAP when evaluating operating performance and the Company believes that these measures will be used by certain investors to evaluate operating results. The Company believes that presenting these non-GAAP financial measures provides useful information about performance across reporting periods on a consistent basis by excluding certain items, which may be favorable or unfavorable, as more fully described in the reconciliation tables below. Despite the importance of these measures to management in goal setting and performance measurement, the Company stresses that these are non-GAAP financial measures that have no standardized meaning prescribed by GAAP and, therefore, have limits in their usefulness to investors. Because of the non-standardized definitions, non-GAAP adjusted EBITDA and non-GAAP adjusted net income (unlike GAAP net income and its components) may differ from, and may not be comparable to, the calculation of similar measures of other companies. These non-GAAP financial measures are presented solely to permit investors to more fully understand how management assesses performance. These non-GAAP financial measures should not be viewed in isolation or as substitutes for, or superior to, financial measures calculated in accordance with GAAP. Investors are encouraged to review the reconciliations of the non-GAAP financial measures used in this press release to their most directly comparable GAAP financial measures. However, the Company does not provide reconciliations of projected non-GAAP financial measures to GAAP financial measures, nor does it provide comparable projected GAAP financial measures for such projected non-GAAP financial measures. The Company is unable to provide such reconciliations without unreasonable efforts due to the inherent difficulty in forecasting and quantifying certain amounts that are necessary for such reconciliations, including adjustments that could be made for asset impairments, contingent consideration adjustments, legal settlements, gain / loss on extinguishment of debt, adjustments to inventory and other charges reflected in the reconciliation of historic numbers, the amounts of which could be significant. The tables below provide reconciliations of certain of the non-GAAP financial measures included in this release to their most directly comparable GAAP metrics. Refer to the "Notes to the Reconciliations of GAAP and Non-GAAP Financial Measures" section below for additional details regarding the adjustments to the non-GAAP financial measures detailed throughout this Supplemental Financial Information section. Reconciliation of Net Loss (GAAP) to EBITDA (non-GAAP) and Adjusted EBITDA (non-GAAP) The following table provides a reconciliation of Net loss (GAAP) to Adjusted EBITDA (non-GAAP) for the three months ended March 31, 2024 and 2023 (in thousands): Reconciliation of Net Loss (GAAP) to Adjusted Net Income (non-GAAP) The following table provides a reconciliation of the Endo International plc's Net Loss (GAAP) to Adjusted Net Income (non-GAAP) for the three months ended March 31, 2024 and 2023 (in thousands): Reconciliation of Select Other Adjusted Income Statement Data (non-GAAP) The following tables provide detailed reconciliations of select other income statement data for Endo International between the GAAP and non-GAAP amounts for the three months ended March 31, 2024 and 2023 (in thousands, except per share data): Notes to the Reconciliations of GAAP and Non-GAAP Financial Measures SEC Review Endo has confidentially submitted a draft registration statement with the U.S. Securities and Exchange Commission (the "SEC") to effectuate its previously announced goal of listing its common stock on a national stock exchange. The registration statement includes a description of Endo's business, financial and other information, some of which is included in this press release. Comments by the SEC on the registration statement may require modification or reformulation of the description of Endo's business. As a result, financial information that Endo presents in the future may differ in presentation or calculation from the information presented herein. This press release does not constitute an offer to sell or the solicitation of an offer to buy any securities. Any offers, solicitations or offers to buy, or any sales of securities will be made in accordance with the registration requirements of the Securities Act of 1933, as amended. About Endo Endo is a diversified specialty pharmaceutical company boldly transforming insights into life-enhancing therapies. Our passionate team members collaborate to develop and deliver these essential medicines. Together, we are committed to helping everyone we serve live their best life. Learn more at or connect with us on LinkedIn. Cautionary Note Regarding Forward-Looking Statements This release includes certain statements, claims, estimates, predictions and other information prepared and provided by Endo with respect to the anticipated future performance of Endo and its subsidiaries. Such statements include or are based on "forward looking statements" including, but not limited to, statements relating to financial expectations or guidance and any other statements that refer to expected, estimated or anticipated future results or that do not relate solely to historical facts. Statements including words such as "believes," "expects," "anticipates," "intends," "estimates," "plan," "will," "may," "look forward," "intends," "guidance," "future," "potential" or similar expressions are forward-looking statements. Because these statements reflect Endo's current views, expectations and beliefs concerning future events, they involve risks and uncertainties, some of which Endo may not currently be able to predict. Although Endo believes that these forward-looking statements and other information are based upon reasonable assumptions and expectations, readers should not place undue reliance on these or any other forward-looking statements and information. Actual results may differ materially and adversely from current expectations based on a number of factors, including, among other things, the following: the effects of the emergence of EIP's operating assets from the Chapter 11 financial restructuring process, including as it relates to the accounting for the effects of the Plan and the application of fresh start accounting; changes in competitive, market or regulatory conditions; changes in legislation or regulations; the ability to obtain and maintain adequate protection for intellectual property rights; the impacts of competition such as those related to XIAFLEX®; the timing and uncertainty of the results of both the research and development and regulatory processes; health care and cost containment reforms, including government pricing, tax and reimbursement policies; the performance including the approval, introduction and consumer and physician acceptance of current and new products; the ability to develop and expand our product pipeline and to continue to develop the market for XIAFLEX® and other branded or unbranded products; the effectiveness of advertising and other promotional campaigns; and the timely and successful implementation of any strategic priorities. Endo assumes no obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise, except as may be required under applicable securities laws. Copies of the Company's press releases and additional information about the Company are available at or you can contact the Company's Investor Relations Department at [email protected]. SOURCE Endo, Inc. SOURCE Endo, Inc.

同写意20岁庆！第五届全球生物医药前沿技术大会报名开启！“意”同创新，穿越周期。7月中旬，苏州金鸡湖畔，让我们与“新药写意人”一起为中国医药创新“同写意”！在创新药内卷逐渐加剧和仿制药竞价愈演愈烈的大环境下，改良型新药的研发成为热点之一，从2016年法规首次提出“改良型新药”后，相关政策、法规、技术要求等各个方面均快速发展，研发门槛也迅速提高。有创意的设计、有壁垒的技术、独到的销售优势等，都是改良型新药成功的要素。怎样在非临床/临床研究中，通过恰当的桥接和巧妙的设计，对预设的临床优势进行证明，成为改良型新药能否顺利报批的决定性要素之一，也是产品能否最终获得医患与市场认可的重要因素。本文综合了相关的法规、文章、审评文件，并以国内外获批产品为案例，对改良型新药的非临床和临床研究策略进行了探讨。1国内改良型创新现状在2016年法规首次明确“改良型新药”后，其俨然成为新的研发风口[1]。但获批产品中市场表现优异的不多，纵观美国505(b)(2)近40年的发展也可见：只有具备临床优势，且证明了自身优势的改良型产品，才能最终获得市场认可。因此，怎样合理制定非临床和临床研究策略，在最大程度保留改良型新药“成本低、周期短”研发红利的同时证明产品临床优势，成为其开发的真正挑战。CDE颁布的相关法规、指导原则，以及发表的文章均着力于对其非临床和临床研究策略进行指导，对其整理如图1所示。图1：CDE相关法规/指导原则/发表文章中非临床临床研究要点梳理随着行业的迅速发展，证明产品临床优势成为改良型新药研发的重点，为此，需要在临床研究中进行合理的桥接和巧妙的设计，表1为2023年获批的改良型新药（2类新药）及其临床研究策略：表1 2023年化学药改良型新药获批情况如上表所示，在2023年无2.1类产品获批；获批的2.4类产品主要是新药公司对其产品的适应症拓展；在2.2和2.3类获批的产品中，70%完成了安全性和有效性研究，力求通过临床试验证明产品预设的临床优势。合理的非临床和临床研究策略，能在节省改良型新药研究成本、加快研发进度的同时，力求以实验数据和临床效果来证明其优势。2非临床研究参考国内外相关文献[2][3][4]，对2类新药的非临床研究内容进行了梳理，如表2所示。表2 改良型新药非临床研究示例[2][3][4]如上表，非临床研究的内容需结合改良前后的暴露途径、体内PK差异、给药方案等进行综合评估。12.1 类（已知化合物的光学异构体、成酯/盐、改酸/碱基等）化药分类2.1类改良通常是针对已知化合物分子进行的改良，包括拆分为光学异构体、开发为前药、成盐等，通常需要完成的非临床研究内容包括：PK/ADME研究，必要的有效性研究，单次、重复给药毒性研究，必要的发育毒性、遗传毒性研究等。右兰索拉唑是兰索拉唑的右旋异构体，以505(b)(2)途径在美国获批，其FDA审评文件中显示本品非临床研究内容包括：①药效学：与消旋体、左旋体进行了体外和体内对比，证明了右旋体的有效性优势。②非临床药代研究：进行了右旋兰索拉唑的PK/ADME研究。③毒理学：进行了一项4周的大鼠给药毒性试验作为“桥接”，对比了右旋体与左旋体、消旋体的毒性，在伴随毒代动力学试验中同时评价了右旋兰索拉唑是否会向其左旋体转化。此外，还进行了右旋体的2项13周（大鼠和犬）重复给药毒性试验，1项兔胚胎—胎仔发育毒性试验，以及标准组合的遗传毒性试验[3][5] 。22.2 类（新剂型、新给药途径及新工艺等针对制剂的改良）针对2.2类改良，非临床研究可参考FDA指导原则[6]：①单次给药毒性试验和/或重复给药毒性试验。②改良前后产品的PK/ADME全面对比，并根据结果评价已有的毒性研究信息是否充分，并进行其他必要的非临床研究。FDA《CY 2023 CDER Drug and Biologic Calendar Year Approvals》中公布2023年CDER共批准113款NDA，其中以505(b)(2)途径批准的有58款，表3为其中几款剂型和处方等改良的案例。表3  FDA获批剂型/处方等改良的非临床研究内容示例如上表所示，2.2类的改良大多需完成非临床PK研究、单次/重复给药毒性等研究，以FDA批准的OPVEE®为例，该产品将盐酸纳美芬注射剂Revex®改为吸入制剂，FDA审评文件公布了其非临床研究内容，如图2所示[7]。图2 FDA审评文件中OPVEE®所完成的非临床研究[7]如上图所示，OPVEE®通过PK研究桥接了被改良产品Revex®的生殖和发育毒理数据；在鼠和犬中进行了28天重复给药毒性研究，对本品局部和系统毒性进行了评估；针对纳美芬还增加了对心脏和呼吸系统的安全性考察。此外，参考相关文献法规可知，在2.2类改良产品的非临床研究中，必要时需进行附加的毒性试验，如安全药理学试验、生殖毒性试验等。32.3 类（新的复方）针对2.3类的改良，一般应对处方中各单药的联合用药经验、作用机制、代谢特征等进行综合考虑，预估药物-药物相互作用的可能，评估可能的安全性风险并进行相应的非临床研究[3]。以2023年FDA批准的COMBOGESIC®为例，该产品为乙酰氨基酚和盐酸布洛芬的复方片，由于作用机制清晰、临床联用数据充分，经评估后认为无需进行额外的非临床毒理研究，但出于一些文献中对两者联用后胃肠道和/或肾毒性的报道，进行了两项相关的非临床毒理考察[8]。42.4 类（新适应症）2.4类为新适应症的开发，需对已有的非临床／临床安全性信息进行回顾分析，判断是否支持新的适应证[3]。在可能涉及用法用量增加、用药时间延长、用药人群改变等情况时，应评价原有毒性信息是否足以支持这些改变，必要时需追加相应的非临床研究。综上，非临床研究的内容需根据改良前后产品的差异进行制定，包括给药途径、体内药代等方面的差异；也包括杂质情况、新辅料使用情况等方面的差异。例如2023年获批的ATORVALIQ®出于改良后产品新杂质的原因，进行了相应的毒性研究。3临床研究据今年颁布的《化学药改良型新药临床药理学研究技术指导原则》及相关文献，对2类新药的临床研究内容梳理。12.1类2.1类改良应开展单次/多次给药PK研究、与被改良药PK对比、剂量比例关系、食物影响等研究及可能情况下的PK/PD研究[9]。比如，琥珀酸去甲文法拉辛改良为去甲文法拉辛，仅是盐型的简单改变，预期不会对PK行为和体内安全性/有效性造成影响，因此改良后仅完成了与被改良药的BE对比，桥接了安全性/有效性数据。但是，当改良后产品PK特征改变，现有数据不足以证明产品安全/有效时，需完成相应研究，如CDE批准的左奥硝唑氯化钠注射液，该产品将奥硝唑开发为其左旋异构体，研究内容包括：①单次和连续给药PK研究、耐受性研究；②与被改良产品的PK对比研究，结果显示左奥硝唑在体内未发生异构体转化；改良前后的代谢产物及其水平相近；左奥硝唑的Cmax与被改良产品相近，但改良前后可能存在消除差异，左奥硝唑消除更快。③以被改良药为阳性对照，评价了左奥硝唑氯化钠注射液的有效性及安全性。22.2 类参考505(b)(2)产品，在剂型、给药途径等改良后临床研究内容如图3[2]。图3 不同类型505(b)(2)获批产品临床研究内容如上图，大多数产品剂型、处方等改良后需完成单剂量、多剂量BA/BE、食物效应等研究，参考相关法规，可以将2.2类改良的临床策略分为以下两类：（1） 不改变PK特征如普通片、分散片、口溶膜等剂型之间的改变，通常不会改变产品PK特征，CDE公布了该类产品的审评信息，其临床研究策略如表4所示。表4 国内已获批2.2类中PK特征不改变的产品临床研究内容如上表所示，在PK行为不发生改变时，可通过与被改良药品进行BA/BE研究，桥接现有安全/有效性数据，并豁免相应研究。此外，还需要考虑对改良后的临床优势进行证明，以口溶膜为例，2022年后批准的口溶膜均要求完成无水吞服方式下的BE研究和口腔内溶解时间、口感等方面的考察。（2）改变PK特征通过改善药物的体内释放速度、吸收程度、组织分布等PK特征，可能获得顺应性、安全性或有效性等方面的临床优势。对该类制剂需选择适宜的给药方案开展与被改良药物的PK对比研究、剂量比例关系、食物影响等研究，以及可能情况下的PK/PD研究，必要时需完成安全性/有效性评价。CDE公布的相关药品审评信息如表5所示。表5  国内已获批2.2类中PK改变的产品临床研究内容如上表所示，兰索拉唑碳酸氢钠胶囊的研究内容为：①单次和多次给药的PK研究，证明本品比被改良药肠溶胶囊具有更早的达峰时间、更高的药物峰浓度；②对比本品和被改良药多次给药下的PK行为，证明两者具有相似的稳态药代动力学参数（AUC0-τ、AUC0-∞、 Cavg,ss）；③通过PK-PD研究证明了本品的药效指标主要与AUC相关；④最终基于本品与被改良药AUC等效，抑酸作用相关的PD指标相似，认为二者治疗等效，接受以PK/PD和生物等效性试验结果支持本品桥接被改良药已批准适应症的有效性结果。紫杉醇胶束注射液是对其注射液的改良，采用单次静脉给药考察了不同剂量下的PK特征，初步评估了安全性、耐受性，剂量-暴露量关系，并确认了后续临床研究给药方案；通过安全性和有效性研究，证明了有效性/安全性。32.3类新复方制剂应提供充分PK研究、相互作用（DDI）研究、剂量-暴露 -效应分析等数据，为确定新复方制剂的配比、给药剂量、 给药间隔等提供依据[9]。CDE在4月公布了阿达帕林克林霉素凝胶的临床研究内容：①考察了本品和改良前单药盐酸克林霉素凝胶、阿达帕林凝胶的药代动力学特征，与单方相比，复方中盐酸克林霉素的Cmax和AUC0-72均显著提高；②对部分受试者开展了PK研究和药物暴露研究，探索了本品不同配方的有效性和安全性，初步判断最优的配方组；③在III期临床研究中，使用前期摸索出的最佳配方和给药方案，证明了本品对比单药的疗效，证明本品疗效更好。42.4类对此类改良型新药，通常以关键性临床研究支持新增适应症申请，应提供新增适应症拟定用法用量的选择依据，如剂量探索研究和/或剂量-暴露-效应分析等[9]。— 小结 —  改良型新药已成为当前研发的热点方向之一，在行业迅速发展的同时，研发门的槛也在逐渐提高，在CDE《2023年度药品审评报告中》显示：2023年改良型化药IND申请量同比增长27.54%，NDA建议批准量却同比减少20.41%。纵观美国505(b)(2)近40年的发展和国内近年的发展形式可见，忽略了真正的临床需求，过度追求短周期、少投入的改良，最终难以获得可观的市场回报，甚至无法获批。只有以解决临床需求为目标，在非临床和临床研究中进行恰当的桥接，巧妙的设计，才能在最大程度保留2类改良新药“成本低、周期短”红利的同时，真正证明产品的临床优势。参考文献：（上下滑动查看更多）1. 吕奕,张怡萌,等. 我国化学药改良型新药申报审批情况分析与思考[J]. 中国新药杂质,2023,32(15): 1523-1530.2. Freije I, Lamouche S, Tanguay M. Review of drugs approved via the 505(b)(2) pathway: Uncovering drug development trends and regulatory requirements. Therapeutic Innovation & Regulatory Science. 2020;54(1): 128-138.3. 戴学栋,孙涛,等. 改良型新药非临床研究的一般考虑及需要关注的问题[J].中国新药质,2017,26(18): 2121-2127.4. 孙昱,孙国祥,等. FDA 505(b)(2)改良型新药的申报情况对中药改良型新药的启发思考对中药改良型新药的启发思考[J]. 中南药学,2021,19(3): 369-375.5. FDA. Dexlansoprazole.Pharmacology review.https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022287s000_PharmR.pdf6. FDA.Nonclinical Safety Evaluation of Reformulated Drug Products and Products Intended for Administration by an Alternate Route.https://www.fda.gov/regulatory-information/search-fda-guidance-documents/nonclinical-safety-evaluation-reformulated-drug-products-and-products-intended-administration.7. FDA. NALMEFENE HYDROCHLORIDE. NON-CLINICAL REVIEW(S).https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/217470Orig1s000PharmR.pdf8. FDA. ACETAMINOPHEN; IBUPROFEN.NON-CLINICAL REVIEW(S).https://www.accessdata.fda.gov/drugsatfda_docs/nda/2024/209471Orig1s000PharmR.pdf9.CDE.化学药改良型新药临床药理学研究技术指导原则(试行).https://www.cde.org.cn/main/news/viewInfoCommon/25f498093f32286f0f31dbc4d1c8bb43更多优质内容，欢迎关注↓↓↓