ACE

☝ 点击上方 一键预约 ☝   最新最热的医药健康新闻政策作为被纳入国家带量采购（VBP）较多的降压药类别，以缬沙坦、氯沙坦、厄贝沙坦氢氯噻嗪等为代表的肾素-血管紧张素系统（RAS）药物*近年来占据较大的份额。根据法伯全渠道数据显示，2022年这类药物在中国医疗机构*的销售规模超210亿元，在整体降压药市场的占比仅次于钙通道阻滞剂（CCB），达到37.2%，其中又以“沙坦”类单一及联合用药主导市场。补充说明*本文所述的肾素-血管紧张素系统药物市场范围（按照药物解剖学、治疗学及化学分类法ATC2编码）：C09；*中国医疗机构：包括两个医院渠道（城市医院、县域医院）和两个基层医疗机构渠道（社区卫生中心、乡镇卫生院）。总规模达212亿，由“沙坦”类药物主导肾素-血管紧张素系统（renin-angiotensin system，RAS）抑制剂是心肾血管疾病的重要治疗药物，主要包括以依那普利、贝那普利等为代表的血管紧张素转换酶抑制剂（ACEI），和以氯沙坦、缬沙坦等为代表的血管紧张素II拮抗剂（ARB）等。根据法伯全渠道数据显示，2022年我国总体医疗机构RAS类药物销售额达212.2亿元，同比降低12.5%，2021-2022年城市医院、县域医院、社区卫生中心和乡镇卫生院四个渠道的销售额降幅与整体降幅一致，渠道占比较为稳定，其中城市医院份额最高（图1）。图1-2021-2022年全部医疗机构RAS药物市场总规模及渠道分布数据来源：法伯全渠道数据值得关注的是，在整体RAS市场中，有超过80%的份额被“沙坦”类单一及联合用药占据，尤其是各类联合用药，2022年销售额超100亿元，占比达51.8%（图2）。图2-2022年全部医疗机构各类RAS药物销售额及占比数据来源：法伯全渠道数据这类药物也“霸占”了RAS市场TOP10分子的全部席位。根据法伯全渠道数据显示，2022年在总体医疗机构排名前四的全部为“沙坦”类联合用药，其中沙库巴曲缬沙坦和氯沙坦氢氯噻嗪的销售额超23亿元。此外，目前头部分子中的绝大部分已被纳入历次VBP（图3）。图3-2022年全部医疗机构RAS药物市场TOP10分子及规模占比数据来源：法伯全渠道数据七成已被集采，企业多渠道布局成常态如上所述，作为用药患者规模较大且市场竞争十分充分的领域，RAS类药物的头部品种已相继进入VBP。法伯数据显示，在2022年总体医疗机构RAS市场中，第1-9批VBP品种份额占70%左右，均为口服常释剂型，涉及到的原研企业主要包括赛诺菲、诺华、欧加隆、第一三共等，大多原研并未中标（图4）。图4-国家集采RAS药物品种及2022年在全部医疗机构销售额占比数据来源：法伯全渠道数据在政策利好广阔市场发展的背景下，近年来内外资企业进行多渠道布局已成为常态。整体而言，目前RAS类药物市场由内资企业主导，其不仅在四个销售渠道的市场占比均胜于外资，2022年的增速也优于外资（图5）。图5-2022年各渠道RAS类药物市场内外资企业销售额占比数据来源：法伯全渠道数据具体来看，根据法伯全渠道数据显示，2022年诺华在两个医院渠道销售额问鼎，而两个基层医疗机构渠道则是华海药业位居榜首，在四个渠道都进入TOP5的企业仅华海药业一家，可谓在该药物领域进行多渠道布局成绩斐然的内资企业（表1）。表1-2022年四个渠道RAS类药物市场销售额TOP10企业数据来源：法伯全渠道数据诺华4个原研产品落标，受VBP冲击较大作为涉及最多VBP降压药品种的原研外资企业之一，诺华旗下的缬沙坦（商品名：代文）、缬沙坦氨氯地平（商品名：倍博特）、缬沙坦氢氯噻嗪（商品名：复代文）、贝那普利（商品名：洛汀新）相继在第3-5批VBP（分别已于2020年11月、2021年4月和9月落地执行）落标。根据法伯全渠道数据显示，2022年这四个品种在总体医疗机构的销售额均明显下降（图6）。图6-部分诺华降压药品种总体医疗机构市场销售额变化22vs21数据来源：法伯全渠道数据以贝那普利为例，该药物为一款血管紧张素转换酶抑制剂（ACEI），由诺华制药研发，最早于1990年在欧洲上市。2019年，信立泰药业的10mg和5mg盐酸贝那普利片（商品名：信达怡）通过仿制药一致性评价，系国内首家过评；次年，上海医药子公司上海新亚药业的盐酸贝那普利片通过仿制药一致性评价。根据法伯全渠道数据显示，直到2021年，贝那普利在总体医疗机构超60%的份额仍被原研诺华占据，其余市场由上海医药、信立泰和地奥制药瓜分。而随着原研在第5批VBP落标以及信立泰和新亚药业的中标，到2022年，贝那普利的市场规模被“腰斩”，两家中标仿制药企快速抢占了原研的份额。分渠道来看，发现诺华仅在城市医院和社区卫生中心占比较高，而信立泰和上海医药在整体份额基本持平的情况下，前者在更加下沉的县域医院和乡镇卫生院颇具优势，后者则是四个渠道“并驾齐驱”，占比相当（图7）。图7-2021-2022年全部医疗机构贝那普利市场规模及企业渠道分布数据来源：法伯全渠道数据华海药业拥抱集采红利，加码多渠道布局内资企业方面，在RAS领域领衔市场的无疑是华海药业，作为本土心血管类制药龙头，华海药业在业界有着“普利专家”、“沙坦之王”的称号，旗下厄贝沙坦片、福辛普利那片、厄贝沙坦氢氯噻嗪片、氯沙坦钾片、奥美沙坦酯氢氯噻嗪等重磅降压药产品皆已在国内获批上市。公司自首轮“4+7”集采就开始积极参与竞标，并借助集采红利快速实现新产品上量和在国内市场份额的提升。渠道方面，公司坚持销售渠道裂变战略，构建多元化的销售结构，全面推进市场下沉。在产品力和销售力双轮驱动之下，根据法伯全渠道数据显示，2022年华海药业在全部医疗机构RAS市场排名仅次于诺华，稳居第二，销售占比达11%（表2）。表2-2022年总体医疗机构RAS类药物市场销售额TOP10企业数据来源：法伯全渠道数据从TOP10企业的渠道销售额分布也能明显看出，外资企业更加重视对城市医院的布局，而基本“放弃”了乡镇卫生院渠道，但大部分内资企业则是加码布局广阔市场渠道，尤其是华海药业、福元医药、华润双鹤和上海医药，在两个基层医疗机构市场的份额均超过50%。图8-2022年总体医疗机构RAS类药物市场头部企业及渠道分布数据来源：法伯全渠道数据新药增速迅猛，“应采尽采”或将持续在RAS药物市场，除了陆续被纳入VBP的老药，还有部分颇具潜力的新药值得关注。根据法伯全渠道数据显示，2022年在总体医疗机构RAS市场销售额最高以及增速最快的药物均在近几年上市。其中，以超20亿元市场规模问鼎的沙库巴曲缬沙坦（商品名：诺欣妥）由诺华原研，是首个血管紧张素受体脑啡肽酶抑制剂（ARNI），自2021年6月获批用于治疗原发性高血压后迅速跻身于TOP降压药前列，有效缓解了诺华在该药物领域由VBP带来的冲击，使其在总体医疗机构RAS市场依旧稳居第一。图9-2022年全部医疗机构RAS市场各分子规模及增速表现数据来源：法伯全渠道数据另外值得关注的是，美阿沙坦/阿齐沙坦虽然市场占比不高，但是在2022年的销售额增速十分瞩目（图9）。公开信息显示，自1995年奥美沙坦研发成功（2002年上市）后，新型ARB类药物的研发便陷入停滞，直到2011年由日本武田制药研发美阿沙坦钾获得美国FDA批准上市，成为最新且降压效果最强的“沙坦”类药物。美阿沙坦钾是一种前体药物，在口服吸收后可迅速转化为活性成分阿齐沙坦，后者在多种组织中可通过选择性阻断血管紧张素II与AT1受体的结合而阻断血管紧张素II的作用。目前，美阿沙坦钾片只有原研武田的易达比于2021年1月在我国获批上市，阿齐沙坦虽然原研未进口国内，但是恒瑞医药已在2021年申报3类仿制拿下首仿。根据法伯全渠道数据显示，截至2022年底，美阿沙坦、阿齐沙坦分别只有武田和恒瑞开始销售，且处于市场开拓期的阿奇沙坦市场增速较快。作为脱颖而出的降压新药，美阿沙坦钾和阿齐沙坦均已通过谈判被纳入国家医保，未来前景可期。此外，根据法伯此前盘点，目前RAS药物领域中尚未纳入VBP的沙库巴曲缬沙坦口服常释剂型和替米沙坦氢氯噻嗪口服常释剂型，已经满足竞争格局≥5家（点击相关阅读），数据显示，2022年这两类药物在总体医疗机构RAS市场的销售额占比超13%（图10），若未来纳入化药集采，又将掀起怎样的波澜，我们拭目以待。图10-2022年全部医疗机构RAS市场各批次VBP品种占比数据来源：法伯全渠道数据（来源:法伯科技）药闻康策新媒体矩阵微信公众号点击下方  一键关注  【免责声明】1.“药闻康策”部分文章信息来源于网络转载是出于传递更多信息之目的，并不意味着赞同其观点或证实其内容的真实性。如对内容有疑议，请及时与我司联系。2.“药闻康策”致力于提供合理、准确、完整的资讯信息，但不保证信息的合理性、准确性和完整性，且不对因信息的不合理、不准确或遗漏导致的任何损失或损害承担责任。3.“药闻康策”所有信息仅供参考，不做任何商业交易或医疗服务的根据，如自行使用“药闻康策”内容发生偏差，我司不承担任何责任，包括但不限于法律责任，赔偿责任。欢迎转发分享、点赞、点在看

When the Food and Drug Administration expanded approval of Novo Nordisks weight loss medicine Wegovy to also protect heart health, the Danish drug giant had already made a pipeline commitment to developing new cardiovascular treatments.The March 8 approval was followed by news this week that Novo plans to buy German cardiovascular specialist Cardior Pharmaceuticals for north of $1 billion. The heart is back, Cardior CEO and co-founder Claudia Ulbrich told PharmaVoice. Its back for venture capital, and its back for the pharma industry.As revenue from Wegovy sales pour in, Novo Nordisk is in position to bolster its pipeline further. The deal to buy Cardior, whose lead candidate CDR132L is a RNA-based treatment for heart failure, serves that purpose.Cardior is a 2016 spinout from Germanys Hannover Medical School, building on the work of Professor Thomas Thum, now the companys chief scientific and medical officer. Rather than turning to messenger RNA, Cardiors approach makes use of non-coding RNAs that arent translated into proteins, but regulate processes like cardiovascular function, Ulbrich said. CDR132L is an antisense oligonucleotide.Overall, the compound targets heart failure, and under this joint collaboration, we can address a large patient population, Ulbrich said.The cardiovascular drug field hasnt advanced as quickly in recent decades as has oncology and immunology. Over the last 20 years, we haven't really seen innovation in the cardiovascular space we had only symptomatic treatments [like] ACE inhibitors, beta blockers or diuretics, Ulbrich said.GLP-1 drugs like Wegovy, and their ability to reduce cardiovascular risk, give physicians new options for certain people and could lay the foundation for new combinations.It's too early to state whether there is potential for our drug to be a combination product because we have a unique and completely different mode of action, Ulbrich said. But Novo is clearly striving to strengthen its pipeline in cardiovascular disease coming from diabetes and obesity.Novo said in a statement that the acquisition is an important step forward for the company to establish a presence in cardiovascular disease. The biotech has invested in other pipeline assets as well, including a $1.3 billion dollar investment for a hypertension drug developed by KBP Biosciences last October. Across Novos pipeline, the company is developing cardiovascular treatments that range from monoclonal antibodies to immunotherapies to cell therapy.For Cardior, the deal provides a way to reach more patients, Ulbrich said.Our first trial was in post-myocardial heart failure, and this is a niche gap where there arent any causal treatments where patients would clearly fit our treatment, Ulbrich said. But now, we will pursue development in a chronic situation, which is a large patient population.Cardior expects results from a Phase 2 trial by the end of the year or the beginning of 2025, Ulbrich said.While the success of mRNA vaccines for COVID-19 didnt directly influence Cardior, Ulbrich said companies like Germanys BioNTech improved the industrys understanding of RNA technology, particularly among large pharmaceutical companies.Although not all the details of the transaction are set in stone, Cardior will stay as is for the moment, Ulbrich said.I want to oversee the transition and the next development steps because, having worked seven years for this company and for this program, it affects me personally, Ulbrich said. Overall, this looks like the right partnership and the right deal at the right point in time. '

DUBLIN, March 26, 2024 /PRNewswire/ -- Endo International plc (OTC: ENDPQ) announced today that one of its operating companies, Par Pharmaceutical, Inc., launched ibuprofen-famotidine 800 mg/26.6 mg tablets, a generic version of Amgen's (formerly Horizon Therapeutics) DUEXIS®. "We're proud to provide affordable choices to healthcare providers and their appropriate patients while strengthening our reputation as a reliable, quality supplier," said Scott Sims, Senior Vice President and General Manager, Injectable Solutions & Generics at Endo. The combination medication is used to relieve the signs and symptoms of rheumatoid arthritis and osteoarthritis while decreasing the risk of developing ulcers of the stomach and upper intestines people may experience from ibuprofen alone. According to IQVIA™, ibuprofen-famotidine tablet sales were approximately $49 million for the 12 months ended December 31, 2023. DUEXIS® is a registered trademark of Horizon Therapeutics USA, Inc. CONTRAINDICATIONS: Ibuprofen and famotidine tablets are contraindicated in the following patients: Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to ibuprofen or famotidine or any components of the drug product. History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients. In the setting of coronary artery bypass graft (CABG) surgery. Ibuprofen and famotidine tablets should not be administered to patients with a history of hypersensitivity to other H2-receptor antagonists. Cross sensitivity with other H2-receptor antagonists has been observed. WARNINGS AND PRECAUTIONS Cardiovascular Thrombotic Events Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI), and stroke, which can be fatal. To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur. Status Post Coronary Artery Bypass Graft (CABG) Surgery Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG. Post-MI Patients Avoid the use of ibuprofen and famotidine in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If ibuprofen and famotidine is used in patients with a recent MI, monitor patients for signs of cardiac ischemia. Gastrointestinal Bleeding, Ulceration, and Perforation NSAIDs, including ibuprofen, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDS. Strategies to Minimize the GI Risks in NSAID-treated patients: Use the lowest effective dosage for the shortest possible duration. Avoid administration of more than one NSAID at a time. Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding. For such patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs. Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy. If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, and discontinue ibuprofen and famotidine until a serious GI adverse event is ruled out. In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding. Active Bleeding When active and clinically significant bleeding from any source occurs in patients receiving ibuprofen and famotidine, the treatment should be withdrawn. Patients with initial hemoglobin values of 10 g or less who are to receive long-term therapy should have hemoglobin values determined periodically. Hepatotoxicity Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), discontinue ibuprofen and famotidine immediately, and perform a clinical evaluation of the patient. Hypertension NSAIDs, including ibuprofen and famotidine, can lead to new onset of hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs. Monitor blood pressure (BP) during the initiation of NSAID treatment and throughout the course of therapy. Heart Failure and Edema Fluid retention and edema have been observed in some patients treated with NSAIDs. Use of ibuprofen may blunt the CV effects of several therapeutic agents used to treat these medical conditions (e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]). Avoid the use of ibuprofen and famotidine in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If ibuprofen and famotidine is used in patients with severe heart failure, monitor patients for signs and symptoms of worsening heart failure. Renal Toxicity and Hyperkalemia Renal Toxicity Avoid the use of ibuprofen and famotidine in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal failure. If ibuprofen and famotidine is used in patients with advanced renal disease, monitor patients for signs of worsening renal function. Hyperkalemia Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state. Anaphylactic Reactions Ibuprofen has been associated with anaphylactic reactions in patients with and without known hypersensitivity to ibuprofen and in patients with aspirin-sensitive asthma. Seek emergency help if an anaphylactic reaction occurs. Seizures Central nervous system (CNS) adverse effects including seizures, delirium, and coma have been reported with famotidine in patients with moderate (creatinine clearance <50 mL/min) and severe renal insufficiency (creatinine clearance <10 mL/min), and the dosage of the famotidine component in ibuprofen and famotidine is fixed. Therefore, ibuprofen and famotidine is not recommended in patients with creatinine clearance < 50 mL/min. Exacerbation of Asthma Related to Aspirin Sensitivity Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, ibuprofen and famotidine is contraindicated in patients with this form of aspirin sensitivity. When ibuprofen and famotidine is used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma. Serious Skin Reactions NSAIDs, including ibuprofen, which is a component of ibuprofen and famotidine tablets, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions and to discontinue the use of ibuprofen and famotidine at the first appearance of skin rash or any other sign of hypersensitivity. Ibuprofen and famotidine is contraindicated in patients with previous serious skin reactions to NSAIDs. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as ibuprofen and famotidine. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. If such signs or symptoms are present, discontinue ibuprofen and famotidine and evaluate the patient immediately. Fetal Toxicity Limit use of NSAIDs, including ibuprofen and famotidine, between about 20 to 30 weeks in pregnancy due to the risk of oligohydramnios/fetal renal dysfunction. Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy due to the risks of oligohydramnios/fetal renal dysfunction and premature closure of the fetal ductus arteriosus. Masking of Inflammation and Fever The pharmacological activity of ibuprofen and famotidine in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections. Laboratory Monitoring Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a CBC and chemistry profile periodically. Concomitant NSAID Use Ibuprofen and famotidine tablets contain ibuprofen as one of its active ingredients. It should not be used with other ibuprofen-containing products. The concomitant use of NSAIDs, including aspirin, with ibuprofen and famotidine may increase the risk of adverse reactions. Aseptic Meningitis If signs or symptoms of meningitis develop in a patient on ibuprofen and famotidine, the possibility of its being related to ibuprofen should be considered. Ophthalmological Effects Blurred and/or diminished vision, scotomata, and/or changes in color vision have been reported. If a patient develops such complaints while receiving ibuprofen and famotidine, the drug should be discontinued, and the patient should have an ophthalmologic examination which includes central visual fields and color vision testing. ADVERSE EVENTS Most common adverse reactions (>1% and greater than ibuprofen alone) are nausea, diarrhea, constipation, upper abdominal pain, and headache. INDICATION AND USAGE Ibuprofen and famotidine tablets, a combination of the NSAID ibuprofen and the histamine H2-receptor antagonist famotidine, is indicated for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis and to decrease the risk of developing upper gastrointestinal ulcers, which in the clinical trials was defined as a gastric and/or duodenal ulcer, in patients who are taking ibuprofen for those indications. The clinical trials primarily enrolled patients less than 65 years of age without a prior history of gastrointestinal ulcer. Controlled trials do not extend beyond 6 months. Click for Full Prescribing Information, including BOXED WARNING and Medication Guide. About Endo Endo (OTC: ENDPQ) is a specialty pharmaceutical company committed to helping everyone we serve live their best life through the delivery of quality, life-enhancing therapies. Our decades of proven success come from passionate team members around the globe collaborating to bring treatments forward. Together, we boldly transform insights into treatments benefiting those who need them, when they need them. Learn more at or connect with us on LinkedIn. Cautionary Note Regarding Forward-Looking Statements Certain information in this press release may be considered "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 and any applicable Canadian securities legislation including, but not limited to, the statements by Mr. Sims, any statements relating to product launch, quality, affordability, efficacy, reliability or sales, and any statements that refer to expected, estimated or anticipated future results or that do not relate solely to historical facts. Statements including words or phrases such as "believe," "expect," "anticipate," "intend," "estimate," "plan," "will," "may," "look forward," "intend," "guidance," "future," "potential" or similar expressions are forward-looking statements. All forward-looking statements in this communication reflect the Company's current views as of the date of this communication about its plans, intentions, expectations, strategies and prospects, which are based on the information currently available to it and on assumptions it has made. Actual results may differ materially and adversely from current expectations based on a number of factors, including, among other things, the outcome of the Company's contingency planning and restructuring activities; the timing, impact or results of any pending or future litigation, investigations, proceedings or claims, including opioid, tax and antitrust related matters; any actual or contingent liabilities; settlement discussions or negotiations; the Company's liquidity, financial performance, cash position and operations; the risks and uncertainties associated with chapter 11 proceedings; the time, terms and ability to complete a chapter 11 plan of reorganization or to pursuen an alternative emergence transaction; the risk that the Company's chapter 11 cases may be converted to cases under chapter 7 of the Bankruptcy Code; the adequacy of the capital resources of the Company's businesses and the difficulty in forecasting the liquidity requirements of the operations of the Company's businesses; the unpredictability of the Company's financial results; the Company's ability to discharge claims in chapter 11 proceedings; negotiations with the holders of the Company's indebtedness and its trade creditors and other significant creditors; the risks and uncertainties with performing under the terms of the restructuring support agreement and any other arrangement with lenders or creditors while in chapter 11 proceedings; the performance, including the approval, introduction, and consumer and physician acceptance of new products and the continuing acceptance of currently marketed products; and the Company's ability to obtain and successfully manufacture, maintain and distribute a sufficient supply of products to meet market demand in a timely manner. The Company expressly disclaims any intent or obligation to update these forward-looking statements, except as required to do so by law. Additional information concerning risk factors, including those referenced above, can be found in press releases issued by the Company, as well as the Company's public periodic filings with the U.S. Securities and Exchange Commission and with securities regulators in Canada, including the discussion under the heading "Risk Factors" in the Company's most recent Annual Report on Form 10-K and any subsequent Quarterly Reports on Form 10-Q or other filings with the U.S. Securities and Exchange Commission. SOURCE Endo International plc