Meloxicam

前言疼痛的定义是一种实际或与潜在组织相关的、不愉快的感觉和情绪体验，疼痛是五大生命体征之一。但是疼痛尚无统一的划分标准，可根据持续时间与性质、病理学特征、程度、部位等进行疼痛的分类。依据作用机制，现有的镇痛药物主要有阿片类、非甾体抗炎药（NSAIDs）、局部麻醉剂以及其他（如辣椒碱等）四大类。阿片类药物是中重度疼痛的主流药物，通过与大脑和脊髓中的阿片受体结合，减少疼痛信号的传递和感知。非甾体类抗炎药，其镇痛机制主要是抑制炎症过程中产生的环氧合酶（COX）的作用来抑制疼痛，主要应用于炎症疼痛，如关节炎。局麻药可阻止神经冲动传导，多用于急性疼痛。但是，阿片作为最有效的镇痛药物，在镇痛领域最常用的药物，其存在成瘾性以及严重的副作用（便秘、呕吐等）。在美国，阿片的滥用造成的死亡一直居高不下，已成为严重的社会问题。因此寻求开发新型非阿片镇痛药物，成为该领域最迫切的临床需求。但是因为疼痛的机制不明确，给开发新药带来挑战，可以说镇痛领域是最缺乏新分子实体的细分治疗领域之一，另外镇痛药物的长效也是临床的重要需求，所以基于现有的API，利用制剂技术平台开发长效的非阿片类镇痛改良型药物是研发的方向之一。FDA至今已按505b（2）路径批准多款非阿片类长效改良型新药，显示该方向正逐渐被药企关注。Exparel（布比卡因脂质体）2011年10月28日，FDA批准Exparel，用于术后镇痛，2018年4月6日批准新增适应症，用于成人手术后局部镇痛；以及臂丛神经阻滞术镇痛。2021年3月22日批准新增适应症用于6岁及以上患者的术后镇痛，以及成人患者臂丛神经阻滞术镇痛。2023年11月28日新增适应症，用于成人腘窝坐骨神经阻滞术镇痛，以及成人内收肌管阻滞术镇痛。Exparel为Pacira开发的布比卡因脂质体，采用公司专有的多囊脂质体（pMVL）技术平台。pMVL载体基质由微小的球形脂基微粒组成，微粒由许多非同心的蜂窝状内部腔室组成，每个腔室都由脂质膜与相邻腔室隔开。恒瑞医药的布比卡因脂质体注射液于2022年11月获得NMPA批准，恒瑞医药以3类申报上市，仿制的即是Exparel。恒瑞医药的布比卡因脂质体注射液据报道是全球首仿，而且NMPA/CDE豁免了验证性临床，基于BE试验获得批准。多囊脂质体的生产工艺复杂，辅料等严重依赖进口，工艺较难实现线性放大，导致其无法被轻易仿制。Posimir（布比卡因凝胶溶液）2021年2月1日，FDA批准Posimir，用于成人关节镜肩峰下减压术后镇痛，可达72小时长效镇痛。Posimir为布比卡因凝胶溶液，由Durect利用SABER®平台技术开发，SABER®技术核心在于含有乙酸异丁酸蔗糖酯，乙酸异丁酸蔗糖酯是一种酯化糖衍生物，为可生物降解的和具有疏水性的粘性液体。注射前Posimir为流动的液体，注射后乙酸异丁酸蔗糖酯与布比卡因结合，形成凝胶，可持续释放布比卡因72小时。Xaracoll（布比卡因植入体）2020年8月28日，FDA批准Xaracoll，用于成人开放式腹股沟疝气修补术后镇痛，可达24小时镇痛效果。Xaracoll为布比卡因植入体，在手术过程中放入手术部位，可以达到术后镇痛的效果。该品种由Innocoll公司开发，利用公司专有的COLLARx技术平台，大致工艺流程：将I型胶原蛋白（来源于牛、马、羊或猪等动物肌腱）溶解、分散，然后与布比卡因混合、罐装、冷冻干燥、密封包装、灭菌等，最终成品为5cm✖5cm✖0.5cm的多孔纯胶原蛋白基质，能够控制药物释放动态。Zynrelef（布比卡因和美洛昔康的固定剂量复方）2021年5月12日，FDA批准Zynrelef，用于拇囊炎切除术、开放式腹股沟疝气修补术以及全膝关节置换术后镇痛，可产生长达72小时的长效镇痛。Zynrelef为布比卡因和美洛昔康的固定剂量复方，由Heron therapeutics开发，利用专利技术平台Biochronomer，该技术的核心是聚原酸酯，作为API的储库以及缓释材料，可控制药物成分的释放。Qutenza（8%浓度的辣椒素透皮贴剂）2009年11月16日，FDA批准Qutenza，用于带状疱疹神经痛。2020年7月17日批准新增适应症糖尿病性周围神经痛。Qutenza活性成分为8%浓度（179mg）的辣椒素透皮贴剂。（这里强调一点，该品种FDA以1类批准，辣椒素并不是新分子实体，在其他国家已上市多年，但是并没有获得过FDA的批准，FDA对于此种情况均按照1类审批。）辣椒素，是瞬态受体电位香草酸1受体（TRPV1）的高度选择性激动剂。辣椒素的最初作用是激活表达TRPV1的皮肤伤害感受器，由于释放血管活性神经肽而导致刺激性和红斑。皮肤贴剂应用于最疼痛的皮肤区域（最多使用4个贴剂）。疼痛区域由医生专业人员确定，并在皮肤上标记。必须将Qutenza应用于完整无刺激的干性皮肤，并使其足部停留30分钟（糖尿病性周围神经痛）和其他位置60分钟（例如疱疹后神经痛），然后去除贴剂并使用凝胶清洁疼痛区域，一次治疗可确保90天的镇痛效果。总结镇痛领域开发新分子药物较为困难，随着技术和辅料的不断发展，创新制剂的研发开始逐渐兴起，基于制剂技术平台开发改良型药物，成为镇痛领域的研发思路，该领域可以说是制剂技术平台大展身手的领域，亦属于高端制剂的范畴，可以解决镇痛药物在临床使用中的一些问题。封面图来源：pixabay版权声明/免责声明本文为授权转载文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢!药时代官方网站:www.drugtimes.cn联系方式:电话:13651980212微信:27674131邮箱:contact@drugtimes.cn点击这里，观看精彩直播！

2023 oncology care franchise revenue was $107.9 million, exceeding full-year 2023 guidance ZYNRELEF® achieved quarterly record of $5.6 million in Q4 Net Product Sales Ended 2023 with cash and cash equivalents of $80.4 million Announced partnership with CrossLink Life Sciences, LLC to expand ZYNRELEF promotional efforts on January 7, 2024 Received FDA approval for expanded indication of ZYNRELEF on January 23, 2024 SAN DIEGO, March 12, 2024 /PRNewswire/ -- Heron Therapeutics, Inc. (Nasdaq: HRTX) ("Heron" or the "Company"), a commercial-stage biotechnology company, today announced financial results for the three and twelve months ended December 31, 2023 and highlighted recent corporate updates. "In the fourth quarter of 2023, Heron saw continued positive momentum and an increased sales trajectory in both our acute care and oncology care franchises, illustrating how the strategic decisions made over the past year have positioned the Company for long-term success and profitability," said Craig Collard, Chief Executive Officer of Heron. "I am pleased to share this quarterly update and look forward to building upon what we achieved in the fourth quarter of 2023, providing substantial value and meaningful solutions in the acute care and oncology care settings." Business Highlights The ZYNRELEF Vial Access Needle ("VAN") program, to allow for the rapid preparation and administration of ZYNRELEF in the operating room, remains on track for a Prior Approval Supplement ("PAS") submission in Q2 2024 and an anticipated launch in the second half of 2024. The ZYNRELEF Prefilled Syringe ("PFS"), to allow for immediate use of ZYNRELEF, continues to progress with an expected submission for approval in 2026. Gross Margin improved to 71% for the quarter, up from 58% in the same period last year. ZYNRELEF generated record quarterly revenues of approximately $5.6 million. The CrossLink Life Sciences, LLC partnership finalized on January 7, 2024, will ultimately provide up to 650 additional sales representatives promoting ZYNRELEF to orthopedic surgeons. Received FDA approval of our supplemental New Drug Application ("sNDA") for ZYNRELEF which expands the ZYNRELEF label to approximately 13 million procedures annually. Financial Guidance for 2024 The Company reaffirms its full-year 2024 guidance for Product Revenues, Net, Adjusted Operating Expenses and Adjusted EBITDA: Acute Care Franchise Acute Care Franchise Net Product Sales: For the three and twelve months ended December 31, 2023, acute care franchise Net Product Sales were $6.1 million and $19.1 million, respectively, which increased from $3.9 million and $10.2 million, respectively, for the same periods in 2022. ZYNRELEF Net Product Sales: Net Product Sales of ZYNRELEF (bupivacaine and meloxicam) extended-release solution for the three and twelve months ended December 31, 2023 were $5.6 million and $17.7 million, respectively, which increased from $3.9 million and $10.2 million, respectively, for the same periods in 2022. APONVIE® Net Product Sales: Net Product Sales of APONVIE for the three and twelve months ended December 31, 2023 were $0.5 million and $1.4 million, respectively, with no sales in the comparable prior year periods. APONVIE became commercially available in the U.S. on March 6, 2023. Oncology Care Franchise Oncology Care Franchise Net Product Sales: For the three and twelve months ended December 31, 2023, oncology care franchise Net Product Sales were $28.1 million and $107.9 million, respectively, which increased from $26.1 million and $97.5 million, respectively, for the same periods in 2022. CINVANTI® Net Product Sales: Net Product Sales of CINVANTI (aprepitant) injectable emulsion for the three and twelve months ended December 31, 2023 were $24.3 million and $94.9 million, respectively, which increased from $23.1 million and $87.3 million, respectively, for the same periods in 2022. SUSTOL® Net Product Sales: Net Product Sales of SUSTOL (granisetron) extended-release injection for the three and twelve months ended December 31, 2023 were $3.8 million and $13.0 million, respectively, which increased from $3.0 million and $10.2 million, respectively, for the same periods in 2022. Conference Call and Webcast Heron will host a conference call and webcast on March 12th, 2024 at 4:30 pm ET. The conference call can be accessed by dialing (646) 307-1963 for domestic callers and (800) 715-9871 for international callers. Please provide the operator with the passcode 6135354 to join the conference call. The conference call will also be available via webcast under the Investor Relations section of Heron's website at . An archive of the teleconference and webcast will also be made available on Heron's website for 60 days following the call. About ZYNRELEF for Postoperative Pain ZYNRELEF is the first and only dual-acting local anesthetic that delivers a fixed-dose combination of the local anesthetic bupivacaine and a low dose of nonsteroidal anti-inflammatory drug meloxicam. ZYNRELEF is the first and only extended-release local anesthetic to demonstrate in Phase 3 studies significantly reduced pain and significantly increased proportion of patients requiring no opioids through the first 72 hours following surgery compared to bupivacaine solution, the current standard-of-care local anesthetic for postoperative pain control. ZYNRELEF was initially approved by the U.S. Food and Drug Administration (the "FDA") in May 2021 for use in adults for soft tissue or periarticular instillation to produce postsurgical analgesia for up to 72 hours after bunionectomy, open inguinal herniorrhaphy and total knee arthroplasty. In December 2021, the FDA approved an expansion of ZYNRELEF's indication to include foot and ankle, small-to-medium open abdominal, and lower extremity total joint arthroplasty surgical procedures. On January 23, 2024, the FDA approved ZYNRELEF for soft tissue and orthopedic surgical procedures including foot and ankle, and other procedures in which direct exposure to articular cartilage is avoided. Safety and efficacy have not been established in highly vascular surgeries, such as intrathoracic, large multilevel spinal, and head and neck procedures. ZYNRELEF was granted a marketing authorization by the European Commission in September 2020 and by the United Kingdom Regulatory Authority in January 2021. In August 2023, we cancelled the ZYNRELEF U.K. marketing authorization and, in October 2023, we cancelled the ZYNRELEF European Union (EU) marketing authorization, as we do not plan to commercially launch ZYNRELEF in the U.K. or the EU. Please see full prescribing information, including Boxed Warning, at . About APONVIE for Postoperative Nausea and Vomiting (PONV) APONVIE is a substance NK1 Receptor Antagonist (RA), indicated for the prevention of PONV in adults. Delivered via a 30-second IV push, APONVIE 32 mg was demonstrated to be bioequivalent to oral aprepitant 40 mg with rapid achievement of therapeutic drug levels. APONVIE is the same formulation as Heron's approved drug product CINVANTI. APONVIE is supplied in a single-dose vial that delivers the full 32 mg dose for PONV. APONVIE was approved by the FDA in September 2022 and became commercially available in the U.S. on March 6, 2023. Please see full prescribing information at . About CINVANTI for Chemotherapy Induced Nausea and Vomiting (CINV) Prevention CINVANTI, in combination with other antiemetic agents, is indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin as a single-dose regimen, delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) as a single-dose regimen, and nausea and vomiting associated with initial and repeat courses of MEC as a 3-day regimen. CINVANTI is an IV formulation of aprepitant, an NK1 RA. CINVANTI is the first IV formulation to directly deliver aprepitant, the active ingredient in EMEND® capsules. Aprepitant (including its prodrug, fosaprepitant) is the only single-agent NK1 RA to significantly reduce nausea and vomiting in both the acute phase (0–24 hours after chemotherapy) and the delayed phase (24–120 hours after chemotherapy). The FDA-approved dosing administration included in the U.S. prescribing information for CINVANTI include 100 mg or 130 mg administered as a 30-minute IV infusion or a 2-minute IV injection. Please see full prescribing information at . About SUSTOL for CINV Prevention SUSTOL is indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens. SUSTOL is an extended-release, injectable 5-hydroxytryptamine type 3 RA that utilizes Heron's Biochronomer® drug delivery technology to maintain therapeutic levels of granisetron for ≥5 days. The SUSTOL global Phase 3 development program was comprised of two, large, guideline-based clinical studies that evaluated SUSTOL's efficacy and safety in more than 2,000 patients with cancer. SUSTOL's efficacy in preventing nausea and vomiting was evaluated in both the acute phase (0–24 hours after chemotherapy) and delayed phase (24–120 hours after chemotherapy). Please see full prescribing information at . About Heron Therapeutics, Inc. Heron Therapeutics, Inc. is a commercial-stage biotechnology company focused on improving the lives of patients by developing and commercializing therapeutic innovations that improve medical care. Our advanced science, patented technologies, and innovative approach to drug discovery and development have allowed us to create and commercialize a portfolio of products that aim to advance the standard-of-care for acute care and oncology patients. For more information, visit . Non-GAAP Financial Measures To supplement our financial results presented on a GAAP basis, we have included information about certain non-GAAP financial measures. We believe the presentation of these non-GAAP financial measures, when viewed with our results under GAAP and the accompanying reconciliations, provide analysts, investors, lenders, and other third parties with insights into how we evaluate normal operational activities, including our ability to generate cash from operations, on a comparable year-over-year basis and manage our budgeting and forecasting. In our quarterly and annual reports, earnings press releases and conference calls, we may discuss the following financial measures that are not calculated in accordance with GAAP, to supplement our consolidated financial statements presented on a GAAP basis. Adjusted EBITDA Adjusted EBITDA is a non-GAAP financial measure that represents GAAP net income or loss adjusted to exclude interest expense, interest income, the benefit from or provision for income taxes, depreciation, amortization, stock-based compensation, and other adjustments to reflect changes that occur in our business but do not represent ongoing operations. Adjusted EBITDA, as used by us, may be calculated differently from, and therefore may not be comparable to, similarly titled measures used by other companies. There are several limitations related to the use of adjusted EBITDA rather than net income or loss, which is the nearest GAAP equivalent, such as: adjusted EBITDA excludes depreciation and amortization, and, although these are non-cash expenses, the assets being depreciated or amortized may have to be replaced in the future, the cash requirements for which are not reflected in adjusted EBITDA; we exclude stock-based compensation expense from adjusted EBITDA although: (i) it has been, and will continue to be for the foreseeable future, a significant recurring expense for our business and an important part of our compensation strategy; and (ii) if we did not pay out a portion of our compensation in the form of stock-based compensation, the cash salary expense included in operating expenses would be higher, which would affect our cash position; adjusted EBITDA does not reflect changes in, or cash requirements for, working capital needs; adjusted EBITDA does not reflect the benefit from or provision for income taxes or the cash requirements to pay taxes; adjusted EBITDA does not reflect historical cash expenditures or future requirements for capital expenditures or contractual commitments; we exclude restructuring expenses from adjusted EBITDA. Restructuring expenses primarily include employee severance and contract termination costs that are not related to acquisitions. The amount and/or frequency of these restructuring expenses are not part of our underlying business; Adjusted Operating Expenses Adjusted operating expenses is a non-GAAP financial measure that represents GAAP operating expenses adjusted to exclude stock-based compensation expense, depreciation and amortization, and other adjustments to reflect changes that occur in our business but do not represent ongoing operations. Reconciliations of adjusted EBITDA and adjusted operating expenses to the most directly comparable GAAP financial measures are included in this press release. The Company has not provided a reconciliation of its full-year 2024 guidance for adjusted EBITDA or adjusted operating expenses to the most directly comparable forward-looking GAAP measures, in reliance on the unreasonable efforts exception provided under Item 10(e)(1)(i)(B) of Regulation S-K, because the Company is unable to predict, without unreasonable efforts, the timing and amount of items that would be included in such a reconciliation, including, but not limited to, stock-based compensation expense, acquisition related expense and litigation settlements. These items are uncertain and depend on various factors that are outside of the Company's control or cannot be reasonably predicted. While the Company is unable to address the probable significance of these items, they could have a material impact on GAAP net income and operating expenses for the guidance period. Forward-looking Statements This news release contains "forward-looking statements" as defined by the Private Securities Litigation Reform Act of 1995. Heron cautions readers that forward-looking statements are based on management's expectations and assumptions as of the date of this news release and are subject to certain risks and uncertainties that could cause actual results to differ materially. Therefore, you should not place undue reliance on forward-looking statements. Examples of forward-looking statements include, among others, statements we make regarding the potential market opportunities for ZYNRELEF, APONVIE, CINVANTI and SUSTOL; revenue, adjusted EBITDA and other financial guidance provided by the Company; the results of the commercial launch of APONVIE; the potential additional market opportunity for the expanded U.S. label for ZYNRELEF; the timing of the Company's development of the VAN program and receipt of required regulatory approvals; our ability to establish and maintain successful commercial arrangements like our co-promotion agreement CrossLink Life Sciences; the outcome of the Company's pending ANDA litigation; whether the Company is required to write-off any additional inventory in the future; the expected future balances of Heron's cash, cash equivalents and short-term investments; the expected duration over which Heron's cash, cash equivalents and short-term investments balances will fund its operations and the risk that future equity financings may be needed; any inability or delay in achieving profitability. Important factors that could cause actual results to differ materially from those in the forward-looking statements are set forth in our most recent Annual Report on Form 10-K and any subsequent Quarterly Reports on Form 10-Q, and in our other reports filed with the Securities and Exchange Commission, including under the caption "Risk Factors." Forward-looking statements reflect our analysis only on their stated date, and Heron takes no obligation to update or revise these statements except as may be required by law. Investor Relations and Media Contact: Ira Duarte Executive Vice President, Chief Financial Officer Heron Therapeutics, Inc. [email protected] 858-251-4400 SOURCE Heron Therapeutics, Inc.