Cebranopadol hemicitrate

1. 引言 本文基于2025年Q3相关公司在疼痛治疗领域的公开信息，系统梳理了在研及已上市产品的研发进展、作用机制与商业模式。可以看到该领域正经历从传统阿片类药物向非阿片类、高选择性、具有内在防滥用特性的新型疗法的范式转移。主要技术路径集中在靶向特定离子通道（如NaV1.8, NaV1.7）、新型阿片受体（如KOR, DOR, NOP）、以及利用基因治疗、抗体融合蛋白等前沿平台。同时，针对神经病理性疼痛、术后疼痛和慢性疼痛（如纤维肌痛、骨关节炎）等特定适应症的未满足临床需求，成为企业重点布局的方向。 全球范围内，阿片类药物危机和对现有疼痛疗法（如NSAIDs）副作用的不满，共同驱动了对更安全、更有效镇痛方案的迫切需求。本报告旨在分析2025年Q3疼痛治疗领域的创新动态，重点关注临床进展、技术平台和战略布局，以描绘未来的竞争格局与发展方向。 2. 阿片受体靶向药物创新探索，企业正致力于开发靶向非μ-阿片受体的药物，以保留镇痛效果的同时规避成瘾、呼吸抑制等经典副作用。 海思科 (Haisco) - HSK21542 (安瑞克芬注射液) 全球首个获批的高选择性外周κ阿片受体激动剂，用于术后轻中度疼痛。其最大亮点是无需纳入麻精药品管理，解决了阿片类药物流通和使用的核心痛点，具有重大市场价值。PharmNovo - PN6047 首创的δ阿片受体激动剂，避开μ受体，专注于治疗神经病理性疼痛，已获准在欧盟开展IIa期试验。Tris Pharma - Cebranopadol (TRN-228) 同类首创的双NOP/MOP受体激动剂。其III期成功证明，通过协同激活NOP受体，可在实现强效镇痛（与羟考酮相当）的同时，显著降低欣快感和依赖风险。该药物还被开发用于治疗阿片类药物使用障碍，代表了“治痛”与“防瘾”结合的新思路。Ensysce Biosciences - PF614 基于其专有TAAP™和MPAR® 技术平台，旨在提供具有内置滥用防护机制的阿片类药物，目前正推进用于术后疼痛的III期临床试验。 3. 非阿片类靶点的突破与验证，这是当前研发最活跃的领域，主要集中在离子通道和神经信号通路的精准调控。     NaV家族抑制剂（疼痛信号传导的核心）Vertex Pharmaceuticals - Suzetrigine (JOURNAVX™) 首个获批的非阿片类口服NaV1.8抑制剂，用于中重度急性疼痛，标志着疼痛治疗新类别的诞生，具有里程碑意义。Latigo Biotherapeutics - LTG-001 口服NaV1.8抑制剂，因其快速吸收特性（Tmax ~1.5小时）获FDA快速通道资格用于急性疼痛，并成功完成1.5亿美元B轮融资，显示资本市场对其前景的认可。礼来 (Eli Lilly) 收购 SiteOne Therapeutics 核心资产为即将进入II期的NaV1.8抑制剂STC-004，此次收购（价值高达10亿美元）体现了大药厂对NaV1.8靶点在慢性疼痛领域潜力的肯定，旨在巩固其在该赛道的领导地位。Dogwood Therapeutics - Halneuron® (河豚毒素) 靶向NaV1.7通道，开发用于化疗诱导的周围神经病理性疼痛。其差异化在于采用了一种天然神经毒素的高纯度制剂，临床前数据显示其效果与VX-548相当或更优。 其他新兴靶点与机制    AlzeCure Pharma - ACD440 首个进入临床的TRPV1拮抗剂外用凝胶，在II期试验中能将热痛降低约50%，并获FDA孤儿药资格用于红斑性肢痛症，展示了局部精准镇痛的价值。AlzeCure Pharma - ACD137 TrkA负变构调节剂，临床前镇痛效果与抗NGF抗体Tanezumab相当，但可能具有更好的安全性，是骨关节炎疼痛领域的潜力候选药物。Lexicon Pharmaceuticals - Pilavapadin (LX9211) 高选择性AAK1抑制剂，通过非阿片机制调节疼痛信号。其IIb期研究已确定10mg为最优III期剂量，展示了清晰的剂量反应关系。BIODOL Therapeutics - BDT272 FLT3受体的负变构调节剂，独特之处在于既可作非阿片类单药，也可作为阿片类辅助疗法，以增强吗啡疗效并预防耐受和痛觉过敏。 4. 新型给药系统与剂型创新，旨在提高患者依从性、实现长效镇痛或减少系统性副作用。 恒瑞医药 - 布比卡因脂质体注射液 (艾恒平®) 采用DepoFoam多囊脂质体技术的超长效局麻药，通过神经阻滞实现术后区域镇痛。其在中国和美国的成功获批及适应症扩展，体现了高端复杂制剂的市场竞争力和临床价值。Silo Pharma - SP-26 可溶解的缓释氯胺酮植入剂，通过皮下给药提供持续、亚致幻剂量的氯胺酮，旨在为纤维肌痛等慢性疼痛提供防滥用的阿片替代方案。Cessatech - CT-001 舒芬太尼/氯胺酮鼻喷雾剂。其设计巧妙利用了氯胺酮的阿片节约效应，可减少约50%的阿片用量，并结合无创鼻腔给药，极大地提升了儿童急性疼痛治疗的便捷性和安全性，已向EMA提交上市申请。 5. 前沿技术平台的探索，包括基因治疗、蛋白降解剂、细胞疗法和AI驱动研发。 Adolore BioTherapeutics 开发基于单纯疱疹病毒的Kv7激活型基因疗法，在骨关节炎疼痛模型中实现持续超6个月的镇痛，代表了从“对症”到“对因”的潜在长效治疗方案。Cullgen - CG001419 口服泛TRK蛋白降解剂，利用靶向蛋白降解技术清除疼痛信号通路中的关键蛋白，为急慢性疼痛提供了全新作用机制。PharmaTher Holdings - KetAImine™平台 利用AI和专有数据库，系统性挖掘和优化氯胺酮的新适应症与联合疗法，旨在通过505(b)(2)路径加速上市。Encoded Therapeutics 虽然其核心项目ETX101针对中枢神经系统疾病，但其在研的靶向SCN9A/NaV1.7的基因疗法项目，展示了基因药物治疗遗传性疼痛疾病的长期潜力。 6. 研发挫折与失败案例分析，研发过程并非一帆风顺，失败案例同样具有重要参考价值。 Vertex Pharmaceuticals - VX-993 在治疗急性术后疼痛的II期研究中，所有剂量组均未达到主要终点。这表明，即使在同一靶点家族（NaV1.8）内，不同化合物的开发也充满挑战，成功并非必然。Axsome Therapeutics - AXS-14 其新药申请因一项关键试验的设计问题（主要终点设置在8周且采用灵活剂量）被FDA拒绝受理。这凸显了临床试验设计（如固定剂量与灵活剂量、主要终点的选择）对于最终获批的至关重要性。 7. 已获批产品的市场动态 Tonix Pharmaceuticals - Tonmya™ 15年来首个获批的纤维肌痛新药，其舌下含服剂型避免了肝脏首过效应，减少了致失眠代谢物的生成，为这一难治性疾病提供了重要的新选择。Axsome Therapeutics - SYMBRAVOR® 美洛昔康/利扎曲坦复方制剂，获批用于偏头痛急性治疗。其结合了NSAID和曲坦类的协同作用，在临床试验中显示出快速、持久的疗效，满足了偏头痛多模式治疗的需求。8. 讨论 8.1 核心趋势总结“去阿片化”与精准靶向 行业共识是未来属于非阿片类药物。NaV1.8是目前最受验证和追捧的靶点，而KOR、DOR、NOP等阿片受体亚型以及TRPV1、AAK1等新靶点提供了多样化的探索路径。安全性至上 无论是新型阿片类药物（如cebranopadol, PF614）还是非阿片类药物，研发重点都强调降低滥用风险、减少呼吸抑制等副作用。海思科的HSK21542获得“白处方” status，是这一趋势下的重大胜利。剂型与给药途径创新 长效缓释注射剂（恒瑞）、舌下片（Tonix）、鼻喷雾剂（Cessatech）、外用凝胶（AlzeCure）和植入剂（Silo）等创新剂型，正致力于提升患者体验、改善依从性并实现局部/靶向治疗。资本与战略高度活跃 Latigo、Maxion等公司的大额融资，以及礼来对SiteOne的收购，表明资本市场和大型药企正积极布局下一代疼痛疗法，尤其看好具有全新作用机制的资产。适应症聚焦与差异化 企业更倾向于在明确的未满足需求领域（如神经病理性疼痛、纤维肌痛、术后疼痛、骨关节炎疼痛）寻求突破，而非开发“万能”镇痛药。 8.2 挑战与未来展望靶点验证的复杂性 VX-993的失败提醒我们，新靶点和化合物的临床转化仍存在高风险。监管门槛提高 FDA对临床试验设计和终点的要求日益严格（如AXS-14案例），要求企业在研发早期就与监管机构保持密切沟通。未来竞争格局 预计未来几年，NaV1.8抑制剂赛道将日趋拥挤。同时，基因治疗、蛋白降解剂等前沿技术能否在疼痛领域取得实质性突破，值得持续关注。拥有独特技术平台（如Ensysce的防滥用技术、Adolore的基因疗法）的公司可能构筑起强大的竞争壁垒。9. 结论 2025年Q3的疼痛治疗研发领域呈现出前所未有的活力与多样性。行业正在彻底摆脱对传统阿片类药物的依赖，通过多种技术路径——从高度选择性的小分子到生物制剂、基因疗法和新型给药系统——致力于为患者提供更安全、有效和便捷的镇痛选择。Vertex的Suzetrigine获批开启了非阿片类疼痛治疗的新时代，而海思科、Tris、Latigo等公司的进展则展示了不同策略的成功。尽管研发道路充满挑战，但该领域的持续创新无疑将为全球数以亿计的疼痛患者带来新的希望。 文章数据来源：公开信息及各公司官网 关于Target Tracker小程序： 还在为追踪药物靶点研究进展而烦恼？试试 Target Tracker 小程序！用户只需简单几步设定关注的药物靶点，就能一键获取最新的基础研究论文列表，前沿动态一手掌握，研究进展轻松追踪，为科研之路精准导航 ，开启高效科研新体验。 可以通过Target Tracker小程序高效完成以下功能： 热点追踪：添加热点，获得及时的论文更新 便捷搜索：定制搜索，提高论文搜索的精度 Ai助力：快速了解一篇论文的核心内容 “点击进入小程序”

MONMOUTH JUNCTION, N.J.--(BUSINESS WIRE)--Tris Pharma, Inc. (Tris), a commercial-stage biopharmaceutical company, today announced the acceptance of its company-sponsored, peer-reviewed article “The burden of acute pain in the U.S. in the wake of the opioid crisis” for publication in Frontiers in Pain Research. The paper presents critical statistics around the dilemma faced by healthcare professionals and their patients with the prescription of pain medications. Today, acute pain can often only be effectively managed by opioids, and failing to adequately manage severe acute pain substantially increases the risk of that pain becoming chronic. However, the need to utilize opioids must be balanced by their substantial risks of misuse, diversion, dependence and overdose, leaving many with untreated pain or risking it progressing and diminishing their quality of life. The need for safer, highly effective alternatives to today’s pain therapies has never been more urgent. Key highlights from the publication include: ~25% of patients who receive short-term opioid prescriptions experience euphoria 12% (8.3 million) of adult patients who are prescribed opioids end up misusing them; this risk increases among adolescents and teenagers Greater than 50% of patients addicted to heroin, fentanyl and other opioids started as pain patients who felt high (i.e., experienced euphoria) upon taking an opioid medication prescribed to them and went on to misuse the medication Roughly 80% of heroin and fentanyl users first misused prescription opioids before seeking out a greater high There are approximately 80,000 opioid-related overdose deaths per year and hundreds of thousands of non-fatal opioid overdoses, which often lead to significant utilization of healthcare resources and long-term medical complications The total attributable cost of acute and chronic pain in the U.S. was $923 billion in 2024 “Physicians today face significant challenges when treating acute pain. Despite the availability of non-opioid options, opioids are often necessary for effective acute pain relief,” said Charles Argoff, M.D., Albany Medical College and an author of the paper. “Opioids carry inherent risks that are associated with prescribing precautions; however, completely avoiding them in the setting of severe acute pain may result in suboptimal pain reduction, increasing the likelihood of the acute pain becoming chronic. This important publication highlights the urgent need for better therapeutics so that neither physicians nor patients have to choose between effective pain relief and risks detrimental to their quality of life, including addiction.” Details of the Publication Title: The burden of acute pain in the U.S. in the wake of the opioid crisis Authors: James C. Hackworth, Ph.D., Tris Pharma; Charles Argoff, M.D., Albany Medical College; John E. Schneider, Ph.D., Avalon Health Economics; Maggie Do Valle, MPH, Avalon Health Economics; David Fam, Pharm.D., Tris Pharma; Ema Offidani, Ph.D., Tris Pharma; Jim Potenziano, Ph.D., Tris Pharma Tris Pharma commissioned this research in support of its work developing cebranopadol, a dual nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor (dual-NMR) agonist. About Acute Pain Acute pain affects millions of patients each year and is caused by injury, surgery, illness, trauma, burns or painful medical procedures, which can last up to three months, and typically resolves once the underlying cause is treated or healed. Moderate-to-severe acute pain can often only be effectively treated with opioid analgesics such as oxycodone, especially following joint replacements and other orthopedic procedures, invasive surgeries, and major traumas and burns. About Tris Pharma Tris Pharma is a privately held, innovation-driven biopharmaceutical company that is applying its drug development capabilities and proprietary technologies to transform the treatment of ADHD, pain, addiction and disorders of the central nervous system. Tris is an established commercial organization with a robust portfolio of best-in-class ADHD products and a promising pipeline of differentiated, near-term drug candidates such as cebranopadol. More information is available at www.trispharma.com and on LinkedIn @TrisPharma. About Cebranopadol Cebranopadol is a first-in-class investigational therapy that targets two key receptors, the nociceptin/orphanin FQ peptide (NOP) and µ-opioid peptide (MOP) receptors (a dual-NMR agonist), for the treatment of moderate-to-severe pain, as well as opioid use disorder (OUD). These receptors are partially homologous to each other, and they play both complementary and distinct roles to modulate pain biology pathways. Studied in over 33 clinical trials in more than 2,200 patients, cebranopadol’s profile has been well characterized in pain management studies. It has demonstrated positive clinical results in acute pain, chronic pain and diabetic neuropathic pain with a favorable safety profile. The FDA granted Fast Track Designation to cebranopadol for chronic low back pain, and if approved, it could become the first dual-NMR pain-relief therapy with the demonstrated ability to provide efficacy equivalent to opioids with less potential for misuse or risk of physical dependence, addiction or overdose. Cebranopadol’s novel mechanism of action has potential in treating patients with substance use disorders (SUDs). Tris plans to continue to evaluate cebranopadol’s potential to help patients break the cycle of opioid addiction. The National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH), has awarded Tris a five-year grant of up to $16.6 million to study cebranopadol’s potential to treat OUDs and SUDs.