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When a patient is struggling with gastrointestinal (GI) health issues, such as rectal bleeding, inflammatory bowel disease (IBD), or the possibility of colorectal cancer, they must immediately seek medical care. Receiving a timely colonoscopy or endoscopy is essential to developing an individually tailored treatment plan to help the patient recover. Although such services are critical for diagnosing and monitoring disease progression, many Americans face delays and denials due to insurance company practices that disrupt patients’ access to the medically necessary care needed for GI conditions like IBD. One particularly onerous mandate and detrimental insurance barrier is prior authorization, which allows insurers to overrule a physician’s clinical decisions by delaying—or often denying—patients’ access to the health services prescribed by their trusted GI doctor. Prior authorization has become a systemic tool that insurers use to control costs. A recent report from the American Hospital Association found that nearly two-thirds of patients experienced insurance coverage-related barriers like prior authorization within the last two years. Moreover, according to a 2022 American Medical Association survey, four out of five doctors say that prior authorization leads patients to abandon their recommended course of treatment at least some of the time, which can lead to significant adverse health impacts. In fact, 25% of doctors say delays caused by prior authorization have led to a patient’s hospitalization. Insurers must stop prioritizing profits over patient health. Insurers frequently require prior authorization before approving prescriptions to treat patients with IBD and GI conditions, in particular. Physicians are often required to switch a stable IBD patient to a new medication because the insurer negotiated a better price, even if the physician disagrees that the new medication will be as effective. The process for appealing delays and denials can be lengthy, confusing, and cumbersome, requiring physicians to hire multiple full-time staff dedicated to managing the prior authorization process. Ultimately, many patients give up. When required for routine services like colonoscopies and FDA-approved drugs for patients with serious chronic conditions, like IBD, prior authorization goes directly against the standard of care. When I treat patients with IBD, the FDA-approved drugs that are indicated for treatment often require a prior authorization review, yet if I prescribe the steroid prednisone—a medication that is not the standard of care for IBD because it is not effective—most insurers don’t require a prior authorization review at all. They allow the lower cost prednisone without batting an eye. This is unethical and it’s common. According to a study published this month in the American Journal of Gastroenterology, insurers almost always denied coverage of biologic drugs as a first line of treatment, instead requiring patients to fail steroids and immunomodulators first. This runs counter to clinical guidelines. In fact, adherence to American College of Gastroenterology/American Gastroenterological Association guidelines ranged from 5.8% to 58.8% among the nation’s 50 largest insurers and less than 17.65% of policies permitted biologic therapies for IBD patients without first failing other, less expensive, medications. The impact of prior authorization can be devastating. Consider the case of GI patient and law student Chris McNaughton, who was denied treatment by his insurer, UnitedHealthcare (UHC), for his debilitating ulcerative colitis that left him with fatigue, anemia, arthritis, and life-threatening blood clots. His insurer’s egregious use of prior authorization eventually ended in a lawsuit, and a 2023 ProPublica investigation revealed employees at UHC mocking Mr. McNaughton, misrepresenting critical findings, ignoring warnings from his doctors about changing his treatment plan, and being more concerned about the money Mr. McNaughton was costing them rather than his health and wellness. These types of cases, extreme as they are, happen every day. I fear they will become more common if insurers like UHC succeed in implementing prior authorization policies for critical GI services, including diagnostic and surveillance colonoscopies and endoscopies. Any delay in care due to insurance coverage is dangerous. For obvious reasons, insurers would never hold up treatment for pneumonia or hemorrhaging, so why do they do it when patients with IBD have severe flare-ups, which can be just as serious? It doesn’t make sense. To help promote accountability, transparency, and ethical policy development, the American Gastroenterological Association (AGA) recently published a white paper outlining a comprehensive plan for improving IBD care and fixing the insurance barriers plaguing our healthcare system. It recommends that independent review boards be established to ensure insurance coverage policies are evidence-based, patient-centered, and based on clinical best practices. These boards should include patients and medical specialists (for example, gastroenterology experts in IBD) to help regulators and health plans review any policies that may have bias, lack evidence, or don’t adhere to standards of care. Moreover, independent review organizations should be required to review appeals if a patient’s prescribed care is denied, and the prior authorization process should be streamlined. In cases where prior authorization requests are denied and appealed, there should be standard of care reviews done by a “like” physician (e.g., a gastroenterologist with experience in IBD) instead of someone like a pediatrician or dermatologist, as is all too common now. Finally, health plans should publicly report data on rates of initial denials, appeal denials, and response times for accountability. As a gastroenterologist who has witnessed first-hand how prior authorization prevents my patients from receiving necessary treatments and screening for GI conditions and IBD, I’m confident that my patients would benefit from more ethical insurance policies and a national appeals process. Insurers should immediately end their overreach into medical decision-making and work with medical providers and their patients to ensure timely care for all. It’s time for payers to listen to the voices of the medical community and help us expand, not threaten, vital access to care. By ensuring comprehensive coverage for essential monitoring and medications and upholding patient-centered care principles, our leaders can make IBD and GI care accessible, equitable, and effective for all patients.

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。ADC药物已成为时下最热门的赛道之一，吸引了众多药企入局。ADC赛道投融资也呈现出欣欣向荣的发展态势，仅在2024年1-3月间，国内外已有13家ADC药企迎来了新一轮融资进展，融资轮次多处于早期，融资总额超80亿元。Tubulis3月14日，Tubulis宣布成功完成了1.388亿美元的B2轮融资。该轮融资由EQT Life Sciences和Nextech Invest共同领投，新投资者Frazier Life Sciences和Deep Track Capital也参与了投资。Tubulis正在开发下一代抗体偶联药物（ADCs），通过针对特定靶标定制靶向分子和有效载荷的组合，以开发具有优越性能的新型ADCs。B2轮融资获得的资金将主要用于支持Tubulis下一代ADC的临床研发，并帮助实现主打候选药物TUB-040和TUB-030的临床概念验证。TUB-040针对肿瘤抗原Napi2b，这是一个在卵巢癌和肺癌中被详细表征的靶标。而TUB-030针对5T4，这是一个在实体瘤中经常过度表达的抗原。这两款候选药物的临床前概念验证数据将在今年四月的美国癌症研究协会（AACR）年会上汇报。研发管线吉利德2月29日，Carlyle旗下的生命科学投资集团Abingworth宣布已与吉利德（Gilead Sciences）达成融资协议。该融资协议将提供高达2.1亿美元的资金，用于支持其ADC药物Trodelvy（戈沙妥珠单抗，sacituzumab govitecan-hziy）在非小细胞肺癌（NSCLC）的部分临床研究。作为协议的一部分，由Abingworth及其母公司Carlyle投资的临床开发公司Launch Therapeutics 与吉利德签署了一项临床合作协议，将由一组联合指导委员会监督Trodelvy的发展。吉利德将保留Trodelvy的全部权利。如果Trodelvy成功攻克NSCLC，并获得监管部门对标签扩展的批准，Abingworth将获得吉利德公司的固定付款，还有权获得该适应症领域的销售分润。先声药业2月25日，先声药业发布公告称，其子公司先声再明获得9.7亿元融资。本轮融资由先进制造领投，中深新创、杏泽兴涌、鼎信中和跟投，融资资金将用于先声再明主要业务范围内的产品研发、生产及营运。先声药业（2096.HK）是一家创新与研发驱动的制药公司，建设有“神经与肿瘤药物研发全国重点实验室”。公司重点聚焦肿瘤、神经系统、自身免疫及抗感染领域，药物形式上，先声再明布局蛋白工程、T cell engager、NK cell engager、AI辅助分子设计、蛋白降解剂、ADC等，同时积极前瞻性布局未来有重大临床需求的疾病领域，拥有近60个创新药研发管线。研发管线普方生物2024年2月13日，ProfoundBio（普方生物），一家专注于开发治疗实体瘤ADC药物的生物技术公司，宣布完成1.12亿美元（超8亿元）超额认购的B轮融资，以推进其差异化临床阶段ADC管线开发。本轮融资由Ally Bridge Group领投，同时也得到了包括Nextech Invest、T. Rowe Price、Janus Henderson Investors、RA Capital Management和OrbiMed等顶级专业医疗和共同基金机构投资者的支持。本轮融资将推进普方生物在临床前和临床阶段一系列ADC管线的开发，主要针对治疗实体瘤的管线包括：（1）以叶酸受体α（FRα）为靶点的ADC药物Rina-S，目前推进至针对于卵巢癌和子宫内膜癌患者的临床二期研究，预计于今年晚些时候开展卵巢癌的关键临床研究（2）以CD70为靶点的ADC药物PRO1160，目前推进至临床一期研究，初期研究结果预计于2024年发表（3）以蛋白酪氨酸激酶7（PTK7）为靶点的ADC药物PRO1107，目前推进至临床一期研究，初期研究结果预计于2025年发表（4）双抗ADC药物PRO1286，预计于2024年推进至临床阶段。信诺维1月20日，苏州信诺维医药科技股份有限公司（以下简称“信诺维”或“公司”）成功完成了7亿元的E轮系列融资。本轮融资由某一线基金和国鑫投资联合领投，济南产发、华控投资、粤开资本、辰海资本、浦东创投、卓璞资本等多家知名机构共同参与，老股东正心谷资本持续支持，行远致同担任本轮融资的独家财务顾问。本轮募集资金将主要用于推进公司多条管线的国内外临床试验，完善自主创新的靶向治疗、抗感染和PROTAC三大技术平台，加速生产基地运营以及商业化团队建设，推动产品早日上市惠及广大患者。信诺维成立于2017年，是一家兼具科研实力和商业化能力的平台型创新药公司，始终以造福人类健康为己任，致力于为全球范围内重大未满足临床需求提供高质量解决方案。基于自主创新的技术平台，信诺维已形成BLI抑制剂、EZH2抑制剂、hURAT1抑制剂以及新一代ADC等全球领先的创新药管线，覆盖肿瘤、多重耐药菌感染和代谢等疾病领域。目前公司已有9个产品处于国内外临床研发阶段，其中两款产品已进入临床III期。昂阔医药2024年1月4日， 昂阔医药（OnCusp），一家致力于将尖端肿瘤前沿药物转化为创新疗法并造福全球癌症患者的生物制药公司，宣布完成了超额认购的1亿美元（超7亿人民币） A轮融资。本次融资由美国Novo Holdings、OrbiMed 和F-Prime Capital领投，Sofinnova Investments、Catalio Capital Management、Marshall Wace、Forge Life Science Partners、Blackbird BioVentures、CJNV BioVentures和博远资本等跟投，其中博远资本是种子轮的联合领投方之一。自2021年4月成立以来，昂阔医药已募集了1.39亿美元（约10亿人民币）。此次融资所得款项将用于推进公司CUSP06项目，一款靶向CDH6的抗体偶联药物（ADC）的临床开发。此外，还将用于公司产品管线和团队的建设。诺灵生物1月8日，诺灵生物医药科技（北京）有限公司宣布于2023年12月完成数千万元人民币的B1轮融资与新型Her2-ADC产品NC18在中美两国IND申报两大里程碑。 本轮融资由泰珑投资旗下泰鲲基金领投，部分老股东跟投。本轮融资资金将重点支持NC18临床开发和管线中其他ADC品种加速向IND迈进。 NC18为一款靶向her2靶点的新型ADC：采用了全新linker和payload，该组合展现出良好的活性、可控的旁杀效应、更好的抗耐药性。NC18具有更好的PK和递送效率，在细胞株、CDX、PDX等非临床药效模型评价中，其药效、抗耐药、Her2低表达活性等方面均展现了同类最佳表现的潜力。总结目前，全球已有15款ADC药物获批上市,全球ADC临床开发项目500余个，主要集中在肿瘤领域。国内布局ADC的药企主要有两类：一类是通过并购、自研或License in等模式布局ADC管线的传统药企，例如恒瑞医药、华东医药等；另一类是拥有自研类ADC技术平台的Biotech，例如荣昌生物等。2023年有约12家中国公司研发的15款ADC实现海外授权，其中多项授权交易的总金额超10亿美元，总额近250亿美元。参考资料：各公司公告 活动推荐【4.12日上海】Focus抗体/XDC类系列见面会:生物偶联药物，早期研发专场-上海首站蓄势待发，精准聚焦ADC/XDC早期研发最新进展与难点案例，面对面学习头部领先经验，了解行业新兴项目最新数据与趋势，与行业专家共同探索更多市场空间，创造更多产业商机与价值！现场特设新兴项目路演及点评交流，更有大咖点评互动。席位有限，机不可失~

子宫腺肌症是一种慢性激素依赖性疾病，表现为子宫内膜异位生长于子宫肌层中，伴随着周围子宫平滑肌细胞的增生和肥大，导致子宫体积增大。这种状况影响大约20-35%的育龄期女性，主要临床症状包括继发性痛经、月经不规则、子宫增大和生育能力下降。子宫腺肌症的发病机制尚未明确，“内陷”与“化生”两种理论的争议持续存在。目前，由于缺乏有效的药物治疗，许多患者最终选择通过手术切除子宫来治疗，这严重影响了女性的身心健康。因此，深入探究子宫腺肌症的发病机制显得尤为重要。2024年3月15日，嘉兴大学附属妇儿医院的车璇教授团队与同济大学高绍荣教授团队在Protein & Cell在线发表研究论文“Comprehensive transcriptional atlas of human adenomyosis deciphered by the integration of single-cell RNA-sequencing and spatial transcriptomics”。该研究通过结合单细胞RNA测序和空间转录组学技术，全面揭示了子宫腺肌病的分子和空间特征，尤其是首次聚焦于子宫内膜肌层交界区。研究详细描述了异位内膜与在位子宫内膜之间的转录异质性，发现了病灶特异的上皮干细胞（LGR5+）亚群和侵袭性基质细胞亚群，以及子宫腺肌症的微环境特征。这项研究首次提出，子宫腺肌症的起源可能是“内陷”和“化生”理论的共同作用结果，这对于推进诊断和制定有针对性的治疗策略具有重要意义。研究团队收集了4名子宫切除患者（包括3名子宫腺肌病患者和1名子宫肌瘤患者）的15个子宫不同区域的组织样本。通过单细胞RNA测序和空间转录组分析，鉴定了15种细胞类型，揭示了子宫腺肌病子宫不同区域的细胞异质性，特别是子宫内膜肌层交界区的细胞亚群。研究发现，LGR5+细胞在子宫腺肌病病灶中的上皮细胞中显著富集，LGR5是已知的成体干细胞标记物，其在LGR5/WNT信号通路中的作用对于维持组织的正常生理功能至关重要。这一发现提示，LGR5+干/祖细胞上皮细胞可能是子宫腺肌症异位病变的关键参与者，而LGR5/WNT信号通路的激活可能是疾病进展的一个重要驱动因素。此外，研究还揭示了子宫腺肌症病灶中特定的PKIB+间质细胞亚群。这些细胞中PKIB基因的特异性高表达与细胞增殖和侵袭性行为有关，暗示这一亚群在疾病的侵袭性特征中可能起到促进作用。通过单细胞轨迹分析，研究人员进一步发现，WFDC1+间质前体细胞可能是PKIB+间质亚群的前体，在子宫腺肌症的发生和进展中起重要作用。研究还鉴定出7个内皮细胞亚群，观察到内皮细胞的异质性和涉及VEGF和ANGPT通路的异常血管生成信号，表明存在复杂的血管生成环境。最后，作者使用CellPhoneDB和CellChat分析发现病灶中的异位内膜和在位内膜之间的细胞间通信存在明显差异，在病变中涉及PTN、TWEAK和WNT级联的异常信号传导。总体而言，该研究通过单细胞RNA测序和空间转录组技术，绘制了子宫腺肌病子宫不同区域包括子宫内膜肌层交接区的转录图谱，揭示了病灶中独特的细胞亚群、功能异常的信号传导以及复杂的细胞相互作用，为制定精确的诊断和治疗策略提供了重要依据。陈涛、徐怡亮、徐小翠和王建章为论文共同第一作者。嘉兴大学附属妇儿医院车璇教授、同济大学高绍荣教授和吴丽副研究员为本文的共同通讯作者。原文链接：https://life.tongji.edu.cn/14/4f/c12615a332879/page.htm本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！