Pretomanid

Central to Viatris’ decision to acquire Pacira BioSciences is the opportunity to develop its portfolio of non-opioid pain management therapies. Credit: Viatris Viatris CEO Scott Smith says the acquisition enables the firm to “strengthen our position in non-opioid pain management” and drive business growth In the latest pharmaceutical industry deal, Viatris has announced plans to acquire Pacira BioSciences , a specialist in innovative non-opioid pain therapies. The deal, thought to be worth around US$1.65bn, adds Pacira’s two patented medicines, acute post-surgical pain therapy Exparel and osteoarthritis knee pain treatment Zilretta, to Viatris’ portfolio. Pacira generated approximately US$746m in total revenue during the last twelve months ended 30 June 2026. Viatris CEO Scott Smith says the acquisition marks a further step in the company’s strategy to strengthen its innovative medicines portfolio and drive sustainable growth. Scott Smith, CEO of Viatris. Credit: Viatris On LinkedIn, following the announcement, Scott writes that the deal “advances the strategy we laid out earlier this year – to drive our base business, fuel our innovative portfolio and modernise for sustainable growth. “Pacira brings established medicines, a promising pipeline and important capabilities that complement our existing portfolio and strengthen our position in non-opioid pain management, an area of significant unmet need. “Just as importantly, this is about where we go from here. We see an opportunity to build on these medicines and capabilities to support the continued growth of our innovative medicines portfolio.” “ Pacira brings established medicines, a promising pipeline and important capabilities that complement our existing portfolio. ” Scott Smith CEO of Viatris Viatris is a global healthcare company formed in 2020 following the merger of Mylan and Pfizer’s Upjohn division. Headquartered in Pittsburgh, Pennsylvania, it aims to expand access to medicines worldwide, offering a portfolio spanning generics, branded medicines and over-the-counter products across therapeutic areas, including cardiovascular disease, oncology and ophthalmology. Reducing opioid overreliance Central to Viatris’ decision to acquire Pacira is the opportunity to strengthen its position in non-opioid pain management, as healthcare providers seek additional options for treating acute and chronic pain. Alongside Pacira’s two marketed therapies Exparel and Zilretta, the company is developing candidates for additional pain management applications, potentially broadening the range of conditions that can be treated with non-opioid approaches. Viatris’ Acquisition of Pacira BioSciences: Key Facts US$1.65bn — Approximate value of Viatris’ planned acquisition of Pacira BioSciences. US$746m — Pacira’s revenue for the 12 months ended 30 June 2026. US$177m — Pacira’s adjusted EBITDA over the same 12-month period. 2 marketed therapies — Exparel for post-surgical pain and Zilretta for osteoarthritis-related knee pain. 20 million patients — Pacira’s reported patient reach through its commercial portfolio, according to CEO Frank Lee. The acquisition comes against the backdrop of the US opioid crisis , which has exposed the risks associated with opioid dependence and the importance of appropriate pain management strategies. Although opioid-involved overdose deaths have declined from recent peaks, they remain a significant public health concern, with the crisis still labelled a public health emergency. The US recorded an estimated 54,743 opioid-involved overdose deaths in 2024, down from 83,140 in 2023, according to data from the Centres for Disease Control and Prevention (CDC). Frank Lee, CEO of Pacira BioSciences. Credit: Pacira BioSciences Frank Lee, CEO of Pacira, says developing non-opioid alternatives for pain management has been central to the company’s mission. On LinkedIn, he writes: “For more than two decades, our mission has been clear: to deliver innovative, non-opioid pain therapies to transform the lives of patients. Together, we have helped reshape the conversation around pain – raising awareness, expanding access and accelerating the adoption of opioid-sparing therapies. “I’m incredibly proud of what our team has built: a leading commercial portfolio that has reached more than 20 million patients, meaningful progress against our 5x30 strategy and an innovative pipeline with the potential to shape the future of patient care.” “ For more than two decades, our mission has been clear: to deliver innovative, non-opioid pain therapies to transform the lives of patients. ” Frank Lee CEO of Pacira BioSciences Expanding product reach Viatris also expects the acquisition to complement its own pipeline of non-opioid pain treatments, including a fast-acting formulation of meloxicam for moderate-to-severe acute pain. The US Food and Drug Administration (FDA) accepted Viatris’ new drug application for the candidate in May 2026, with a regulatory decision expected by the end of December. If approved, the treatment would further strengthen the company’s position in acute pain management, alongside Pacira’s established therapies for post-surgical pain and osteoarthritis-related knee pain. Beyond its existing US market, Viatris plans to use its international infrastructure and intellectual property expertise to extend the reach of Exparel and Zilretta into selected markets, while maximising the long-term value of the acquired portfolio. Financially, the deal is expected to be immediately accretive to Viatris’ financial guidance metrics. The company intends to fund the transaction primarily through excess cash, supplemented by short-term borrowing, which it expects to have a minimal impact on its gross leverage ratio. Subject to customary closing conditions, the acquisition is expected to complete by the end of 2026, marking a further step in Viatris’ strategy to expand its innovative medicines business and establish a stronger position in non-opioid pain management. Viatris – key partners Gilead Sciences CEO : Daniel O’Day | HQ : Foster City, California Viatris and Gilead have collaborated to expand global access to remdesivir, an antiviral developed for COVID-19. Their partnership reflects a shared focus on making treatments available to patients across international markets, particularly during a public health emergency when equitable access to medicines was a major challenge. TB Alliance President & CEO : Dr Mel Spigelman | HQ : New York Viatris has partnered with TB Alliance to increase access to pretomanid, a medicine used in combination regimens to treat certain forms of drug-resistant tuberculosis. The collaboration brings together pharmaceutical manufacturing and development capabilities with a global health organisation focused on developing and delivering more effective, affordable tuberculosis treatments. Bill and Melinda Gates Foundation CEO: Mark Suzman | HQ : Seattle, Washington The Gates Foundation has worked with Viatris to expand access to affordable HIV treatment in low- and lower-middle-income countries. The partnership supports efforts to address barriers to essential medicines in underserved communities, aligning with Viatris’ wider mission to improve global access to quality treatments and strengthen healthcare provision in resource-limited settings. Company portals Pacira BioSciences Viatris Executives Frank Lee Board Member Scott A. Smith Chief Executive Officer

结核病（Tuberculosis, TB）由结核分枝杆菌（*Mycobacterium tuberculosis*）引起，于2023年重新成为全球最致命的单一病原体传染病，当年新增病例1080万例，死亡125万例。耐药结核病的日益严重、卡介苗（BCG）在成人中保护效力欠佳，以及弱势群体持续存在的治疗缺口，共同推动治疗策略向机制驱动、精准导向的方向转变。本综述对2020至2025年间抗结核研究进展进行了批判性整合评估，依据结构生物学、多组学及真实世界临床证据。不同于传统的描述性文献汇编，该综述通过系统性的跨人群疗效比较、对转化瓶颈的深入剖析以及对新兴生物疗法明确的分阶段成熟度划分，突出了其独特价值。研究人员综合了六个相互关联领域的进展：药物靶点的机制洞察与耐药性的时空演化、新型短程治疗方案、精准医学策略、宿主导向疗法、肺外结核的靶向递送系统以及下一代疫苗开发。其中特别强调了三项变革性突破：结构生物学指导的合理药物设计、结核性肉芽肿的空间免疫分析以及人工智能辅助诊断流程。最后，研究人员概述了与WHO终止结核病策略（End TB Strategy）相一致的优先研究方向，为推进全球结核病消除工作提供了转化路线图。这一严谨的多维度综合为推进基础与转化抗结核研究及指导全球公共卫生战略提供了权威参考。抗结核药物靶点与耐药机制 该部分首先深化了经典靶点的机制理解。在能量代谢方面，贝达喹啉（bedaquiline）结合ATP合酶c亚基疏水腔的机制得到阐明，Rv0678突变介导的构象阻断导致MmpS5-MmpL5外排泵过表达，从而产生耐药；其类似物TBAJ-587与人类ATP合酶的交叉反应性也被解析。呼吸链中的细胞色素bcc复合物、细胞色素bd氧化酶等结构被确定，为优化抑制剂提供依据。细胞壁合成方面，德拉马尼（delamanid）的Ddn酶激活动力学、普托马尼（pretomanid）对休眠菌分枝菌酸合成的抑制，以及Rv3806c结构揭示的乙胺丁醇耐药别构机制均被阐明。蛋白质合成方面，恶唑烷酮与50S核糖体结合、核糖体RNA甲基转移酶TlyA修饰、苯丙氨酰tRNA合成酶（PheRS）等结构研究指导新抗生素开发。药物外排泵方面，新发现的异烟肼外排泵MsRv1273c/72c以及MmpL5/MmpS5复合物结构为抑制剂设计提供基础。毒力因子调控如PhoPR系统、KatG等也被列为潜在靶点。新兴靶点方面，表面等离子共振（SPR）技术用于药物-靶点相互作用验证；细胞壁合成新兴靶点包括AftA、DprE2、MabA、KasA、Pks13、MmpL3等；靶向蛋白降解（TPD）技术可靶向“不可成药”蛋白；休眠菌靶点如异柠檬酸裂解酶、RpfB等，以及免疫检查点相关靶点也被提及。耐药机制时空演化方面，文章阐述了经典耐药进展、非编码RNA和表观遗传调控、宿主微环境导致的耐受、交叉耐药网络以及微生物群对耐药的影响。空间生物学技术（如空间转录组学、多重免疫荧光）重塑了肉芽肿免疫图谱，未来方向包括高分辨率时空动态模型、靶向非编码区的药物开发及微环境调节。 耐药结核病的分层治疗方案 BPaL方案将耐多药结核病（MDR-TB）疗程缩短至6–9个月，治愈率约90%，真实世界数据如TB-PRACTECAL研究证实其疗效，但需优化利奈唑胺剂量以平衡毒性。对于准广泛耐药/广泛耐药结核病（pre-XDR/XDR-TB），中国的一项多中心研究评估了三种9个月全口服五药方案的疗效与安全性。未来重点包括大规模真实世界证据验证、苯并咪唑类药物的临床转化、适应性试验设计与精准医学的整合，以建立更分层、个体化和全球适用的诊疗框架。 新型抗结核药物与短程治疗方案 已批准新药方面，BPaL/BPaLM方案疗效好但需监测安全性，吸入型spectinamides替代利奈唑胺等改良方案在探索中；普托马尼单用有耐药风险，但Nix-TB和ZeNix试验显示良好肝安全性。利奈唑胺毒性可通过降低剂量（如300 mg）和缩短疗程来减轻，新一代恶唑烷酮如OTB-658显示出更好安全性。德拉马尼耐药日益受到关注，JDB0131作为新一代硝基咪唑类药物具有更好药代特性和更低毒性。在研新药包括下一代二芳基喹啉TBAJ-876、DprE1抑制剂BTZ043/PBTZ169/TBA-7371/OPC-167832、亮氨酰tRNA合成酶抑制剂GSK3036656（ganfeborole），以及中国自主研发的苏达吡啶（sudapyridine）、TBI-166、康替唑胺（contezolid）、JDB0131等。短程方案突破方面，多项试验证明4个月疗程对药物敏感结核病有效；含氯法齐明、乙硫异烟胺的4个月方案与标准6个月方案比较；中国研究评估9个月全口服方案治疗MDR/pre-XDR-TB；潜伏结核感染（LTBI）短程预防如3HP、4R等。未来应系统整合短程方案和耐药监测。 抗结核药物的不良反应 抗结核药物性肝损伤（AT-DILI）是最常见严重不良反应，异烟肼、利福平和吡嗪酰胺为主要肝毒性药物，NAT2基因多态性与风险相关。神经毒性包括周围神经病变（异烟肼、利奈唑胺）、视神经炎（乙胺丁醇）、精神神经症状（环丝氨酸）。胃肠道反应和皮肤反应常见，其他包括氨基糖苷类的耳肾毒性、QT间期延长等。研究进展包括生物标志物（miR-122、HMGB1、K18）、AI预测模型、PK/PD指导剂量优化、新一代药物及纳米递送减少毒性。药物相互作用方面，贝达喹啉经CYP3A4代谢，与利福平等诱导剂或抑制剂合用需谨慎，与抗逆转录病毒药物存在相互作用。管理路径包括监测阈值、停药标准和再激发策略，特殊人群如HIV共感染、肝病患者需加强监测。 创新干预与递送技术 精准医学策略包括基因型检测（如*pncA*突变、GeneXpert、全基因组测序）、药物基因组学和PK/PD模型指导剂量（如PopPK、PBPK）、特殊人群个体化方案（儿童、糖尿病、吸烟者）以及AI在数字病理和影像诊断中的应用。靶向递送系统方面，脊柱结核采用载药骨水泥/植入物、骨靶向纳米粒；结核性脑膜炎采用跨血脑屏障纳米载体（如转铁蛋白修饰）、鞘内注射；淋巴结结核采用淋巴靶向递送；病变响应型（酶响应、活性氧响应）和黏膜靶向制剂（吸入干粉）也在开发中。 宿主导向治疗与生物疗法 宿主导向治疗（HDT）的临床探索包括靶向炎症小体（如黄芩素抑制NLRP3/AIM2介导的焦亡）、增强自噬（如TRIM27、胺碘酮、熊果酸、小檗碱）、调节髓源性抑制细胞（MDSCs）（全反式维甲酸ATRA）、补充维生素D等。体液免疫方面，研究发现B细胞亚群改变，BCR识别结核分枝杆菌抗原，滤泡辅助性T细胞（Tfh）在生发中心反应中起核心调控作用，靶向Tfh-B细胞轴是潜在HDT策略。细胞治疗方面，CAR-T、TCR-T、细胞因子诱导的杀伤细胞（CIK）、树突状细胞疫苗、间充质干细胞（MSC）疗法正在探索，其中MSC疗法已进入II期临床，但需注意其可能提供耐药和保护性微环境。小核酸药物包括siRNA、circRNA制剂，尚处于临床前概念验证阶段。噬菌体治疗处于临床前和早期同情使用阶段，D29和DS6A等噬菌体有效裂解结核分枝杆菌，与抗生素联用有协同作用。转化挑战包括免疫原性、递送效率、安全性和监管问题。 新型疫苗与潜伏感染干预 治疗性疫苗包括多阶段融合蛋白疫苗（如SHR3、ERA005f）、病毒载体疫苗（ChAdOx1 85A-MVA85A、AdHu5Ag85A）、DNA疫苗（B21）、mRNA疫苗（BNT164）和重组BCG疫苗（VPM1002）。黏膜疫苗通过鼻内接种诱导分泌型IgA（sIgA）和组织驻留记忆T细胞，有望阻断呼吸道感染。预防性干预技术包括基于CD34+造血干细胞潜伏库的检测，短程预防方案（3HP、4R），以及电子药盒、移动健康应用等数字工具提高依从性。 未来展望与结论 过去五年抗结核研究取得标志性进展，但全球防控仍面临耐药菌社区传播、新技术转化不足、特殊人群适应性差等挑战。未来优先方向包括：深入研究休眠菌生物学和非编码RNA/表观遗传耐药机制；加速新药临床试验和纳米递送系统转化；构建多组学与AI融合的精准医学平台；开发新一代黏膜疫苗和扩大LTBI干预；加强跨国耐药监测和能力建设。