Phase 2, Randomized, Open-Label Clinical Trial Evaluating Nogapendekin Alfa Inbakicept in Combination With Standard of Care Versus Standard of Care Alone in Critically Ill Adults With Sepsis and Persistent Lymphopenia

This is a Phase 2, randomized, open-label study evaluating the safety and efficacy of nogapendekin alfa inbakicept (NAI, ANKTIVA®) in combination with standard of care versus standard of care alone in critically ill adults with sepsis and persistent lymphopenia. The study aims to determine whether NAI can improve 28-day mortality by addressing the immunosuppressive phase of sepsis characterized by persistent lymphopenia (absolute lymphocyte count <1,000 cells/µL). Participants will be randomized 1:1 to receive either NAI 1.2 mg subcutaneous injection on Days 3 (or earlier if ALC <700 cells/µL), Day 14, and potentially Day 21 if ALC remains <1,000 cells/µL, plus standard of care, or standard of care alone. The study will enroll approximately 50 participants (25 per arm) with persistent lymphopenia.

开始日期2026-07-06

申办/合作机构

ImmunityBio, Inc.

NCT07488884

/ Not yet recruiting临床1期

Open-Label, Phase 1 Clinical Trial of Neoadjuvant Nogapendekin Alfa Inbakicept, Sotevtamab, and Zabadinostat in Combination With Gemcitabine and Nab-Paclitaxel for Participants With Borderline Resectable or Locally Advanced Pancreatic Cancer

This is an open-label, phase 1 clinical trial to evaluate the safety and preliminary efficacy of neoadjuvant chemoimmunotherapy (NAI, sotevtamab, and zabadinostat in combination with gemcitabine and nab-paclitaxel) followed by resection and adjuvant immunotherapy for participants with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (PDAC). Eligible participants will undergo endoscopic ultrasound (EUS)-guided biopsies of the primary pancreatic tumor within 7 days of enrollment and prior to study day 1. EUS-guided biopsies will be used for histopathological examination to give clinical diagnostic information (as SoC) and will be stored in an ethically approved tissue bank.

开始日期2026-06-01

申办/合作机构

ImmunityBio, Inc.

NCT07524257

/ Not yet recruiting临床3期

Phase 3, Randomized, Open-Label Study of Nogapendekin Alfa Inbakicept in Combination With Standard of Care Versus Standard of Care as First-Line Treatment for Patients With Advanced or Metastatic Non-Small Cell Lung Cancer

This is a randomized, open-label, phase 3 study evaluating nogapendekin alfa inbakicept (NAI) plus chemoimmunotherapy containing pembrolizumab and platinum-based chemotherapy versus chemoimmunotherapy alone as first-line treatment in patients with stage IV squamous or nonsquamous non-small cell lung cancer (NSCLC) without actionable genomic alterations. Primary endpoint is progression-free survival by RECIST v1.1 based on blinded independent central review.

开始日期2026-05-29

申办/合作机构

ImmunityBio, Inc.

100 项与诺格白介素α-因奇西普相关的临床结果

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100 项与诺格白介素α-因奇西普相关的转化医学

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100 项与诺格白介素α-因奇西普相关的专利（医药）

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354

项与诺格白介素α-因奇西普相关的文献（医药）

2026-12-31·JOURNAL OF MEDICAL ECONOMICS

Budget impact model of nadofaragene firadenovec for the treatment of high-risk non-muscle-invasive bladder cancer that is unresponsive to Bacillus Calmette-Guérin immunotherapy

Article

作者: Ye, Dongni ; Yang, Min ; Chai, Xinglei ; Moradi, Ashton ; Zhao, Angela ; Lotan, Yair

AIMS:

To estimate the budget impact of adopting nadofaragene firadenovec for the treatment of adults with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors (CIS ± Ta/T1) from a US third-party payer's perspective.

METHODS:

A budget impact model was developed to compare total healthcare costs under two scenarios: (1) with nadofaragene firadenovec included in the treatment mix, and (2) without it. The model simulated a hypothetical US health plan covering one million members over a 3-year time horizon. Costs assessed included drug acquisition and administration, surveillance and disease management, cystectomy, and treatment-related adverse events (AEs). Base-case inputs were informed by trial data, published literature, and real-world evidence. Scenario analyses explored alternative population definitions, epidemiology and clinical inputs; one-way sensitivity analyses tested parameter uncertainty.

RESULTS:

In the base-case, the estimated per-member-per-month (PMPM) budget impact of adopting nadofaragene firadenovec ranged from $0.0010 in Year 1 to $0.0084 in Year 3. Increased drug and administration costs were partially offset by cost savings from reduced disease progression, fewer cystectomies, and lower AE rates. Scenario analyses demonstrated that even examining a broader population including papillary disease-only patients, the budget impact remained modest ($0.0064-$0.0548 PMPM from Years 1-3). Sensitivity analyses confirmed that results were most influenced by uptake rate, drug cost, and target population size.

LIMITATIONS:

Key limitations include reliance on projected market shares for nadofaragene firadenovec, omission of recently approved treatments (nogapendekin alfa inbakicept-pmln and TAR-200) due to the lack of publicly available market share data, and assumptions to derive clinical outcomes for certain treatments due to lack of reported data.

CONCLUSIONS:

Despite its higher acquisition cost, the inclusion of nadofaragene firadenovec resulted in a minimal budget impact as bladder-sparing option for patients with BCG-unresponsive NMIBC with CIS ± Ta/T1.

2026-06-01·CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY

Advances in intravesical therapy for non-muscle-invasive bladder cancer

Review

作者: Tang, Yanfeng ; Zeng, Hao ; Zhu, Qiyu ; Xu, Chenhao ; Chen, Junru ; Liu, Haoyang ; Wang, Ling

Non-muscle-invasive bladder cancer (NMIBC) accounts for roughly 75% of newly diagnosed bladder cancer and associates with high risk of recurrence and progression. Intravesical therapy remains the cornerstone of NMIBC management following transurethral resection of bladder tumor (TURBT). For low-risk NMIBC, immediate single instillation of chemotherapy after TURBT effectively reduces recurrence. Intermediate-risk patients could benefit from either intravesical chemotherapy or Bacillus Calmette-Guérin (BCG) instillation, with emerging therapies such as UGN-102 chemoablation showing promise. For high/very high-risk NMIBC, full-dose, 3-year BCG instillation remains the standard of care, However, global BCG shortages and treatment failures have prompted the need for alternative strategies. Optimization of BCG regimens, such as two induction courses, may preserve efficacy while improving feasibility. Moreover, alternative agents such as sequential gemcitabine and docetaxel instillation have demonstrated favorable outcomes in both BCG-naïve and BCG-unresponsive patients. For those with BCG failure, a number of novel therapies are under active investigation. Gene therapy (nadofaragene firadenovec), oncolytic viral therapy (CG0070), interleukin-15 superagonist (Nogapendekin alfa-inbakicept), and innovative drug delivery systems (TAR-200) have shown encouraging clinical potential in this population. This review provides an overview of current intravesical treatment strategies for NMIBC across different risk groups and highlights promising new approaches aimed at overcoming the limitations of BCG therapy.

2026-05-01·Biomaterials advances

A novel ROS switcher potentiates the type-I photodynamic effect of sodium zinc chlorophyllin against Pseudomonas aeruginosa in diabetic wounds

Article

作者: Yuan, Cai ; Wang, Guodong ; Chen, Hongjie ; Huang, Mingdong ; Wu, Lusheng

Skin wound infections present a serious threat to human health, with bacterial infections in diabetic wounds being particularly challenging due to impaired healing. Gram-negative bacteria are common pathogens in diabetic wound infections and often exhibit high resistance to conventional treatments, necessitating prolonged and costly therapies. Photodynamic antibacterial therapy (PACT) is regarded as a non-invasive and effective approach, with minimal risk of inducing resistance. Sodium zinc chlorophyllin (ZnChl), a water-soluble metalloporphyrin photosensitizer, offers multiple advantages such as low cost, high safety, and the ability to promote wound healing. However, its bactericidal efficacy against Gram-negative bacteria is limited under the hypoxic conditions typically found in diabetic wounds. Herein, we report a strategy to develop an efficient chlorophyll-based photosensitizer operating via an oxygen-independent Type I mechanism by combining ZnChl with inorganic salts (NaI, KBr, or KI). This approach significantly improved antibacterial performance, particularly with NaI or KI. Upon 630 nm light irradiation, low concentrations of KI (5 mM) markedly enhanced the bactericidal effect of ZnChl (50 μM), reducing the survival of three Gram-negative bacterial strains by 3 logs (99.9%). Interestingly, we further discovered that KI acts as a "reactive oxygen species (ROS) converter," shifting the photodynamic mechanism of ZnChl from a mixed Type I/Type II mode to a dominant Type I mechanism, generating highly reactive hydroxyl radicals (OH). Moreover, the ZnChl-KI combination demonstrated significant therapeutic efficacy in treating Pseudomonas aeruginosa-infected diabetic wounds without inducing apparent toxicity in rats. This work provides a foundation for developing efficient and economical Type I photosensitizers for the treatment of bacterial infections in diabetic wounds.

378

项与诺格白介素α-因奇西普相关的新闻（医药）

2026-05-10

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卢洪洲教授：HIV/AIDS功能性治愈进展及“深圳探索”

编者按：在近日举行的第十一届全国艾滋病学术大会上，深圳市第三人民医院（南方科技大学第二附属医院）院长、国家感染性疾病临床医学研究中心主任卢洪洲教授系统梳理了HIV感染及艾滋病（HIV/AIDS）患者功能性治愈领域的国际前沿进展，并全面展示了其团队在该领域的系统性研究成果与战略布局。从国际最新临床试验到国内自主研发，从基础机制探索到临床转化应用，卢洪洲教授勾勒出了一幅通向艾滋病功能性治愈的清晰路线图。近年来，HIV/AIDS功能性治愈研究在全球范围内呈现出百花齐放的态势。从广谱中和抗体到免疫调节剂，从潜伏病毒库研究到干细胞移植，从新型药物研发到精英控制者机制解析，多条技术路线同步推进，不断刷新着人们对“治愈”可能性的认知。01 当前HIV/AIDS功能性治愈的主流策略卢洪洲教授首先回顾了当前HIV/AIDS功能性治愈的主流策略以及近期全球重要研究进展。单克隆抗体联合治疗靶向于HIV病毒包膜蛋白（如gp120、gp41）或感染细胞表面CD4受体的单克隆抗体（bNABs）是近年来功能性治愈的热点，但存在疗效不确定、病毒反弹、耐药风险等挑战。2026年CROI大会报道了一项双bNABs（3BNC117-LS和10-1074-LS）的临床试验，结果显示有15人（54%）在停止ART治疗20周后仍未出现病毒反弹。双bNABs在一定程度上显示了延缓病毒反弹的潜力。免疫调节剂疗法通过调节机体免疫系统辅助抗病毒治疗是HIV/AIDS功能性治疗的另一大策略，在PD-1免疫检查点抑制剂基础上提高免疫调节治疗的疗效成为新的探索方向。2026年CROI大会报道的一项全球Ⅱ期随机对照试验，采用抗PD-1（budigalimab）联合抗α₄β₇整合素（trosunilimab）的策略，结果显示各组在反弹时间以及重启ART前的病毒载量峰值均无显著差异。α₄β₇整合素是淋巴细胞表面的重要黏附分子，介导淋巴细胞向肠道等组织的迁移，理论上抗α₄β₇整合能够与抗PD-1协同增强免疫作用，但该研究结果并未取得预期结果。潜伏病毒库研究潜伏病毒库是实现功能性治愈的核心障碍。2026年发表在《Nature》杂志上的一项研究成功分离出可不断增殖、持续产毒却不死亡的HIV潜伏库克隆（ARCs）。这些潜伏克隆平时对T细胞刺激不敏感，但在持续CTL压力下可被逐步清除。尤为重要的是，研究发现调节性T细胞来源的潜伏克隆存在可被药物逆转的免疫抗性。2026年CROI 大会报道的研究则发现其他清除潜伏病毒库的潜在策略。例如：（1）依非韦伦介导 CARD8 活化可以缩减HIV潜伏库，有6名接受依非韦伦治疗的参与者在4个月后的潜伏细胞减少了20%~50%；（2）N-803则是一种受体超激动剂，可促进NK和CD8细胞的增殖与功能，研究发现N-803可使完整HIV潜伏库一过性减少，并促使免疫细胞向干细胞样表型转化，但联合bNAbs未达到预期的 ART 中断后病毒控制效果。干细胞移植目前，全球已报道8例通过干细胞移植实现功能性治愈的HIV/AIDS患者，大多数患者接受的干细胞供体携带CCR5-Δ32纯合突变。 2025年《Nature》杂志报道了一例通过杂合型CCR5Δ32干细胞移植实现HIV-1持续6年缓解的案例；2024年《Nature Medicine》则报道了一例接受野生型CCR5供者移植的HIV感染者实现32个月持续病毒缓解。这些特殊的个案为扩大干细胞移植的适用范围提供了线索。长效ART预防近年来，随着药物递送技术取得突破性进展，众多长效ART的问世提供了新的长效预防方案。一项Ⅰ期开放研究对来那帕韦（Lenacapavir）的配方进行了升级，使其预防作用可持续长达一年。研究显示，每年一次肌肉注射与每年两次皮下注射的来那卡帕韦均能达到有效血浆浓度。这意味着，未来HIV预防可能从目前的每两个月一次注射进一步延长至每年一次，将极大提高高风险人群的依从性和预防覆盖率。新型长效INSTIs整合酶抑制剂（INSTIs）已成为当前ART方案的“主力军”，基于INSTIs的单片制剂虽然实现用药负担减小，当仍不能摆脱每日服药。2026年CROI大会报道的一项I期研究显示，VH-184作为第三代INSTI的应用前景可期，单次注射VH-184可维持药物体内浓度长达6至7个月，展现出每年两次给药的潜，且相较于当前常用的INSTI方案，VH-184在耐药HIV株中显示出更强的活性和更优化的耐药性特征。精英控制者的免疫机制精英控制者研究为理解HIV自然控制机制提供了独特窗口。2025年《Nature》杂志发表的研究揭示了CD8⁺T细胞干性在实现停药后病毒控制中的关键作用：在广谱中和抗体治疗后实现持久病毒控制的HIV感染者中，其CD8⁺T细胞在干预前即具备更强的增殖能力、干细胞样记忆表型和代谢适应性，而bNAb治疗可进一步增强这些特征。这表明，CD8⁺T细胞的干细胞样特性是实现HIV病毒血症干预后控制的前置条件。另一项发表于2025年《Nature》的研究进一步证实了这一发现。组合免疫疗法（疫苗＋bNAbs＋TLR9激动剂）可使70%的HIV感染者在停药后实现持续病毒控制，其作用机制在于：bNAb延缓病毒反弹，并为干细胞样CD8⁺T细胞的快速扩增争取了时间窗口。该研究在临床试验中验证了“诱导干细胞样CD8⁺T细胞”作为功能性治愈策略的可行性，为后续联合免疫治疗的设计提供了重要参考。02 HIV/AIDS功能性治愈的“深圳探索”近年来，作为国家感染性疾病临床医学研究中心主任，卢洪洲教授带领深三院团队在艾滋病功能性治愈领域进行了系统而深入的研究布局，形成了“学科-人才-项目-平台-成果-产品”一体化创新发展模式。在基础机制研究方面，团队聚焦于HIV储存库这一核心障碍，系统探索了潜伏病毒的生物学特征。通过对HIV病毒整合位点检测技术的优化，特别是LTA-PCR检测技术的建立，团队实现了对潜伏库的高灵敏度监测。研究还发现，加氧环化酶（IDO）与外周血HIV活跃程度呈正相关，可作为HIV感染者免疫标志物。在潜伏激活剂方面，团队首次报道了BMS-986158促进HIV-1潜伏激活的作用，为开发新型潜伏逆转剂提供了候选分子。相关成果发表于《Clinical Infectious Diseases》《mBio》《Clinical and Translational Medicine》《Pharmaceuticals》等国际期刊。在临床试验探索方面，团队开展了一系列国内首创的功能性治愈研究。其中，首个通过探索PD-L1抑制剂ASC22和潜伏逆转剂西达本胺联合治疗策略的临床试验，验证了两药联合激活HIV潜伏库的潜力，凸显了个体化免疫调控在HIV治疗中的应用前景。该研究已经发表在Nture旗下的《Signal Transduction and Targeted Therapy》（STTT）。团队还开展了国内首个基于新型RNA干扰技术的艾滋病功能性治愈临床试验（NCT03517631），共完成5例受试者的细胞回输治疗。该治疗策略利用慢病毒转导含7重折叠shRNA的CD34⁺细胞，这些shRNA可沉默CD4⁺T细胞的CCR5基因以及HIV复制必需的6个结构基因及调控基因。这一策略从两个维度同时攻击HIV：一方面阻断病毒进入宿主细胞（CCR5沉默），另一方面直接抑制病毒复制（针对HIV结构及调控基因），体现了多层次、多靶点的治疗理念。此外，团队还发起了一项HIV DNA疫苗治疗的临床研究，即抗病毒治疗中断（ATI）后治疗用艾滋病核酸注射液（ICVAX）对 HIV-1 感染者的安全性和有效性研究。在病毒学基础研究方面，团队针对中国5种主流HIV-1亚型（B、CRF01_AE、CRF07_BC、CRF08_BC、CRF55_01B），系统解析了gp140-CD4结合特性、Temsavir（一种新型HIV-1附着抑制剂）抑制效果及耐药机制。研究发现，B亚型gp140与CD4结合亲和力最强（KD=79 pM），而CRF重组亚型的结合力显著降低。尤为关键的是，Temsavir对B亚型的抑制率仅为35.7%。这一发现对于指导中国HIV感染者中Temsavir的临床应用具有重要意义，提示不同亚型对该药物的敏感性存在显著差异。团队还聚焦于HBV/HIV共感染、HBV/TB共感染、免疫重建不全等特殊人群的诊疗优化：（1）作为主要研究者参与了B/T/TAF一线治疗HBV/HIV共感染的全球多中心III期ALLIANCE研究，相关研究成果发表于《The Lancet HIV》。（2）团队首次采用350和500个/μL双CD4⁺ T细胞阈值定义免疫重建不全，系统分析了其与艾滋病定义性疾病和非艾滋病定义性疾病的长期关联，填补了免疫重建不全对非艾滋病定义性疾病影响的研究空白。（3）团队利用单细胞测序技术从外周血和肺泡灌洗液两个角度绘制了HIV-1/Mtb共感染人群的单细胞图谱，鉴定出可用于HIV-1和Mtb共感染的生物标志物。（4）此外，团队还针对HIV/AIDS患者的合并症管理、行为心理学调查等方面，优化HIV/AIDS患者的全方位身心干预策略。卢洪洲教授团队持续探索艾滋病功能性治愈新策略，从精准检测到全面评估，再到精准靶向治疗，有望在诸多领域实现更多“深圳案例”的突破。03 构建三位一体的综合性研究与转化模式卢洪洲教授指出，该团队在HIV/AIDS功能性治愈的全方位探索，建立于国家感染性疾病临床医学研究中心以及深圳国研中心四大基础科研平台（病原、免疫、测序与组学、病理）的建设，形成了完整的从基础科研到临床转化的技术链条，并有力推动了四大科研平台、临床队伍、企业转化方的协同与接洽，构建了三位一体的综合性研究与转化模式。2026年1月11日，由卢洪洲教授牵头承担的“新发突发与重大传染病防控”国家科技重大专项——“功能性储存库内潜伏病毒再激活的功能性治愈临床研究”项目正式启动，直指全球医学界长期面临的重大挑战。值得强调的是，卢洪洲教授团队的研究视野并不局限于HIV领域。在新冠疫情期间，团队发布了全球首篇新冠病毒全基因测序研究成果，揭示了临床结局相关的病毒和宿主因子，并主持了多项抗新冠病毒药物临床试验，助力小分子抗病毒药物成功上市。多项研究成果发表于NEJM、柳叶刀子刊、STTT等顶级期刊。团队因此荣膺诸多嘉奖和荣誉，如卢洪洲教授个人及团队先后荣获法国医学科学院夏邦克-杜博赛奖、荣获第十八届“药学发展奖·突出成就奖”、2025全球医疗科技创新转化奖，并收到国务院联防联控机制科研攻关组疫苗研发专班的感谢信。在医工融合领域，卢洪洲教授团队自主研发了医疗物联网非接触式ICU监护技术，在国际顶级期刊《IEEE Internet of Things》上发表，使临床医生能够及时远程评估ICU患者的生命体征状况，推动生命监护向“非接触式”变革发展。此外，团队还牵头开展了首台国产ECMO的临床验证研究，并致力于超级细菌噬菌体精准治疗的探索。04 总结和展望卢洪洲教授深耕感染和传染病防治事业近40年，从临床医疗到教学科研，从基础探索到成果转化，在艾滋病、新发突发传染病防治领域取得累累硕果，入选ScholarGPS 2024年全球前0.05%顶尖科学家榜单。在南下特区后，其带领的深圳团队以“亚洲一流、世界领先”为目标，按照医疗水平国际化、环境设施现代化、医疗服务精细化、诊疗流程规范化、运营管理智慧化的标准，构建集医疗、教学、科研、预防及预警预测为一体的国家感染性疾病临床医学研究中心和国家综合性区域医疗中心。在艾滋病功能性治愈这一全球性挑战面前，卢洪洲教授团队正以系统性的研究布局、前沿的技术平台和务实的临床转化，逐步揭开HIV潜伏病毒库的“黑色面纱”，力求实现艾滋病患者的功能性治愈乃至彻底治愈。正如卢教授在STTT发表文章时所言，“星星之火可以燎原”——每一份基础研究的突破、每一项临床试验的推进，都在为实现“红丝带”所象征的终结艾滋病流行的人类共同愿景贡献力量。卢洪洲教授深圳市第三人民医院党委副书记、院长传染和感染性疾病国家临床医学研究中心主任；南方科技大学医学院副院长、讲席教授；内科学、公共卫生管理与护理学博士生导师；美国微生物科学院fellow、深圳市首届疫情防控公共卫生专家组组长；教育部长江学者、国家百千万人才工程、“有突出贡献中青年专家”、享受国务院特殊津贴；深圳市国家级领军人才、上海领军人才；《iLABMED》主编；曾担任复旦大学附属华山医院院长助理、上海市公共卫生临床中心党委书记。入选美国斯坦福大学2021-2025年全球前2％顶尖科学家榜单及《终身科学影响力排行榜》、ScholarGPS终身与近5年全球前0.05%顶尖科学家榜单。学术任职世界卫生组织新发传染病临床诊治培训与研究合作中心主任；国际流感和呼吸道病毒感染学会(ISIRV)抗病毒小组(AVG)委员；国家疾病预防控制专家委员会委员，国家卫建委艾滋病、流感、埃博拉病毒病、感染病质量控制中心专家，国家新冠病毒病救治专家组与境外抗疫专家组后方支持团队成员中国性病艾滋病防治协会学术委员会副主任委员兼艾滋病合并结核专业委员会主任委员，中华医学会感染病学分会艾滋病专业学组副组长，中华医学会热带病与寄生虫分会前任主任委员兼艾滋病学组组长，欧美同学会（中国留学人员联谊会）医师协会传染病分会主任委员，上海市医学会感染病学分会前任主任委员广东省医学会微生态医学分会主任委员、深圳市医学会感染病分会主任委员、国家卓越期刊iLABMED主编科研成果先后承担国家科技重大专项(5项)，国家重点研发计划(2项)、“863”、国家自然科学基金 (9项，含2项重大研究项目)，美国盖茨基金、国家临床重点专科等63项科研课题以第一作者或通讯作者在国内外发表各类论文500余篇，其中包括在Nature、New England Journal of Medicine、Lancet Microbe、Signal Transduction and Targeted Therapy等SCI期刊发表论著360篇；已主编专业书籍15部；授权专利15项获奖荣誉法国国家科学院“夏邦克-杜博赛”奖(2020)，国家科学技术特等奖(2017)，中国药学发展奖“突出成就奖”(2024)、中华医学科技奖(2021)，上海市科技进步奖(2004,2009,2021)，上海市医学科技奖(2016)，上海市预防医学会科学技术奖(2021)、广东省优秀医药成果奖(2025)等国家及省部级科技成果奖10余项“人民名医∙卓越建树”奖(2022)，全国卫生系统先进个人、“最美援外医生”；联合国艾滋病规划署"精忠奖"等荣誉。

2026-05-08

·新药猎人笔记

EnGene暴跌80%！创新基因疗法膀胱癌关键试验12月CR数据急剧下降！

2026年5月8日，加拿大临床阶段基因疗法公司enGene Holdings（NASDAQ: ENGN）周四遭遇灾难性抛售，股价暴跌约80%，市值蒸发殆尽。导火索为其核心候选药物detalimogene voraplasmid（原代号EG-70）在关键性II期LEGEND试验中的最新中期数据更新，显示疗效持久性显著低于此前预期，令投资者对其商业化前景产生严重质疑。关键数据全面下滑 enGene于5月7日公布了LEGEND试验关键队列的更新中期数据。该试验针对高风险、卡介苗（BCG）无应答的非肌层浸润性膀胱癌（NMIBC）伴原位癌（CIS）患者。数据显示，任意时间点完全缓解率（CR）为54%，六个月CR率为43%，疾病进展至肌层浸润或更晚期的比率仅为3.2%。然而，真正引发市场恐慌的是耐久性指标。Kaplan-Meier法估算的12个月CR率仅为13%，中位缓解持续时间（DOR）为37.3周（约8.6个月），远低于公司内部预期及此前市场形成的乐观判断。虽然"Post-Protocol Amendment"整体数据（63%/62%）优于"Pre-Amendment"（55%/41%），但2025年10月后新入组的32例患者CR率断崖式下跌至39%和32%，几乎回到甚至低于早期水平。暗示疗效可能随时间推移或患者基线变化而衰减。尽管数据令人失望，enGene管理层仍试图维持乐观叙事，强调药物总体安全性良好、疾病进展率低，并表示将继续与FDA保持沟通，维持未来BLA申报的可能性。公司计划在2026年5月的一场重大泌尿外科学术会议上分享更多数据。竞争格局下的残酷现实彼时，enGene凭借非病毒基因递送平台DDX（Dually Derivatized Oligochitosan）的差异化优势——包括无需冷链储存、膀胱内灌注给药便捷、安全性良好（治疗相关不良事件率42%，3级以上仅2%）——被部分分析师视为NMIBC领域的潜在颠覆者。 NMIBC治疗领域近年来竞争急剧升温。强生的Inlexzo（吉西他滨膀胱内递送系统）已于2025年9月获批，其Sunrise-1试验中关键队列的任意时间CR率为82%，六个月CR率为59%，12个月CR率为46%。此外，Ferring的Adstiladrin（nadofaragene firadenovec，2022年获批）、ImmunityBio的Anktiva（nogapendekin alfa inbakicep，2024年获批）以及默沙东的PD-1抑制剂Keytruda均已占据市场先机。 enGene此前试图以"疗效相当但安全性更优"作为差异化卖点，但最新数据显示其12个月CR率（13%）与Inlexzo的46%存在显著差距，且近期入组患者应答率下滑的趋势，使其在疗效持久性这一关键维度上竞争力存疑。值得注意的是，就在数据公布前两天（5月5日），公司刚刚修订了首席医学官Hussein Sweiti的雇佣协议，允许其自6月1日起以五个工作日通知期辞职并保留离职后遣散费，这一人事条款的微妙调整在数据公布后显得意味深长。结束语： enGene的遭遇再次印证了临床阶段Biotech的残酷法则：在肿瘤免疫治疗领域，初步疗效数据带来的希望往往会被长期耐久性数据的现实击碎。对于BCG无应答NMIBC这一高度未满足需求的适应症，患者和医生需要的是能够长期维持缓解、避免膀胱切除（cystectomy）的疗法。detalimogene voraplasmid在短期应答率上尚具竞争力，但12个月CR率仅13%的表现，可能使其难以在Inlexzo等已获批疗法面前建立足够的临床价值主张。数据来源： enGene 2024全年财报及业务更新（Morningstar/Business Wire） enGene 2025年第三季度财报（Yahoo Finance/Business Wire） enGene 2026年第一季度财报（Morningstar/Business Wire） enGene LEGEND II期试验混合中期数据更新（TipRanks） EnGene与强生Inlexzo竞争对比分析（Oncology Pipeline） enGene膀胱癌基因疗法试验为申报铺路（Pharmaphorum） Endpoints News关于enGene股价暴跌的报道 Investing.com关于enGene 54%应答率的报道 enGene 2025全年财报及业务更新（Onyx Newsroom）

2026-05-08

·allsci.com

enGene reports 54% CR in NMIBC pivotal cohort, but 12-month durability remains limited at 25%

Boston-based biotech enGene Therapeutics (Nasdaq: ENGN) reported updated interim data from the pivotal cohort of its LEGEND trial showing detalimogene voraplasmid (formerly known as EG-70) achieved a 54% complete response rate at any time in BCG-unresponsive non-muscle invasive bladder cancer, though a Kaplan-Meier estimate of 12-month duration of response of 25% raises questions about durability that the company acknowledged will require further evaluation. The LEGEND trial is an ongoing, open-label, multi-cohort Phase II study evaluating detalimogene voraplasmid — a non-viral, intravesical gene-based immunotherapy — in patients with high-risk, BCG-unresponsive NMIBC with carcinoma in situ (CIS), with or without concomitant papillary disease. The pivotal cohort, Cohort 1, enrolled 125 patients and is designed to serve as the basis for a planned Biologics License Application (BLA) filing. The data cutoff for this interim analysis was April 21, 2026. The trial also includes three additional cohorts: BCG-naïve NMIBC patients with CIS, BCG-exposed but inadequately treated CIS patients, and BCG-unresponsive patients with papillary-only disease — a breadth of design that, if supported by data, could underpin a broader label than any currently approved agent in this setting. In the 125-patient pivotal cohort, 67 of 124 evaluable patients achieved a complete response at any time, yielding a CR rate of 54% (95% CI: 45%, 63%). Of these, 91% of responses occurred at the first disease assessment. The six-month CR rate was 43% (95% CI: 34%, 52%) based on 52 of 121 evaluable patients, with 14% of non-responders converting to CR after re-induction. Among the 52 patients who achieved a CR at six months, 37 of 44 with a nine-month assessment remained in CR. At 12 months, 13 of 22 patients with an assessment were still in CR, with 11 additional patients pending evaluation. The Kaplan-Meier estimate of 12-month duration of response was 25% (95% CI: 11%, 41%), with a median duration of response of 37.3 weeks (range: 31.6–43.9 weeks). The rate of progression to muscle-invasive or more advanced disease was 3.2%, a figure enGene cited as clinically meaningful given that bladder preservation is a central goal in this population. A notable finding within the interim data is that the 32 patients whose first disease assessment occurred after the October 24, 2025 data cutoff showed lower CR rates than the overall cohort — 39% at any time and 32% at six months. The company said a preliminary subgroup analysis had not identified material differences in demographics or disease characteristics, and that a more comprehensive analysis was ongoing. The tolerability profile was consistent with prior reports. Of the 125 patients assessed for safety, 55% experienced at least one treatment-related adverse event, with 91% of those events graded as Grade 1 or 2. Grade 3 TRAEs occurred in six patients (4.8%), and one Grade 4 TRAE was reported, which resolved. No Grade 5 events were observed. Treatment interruption and discontinuation due to TRAEs each occurred in 2.4% of patients. The most common TRAEs were fatigue (22%), dysuria (14%), micturition urgency (12%), pollakiuria (12%), and bladder spasm (11%). Detalimogene voraplasmid is designed for intravesical instillation and uses enGene’s proprietary Dually Derivatized Oligochitosan (DDX) platform, a non-viral delivery technology intended to penetrate mucosal tissues and transfect urothelial cells with plasmid DNA. The mechanism centers on local innate immune activation, including IL-12 expression and downstream IFN-γ-associated antitumor immune signaling, with the goal of generating a potent but spatially confined anti-tumor immune response within the bladder. The non-viral nature of the delivery system is a key differentiator from Ferring’s Adstiladrin (nadofaragene firadenovec), which uses a recombinant adenoviral vector encoding IFN-α2b. Adenoviral approaches may be subject to pre-existing anti-vector immunity, and their cold-chain handling requirements add logistical complexity in urology clinic settings. Detalimogene, by contrast, is positioned as a simpler-to-handle intravesical monotherapy. The non-muscle invasive bladder cancer therapy landscape has expanded considerably in recent years. Four agents now carry FDA approval specifically for BCG-unresponsive NMIBC with CIS: Merck’s Keytruda (pembrolizumab), approved in January 2020 with a CR rate of approximately 41% in the KEYNOTE-057 trial; nadofaragene firadenovec, approved in December 2022 with a CR rate of approximately 53% at three months; ImmunityBio’s Anktiva (nogapendekin alfa inbakicept-pmln), approved in April 2024 with a reported CR rate of 62% in the QUILT-3.032 trial, used in combination with BCG; and Janssen’s Inlexzo (gemcitabine intravesical system), approved in September 2025. Cross-trial comparisons are limited by differences in patient populations, eligibility criteria, response assessment schedules, and follow-up durations. Direct efficacy benchmarking between detalimogene and these approved agents is not possible from available data. However, within this field, detalimogene’s potential differentiation rests primarily on its non-viral delivery modality, its monotherapy design that does not require BCG co-administration — unlike nogapendekin alfa inbakicept-pmln — and its intravesical route, which avoids the systemic immune-related adverse event profile associated with pembrolizumab. The durability question, however, is one that applies broadly across the class, and the 25% Kaplan-Meier 12-month duration of response estimate from the LEGEND pivotal trial interim results will need to mature before the full durability picture becomes clear. Detalimogene holds both Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations from the US FDA, and has been selected for the agency’s CMC Development and Readiness Pilot (CDRP) program. enGene said it has completed required FDA manufacturing validation batches and submitted a Statistical Analysis Plan to the agency. The company plans to present the LEGEND pivotal trial results at a plenary session of the American Urological Association meeting on May 15, 2026, and indicated it will provide a further regulatory update in the second half of 2026 as it approaches a potential BLA filing. This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/ Your email address will not be published. Required fields are marked * Comment * Name * Email * Website Privacy Terms About Us Copyright © 2026. AllSci Corp. All rights reserved.

100 项与诺格白介素α-因奇西普相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D12888	-	-	-

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
转移性非小细胞肺癌	沙特阿拉伯	ImmunityBio, Inc.	2026-04-21
原位癌	欧盟	ImmunityBio, Inc.	2026-02-16
原位癌	冰岛	ImmunityBio, Inc.	2026-02-16
原位癌	列支敦士登	ImmunityBio, Inc.	2026-02-16
原位癌	挪威	ImmunityBio, Inc.	2026-02-16
非肌层浸润性膀胱尿路上皮癌	沙特阿拉伯	ImmunityBio, Inc.	2026-01-14
淋巴细胞减少	美国	ImmunityBio, Inc.	2025-06-02
非肌层浸润性膀胱肿瘤	美国	Altor BioScience Corp.	2024-04-22

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适应症	最高研发状态	国家/地区	公司	日期
社区获得性肺炎	临床3期	-	ImmunityBio, Inc.	2026-04-15
急性呼吸窘迫综合征	临床3期	-	ImmunityBio, Inc.	2026-04-15
脓毒症	临床3期	-	ImmunityBio, Inc.	2026-04-15
脓毒性休克	临床3期	-	ImmunityBio, Inc.	2026-04-15
肺癌	临床3期	美国	ImmunityBio, Inc.	2022-07-27
晚期非小细胞肺癌	临床3期	美国	ImmunityBio, Inc.	2018-05-18
膀胱癌	临床3期	美国	ImmunityBio, Inc.	2017-06-02
免疫抑制	临床2期	-	ImmunityBio, Inc.	2026-07-06
复发性非小细胞肺癌	临床2期	美国	ImmunityBio, Inc.	2026-03-31
前列腺腺癌	临床2期	-	ImmunityBio, Inc.	2025-12-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT06745908 (ResQ201A, ESMO_ELCC2026)	临床3期	-	462	NAI+tislelizumab+docetaxel	壓選艱獵範鏇範網壓蓋(顧遞醖願醖廠壓艱壓蓋) = 構糧蓋觸構範壓糧衊願艱願鑰餘衊蓋壓壓築憲 (壓構鏇觸餘鬱製襯齋獵 ) 更多	积极	2026-03-25
				docetaxel	壓選艱獵範鏇範網壓蓋(顧遞醖願醖廠壓艱壓蓋) = 選糧簾網膚衊廠積範廠艱願鑰餘衊蓋壓壓築憲 (壓構鏇觸餘鬱製襯齋獵 ) 更多
NCT02523469 (CTgov)	临床1/2期	转移性非小细胞肺癌	67	ALT-803+Nivolumab (Cohort 1: ALT-803 6 µg/kg + Nivolumab 3 mg/kg)	膚獵襯衊鹽鬱衊遞構廠 = 襯顧淵遞齋齋選願鏇鏇遞鬱顧醖網顧鬱醖獵艱 (廠願廠衊壓艱觸簾齋顧, 廠餘鏇範窪獵繭壓餘簾 ~ 齋鏇鹽醖壓醖淵襯網膚) 更多	-	2026-02-17
				ALT-803+Nivolumab (Cohort 2: ALT-803 10 µg/kg + Nivolumab 3 mg/kg)	膚獵襯衊鹽鬱衊遞構廠 = 憲鹹艱願淵製憲遞遞顧遞鬱顧醖網顧鬱醖獵艱 (廠願廠衊壓艱觸簾齋顧, 繭鏇鏇憲淵鹽艱願餘繭 ~ 選壓壓範獵觸衊網積積) 更多
NCT04491955 (Pubmed \| Oncologist)	临床1/2期	转移性结直肠癌 pMMR	32	CV-301 + N-803 + bintrafusp alfa + PDS01ADC	鹽窪鑰廠簾製襯築網廠(製鹽鏇膚鬱齋膚齋餘簾) = 夢製艱網繭餘憲鹽襯製齋襯簾願遞衊網觸鹽醖 (蓋壓鑰壓遞構淵艱築餘 ) 更多	不佳	2026-02-05
NCT03228667 (QUILT-3.055, Company_Website) 人工标引	临床2期	非小细胞肺癌二线	-	ANKTIVA + CPI (NSCLC)	鏇衊願鬱簾廠願蓋願廠(憲範蓋鏇顧夢願繭觸網) = 獵鹹鏇網觸構蓋遞鏇鑰範獵襯顧淵積艱築膚廠 (鹹憲鹹壓製憲願構觸選 )	积极	2026-01-13
				ANKTIVA + CPI (NSCLC + Responders)	觸糧餘醖衊壓鬱範遞鏇(鏇鏇壓鑰醖製憲鑰願艱) = 範繭選範醖製艱願窪獵觸艱夢齋壓壓艱觸簾積 (獵鏇膚鑰網糧廠廠齋膚 )
NCT03520686 (QUILT-2.023, Company_Website) 人工标引	临床3期	转移性非小细胞肺癌 \| 晚期非小细胞肺癌一线	-	ANKTIVA + CPI	糧構願顧窪憲鹽積齋選(簾鏇鏇壓醖壓廠夢鏇願): P-Value = 0.0065	积极	2026-01-13
				CPI
NCT03022825 (QUILT-3.032, Pubmed \| J Urol)	临床2期	-	54	NAI plus BCG (BCG-unresponsive high-grade Ta/T1 papillary nonmuscle-invasive bladder cancer)	餘鬱遞衊願衊簾壓窪鑰(蓋選淵鬱製鏇獵獵獵鹽) = 遞壓築鑰淵齋鏇襯餘蓋壓鬱鏇艱簾夢糧積憲襯 (範獵衊齋網遞範鑰選鹹, 46.6 ~ 68.2) 更多	积极	2026-01-01
NCT03493945 (QuEST1, SITC2025)	临床1/2期	去势抵抗性前列腺癌	37	BNVax+BA+NAI	範憲壓襯膚觸膚製鑰範(積製鏇糧醖構餘醖遞窪) = 範範憲膚觸積蓋鹽築鬱範衊膚襯遞壓夢願餘製 (簾餘鹹夢積醖築範遞鬱 )	积极	2025-11-05
NCT03022825 (QUILT-3.032, Pubmed \| J Urol)	临床2期	-	54	NAI plus BCG (BCG-unresponsive high-grade Ta/T1 papillary nonmuscle-invasive bladder cancer)	願艱繭製襯壓願鏇襯膚(憲遞獵艱壓憲構選獵襯) = 廠窪觸餘選製糧憲醖繭窪鏇艱願鏇淵鬱積鏇糧 (鹽醖鏇遞廠製顧鏇憲範, 46.6 ~ 68.2) 更多	积极	2025-11-03
NEWS 人工标引	N/A	复发性胶质母细胞瘤	5	Anktiva	遞膚窪積選顧齋廠醖壓(積顧顧網襯壓壓衊積襯) = 衊衊繭願憲鹹廠襯膚選鑰齋鹹壓衊繭壓範獵顧 (餘蓋積鑰製繭鏇積壓構 )	积极	2025-08-29
NCT03493945 (QuEST1, CTgov)	临床1/2期	局部晚期恶性实体瘤 \| 晚期恶性实体瘤	59	castration+M7824+BN-Brachyury (Phase IIA Dose Expansion (Dose Exp.), Cohort 2, Arm 2.1A)	繭鏇齋簾製製願醖憲廠 = 願鏇鹹顧壓廠窪醖鏇廠鬱鏇鑰鏇餘夢積製壓夢 (鑰蓋築鹽觸廠鬱衊齋壓, 繭窪壓簾醖鏇蓋鏇鹽鹹 ~ 積齋繭餘觸齋襯窪鏇齋) 更多	-	2025-06-08
				N-803+N803+M7824+BN-Brachyury (All Participants in Phase IIA Dose Expansion and Phase IIB Dose Expansion)	繭鏇齋簾製製願醖憲廠 = 鑰鑰築遞選淵繭齋醖顧鬱鏇鑰鏇餘夢積製壓夢 (鑰蓋築鹽觸廠鬱衊齋壓, 製積餘顧構窪選窪糧膚 ~ 膚鏇餘繭獵餘齋醖廠齋) 更多