A Phase II, Open-Label, Multicenter Study of Inobrodib in Combination With Pomalidomide and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

The purpose of this study is to learn more about the anti-cancer activity of inobrodib, when given in combination with pomalidomide and dexamethasone, in patients with multiple myeloma that has come back following treatment and which no longer responds to available therapies. The study treatment will not be compared to any other treatment and patients will know what treatment they are receiving. This study will also further explore the side effects of inobrodib in combination with these other medicines.

开始日期2025-12-01

申办/合作机构

CellCentric Ltd.

KCT0010365

/ Not yet recruiting临床1期IIT

Phase I study of pomalidomide-R-CHOP for patients with newly diagnosed diffuse large B-cell lymphoma who are at high risk of central nervous system relapse

开始日期2025-08-01

申办/合作机构

Asan Medical Center

NCT07018050

/ Not yet recruiting临床2期

A Multicenter, Open-Label Phase II Study to Evaluate QLS32015 Combination Therapy in the Treatment of Multiple Myeloma

The purpose of the study is to compare the efficacy of QLS32105 (SC) in combination with Pomalidomide, and QLS32105 (SC) in combination with QL2109 or Daratumumab, and QLS32105 (SC) in combination with QL2109 or Daratumumab and Pomalidomide, and QLS32105(SC) in combination with Bortezomib and Lenalidomide.

开始日期2025-07-01

申办/合作机构

齐鲁制药有限公司

100 项与泊马度胺相关的临床结果

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100 项与泊马度胺相关的转化医学

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100 项与泊马度胺相关的专利（医药）

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2,799

项与泊马度胺相关的文献（医药）

2025-09-01·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Reversing an agonist into an inhibitor: Development of mTOR degraders

Article

作者: Li, Ruichen ; Zhu, Liquan ; Chen, Zhe ; Zhou, Yiyu ; Fu, Siyi ; Meng, Xuli ; Ma, Longfei ; Zeng, Qian ; Qian, Huijuan ; Ge, Jingyan

Targeted protein degradation using proteolysis-targeting chimeras (PROTACs) has emerged as a powerful strategy for modulating protein function. In this study, we developed mTOR-targeting PROTACs by conjugating the mTOR agonist MHY-1485 to the Cereblon (CRBN) ligand pomalidomide, demonstrating that even activators can serve as effective warheads for targeted protein degradation. Through systematic screening, we identified PD-M6 as a potent bifunctional molecule capable of degrading mTOR (DC₅₀ = 4.8 μM), reversing the proliferative effects of MHY-1485, and inhibiting cell proliferation (IC₅₀ = 11.3 μM) while inducing autophagy, akin to the mTOR known inhibitor rapamycin. Proteomic analysis further revealed that PD-M6 downregulated key proteins in the mTOR signaling pathway, including LAMTOR1, MAPKAP1, and CASTOR1, which are involved in proteasome-mediated degradation, cell division, apoptosis, and lysosomal signaling. Notably, PD-M6 specifically induced the degradation of LAMTOR1. These findings highlight a novel approach for designing PROTACs from agonists, broadening the scope of targeted protein degradation strategies for therapeutic applications.

2025-08-01·JOURNAL OF CLINICAL ONCOLOGY

Isatuximab Subcutaneous by On-Body Injector Versus Isatuximab Intravenous Plus Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Phase III IRAKLIA Study

Article

作者: Suzan, Florence ; Koch, Victorine ; Li, Fei ; Dimopoulos, Meletios-Athanasios ; Schjesvold, Fredrik ; LeBlanc, Richard ; Leleu, Xavier ; Sémiond, Dorothée ; Buck, Tondre T. ; Lu, Jin ; Goldschmidt, Hartmut ; Custidiano, Maria del Rosario ; Li, Chunrui ; Zhang, Rick ; Stefanova-Urena, Maya ; Hus, Marek ; Ling, Silvia ; Ailawadhi, Sikander ; Gomez, Cesar ; Oriol, Albert ; Spencer, Andrew ; Cerchione, Claudio ; Parmar, Gurdeep ; Mateos, Maria Victoria ; Hungria, Vania ; Moreau, Philippe ; Ishida, Tadao ; Špička, Ivan ; Beşışık, Sevgi Kalayoğlu ; Minařík, Jiří ; Berkovits, Alejandro ; Rajnics, Péter

PURPOSE:

To report the results of the multicenter, open-label IRAKLIA trial (ClinicalTrials.gov identifier: NCT05405166 ) of isatuximab subcutaneous (SC) versus intravenous (IV), plus pomalidomide and dexamethasone, in relapsed/refractory multiple myeloma (MM), to our knowledge, the first phase III MM trial using an on-body injector (OBI).

METHODS:

Patients with ≥1 prior line of therapy were randomly assigned 1:1 to Isa OBI (1,400 mg) or IV (10 mg/kg) once weekly in cycle (C)1 and then every 2 weeks, plus pomalidomide (4 mg once daily, day [D]1-21) and dexamethasone (40 mg once weekly [age ≥75: 20 mg]) and treated until progression, unacceptable toxicity, or patient request. Coprimary end points were overall response rate (ORR; noninferiority margin, 0.839) and Isa C trough (C6D1 predose; noninferiority margin, 0.8). Noninferiority of OBI versus IV was demonstrated if both coprimary end points achieved noninferiority.

RESULTS:

IRAKLIA randomly assigned 531 patients (OBI, n=263; IV, n=268). After 12-month median follow-up, the ORR was 71.1% (OBI) and 70.5% (IV; relative risk, 1.008 [95% CI, 0.903 to 1.126]; lower CI exceeded noninferiority margin). The mean (standard deviation) C6D1 C trough was 499 (259) μg/mL (OBI) and 340 (169) μg/mL (IV). The C trough geometric mean ratio (90% CI) was 1.532 (1.316 to 1.784); lower CI exceeded noninferiority margin. Grade ≥3 treatment-emergent adverse event incidences were 81.7% (OBI) and 76.1% (IV); infusion reaction incidences were 1.5% and 25.0%. Injection site reactions occurred in 0.4% of OBI injections (all grade 1-2); 99.9% of injections completed without interruption.

CONCLUSION:

IRAKLIA demonstrated efficacy and pharmacokinetic noninferiority between Isa OBI and IV. No unexpected safety signal was observed, with excellent local tolerability of Isa OBI. Efficacy and safety were comparable with Isa IV in ICARIA-MM, except the lower OBI infusion reaction rate. These results support potential use of the OBI, designed to improve practice efficiency.

2025-08-01·PHARMACOLOGICAL RESEARCH

Trend in the use of biological drugs in pediatric patients with immune-mediated inflammatory diseases: Insight from the large-scale Italian VALORE project

Article

作者: Rossi, Paola ; Trama, Ugo ; Massari, Marco ; Carta, Paolo ; Senesi, Ilenia ; Belleudi, Valeria ; Spini, Andrea ; Costa, Giorgio ; Carollo, Massimo ; Soardo, Federica ; Lopes, Sara ; Scarpelli, Rita Francesca ; Balducci, Francesco ; Mangano, Antea Maria Pia ; De Sarro, Giovambattista ; Gini, Rosa ; Spila Alegiani, Stefania ; Bucaneve, Giampaolo ; Bellitto, Chiara ; Bernardi, Francesca Futura ; Ejlli, Lucian ; Gallizzi, Romina ; Urru, Silvana Anna Maria ; Scapin, Angela ; Ingrasciotta, Ylenia ; Trifirò, Gianluca ; Da Cas, Roberto ; Tuccori, Marco ; Puccini, Aurora ; Ledda, Stefano ; Mazzone, Arianna ; Ancona, Domenica ; Cavazzana, Anna ; Sorrentino, Carla ; L'Abbate, Luca ; Pellegrini, Giorgia ; Stella, Paolo ; Allotta, Alessandra ; Leoni, Olivia ; Pollina, Sebastiano Addario ; Sapigni, Ester ; Mathieu, Clément ; Campomori, Annalisa

Real-world data on biological drug use in pediatric patients with immune-mediated inflammatory diseases (IMIDs) are scarce. This retrospective, population-based, cohort study aimed to provide an overview of biological drug use among children and adolescents with IMIDs from 2010 to 2023 using the Italian VALORE distributed database network. As secondary aim, potential of such a network for evaluating the risk of serious infections related to biological drugs in pediatrics was investigated. The yearly prevalence of use of biological drugs in IMID pediatric patients was calculated. Among incident users, persistence to adalimumab, etanercept, infliximab, golimumab, tocilizumab, secukinumab, and abatacept was measured. A sample power analysis to estimate the person-years of exposure required to investigate the association with the risk of serious infection and individual biological drug was performed. The yearly prevalence of biological drug use increased over time (+427.3 %), and it was consistently higher among females than males and among 12-17-year-olds than younger children. A total of 6222 incident biological drug users were identified, with a median follow-up of 3.8 years, and juvenile idiopathic arthritis (JIA, 35.9 %) and inflammatory bowel diseases (IBDs, 35.9 %) were the most common indications for use. After one year from the treatment start, more than 70 % of JIA patients using either adalimumab or etanercept were still on treatment, while persistence rates in IBDs were lower (ranging from 57.4 % to 65.0 %). Findings of this study show the potential of the VALORE network to provide enough exposure data to investigate the risk of serious infections for adalimumab, etanercept, and infliximab.

885

项与泊马度胺相关的新闻（医药）

2025-08-02

·精准药物

【JMC】中国学者报道一类新型、强效IKZF1/2/3三重分子胶降解剂

近日，来自国家应急防控药物工程技术研究中心，国家安全特需药品全国重点实验室的研究团队与华北理工大学研究团队合作在国际权威药物化学期刊《Journal of Medicinal Chemistry》上发表了一篇题为“Discovery of Novel Potent Triple IKZF1/2/3 Degraders for the Treatment of Hematological Cancers”的研究论文（DOI: 10.1021/acs.jmedchem.5c01086）。该研究通过系统的理性设计及构效优化、体外/体内机制验证及小鼠模型疗效评估，获得全新酞嗪酮为骨架的新型强效IKZF1/2/3三重分子胶降解剂MGD-22，可显著抑制肿瘤生长（TGI达97.28%），无明显毒性，且与布鲁顿酪氨酸激酶（BTK）抑制剂和B细胞淋巴瘤-2（BCL-2）抑制剂联合使用时具有显著的协同效应。该研究为血液系统癌症治疗提供了新候选药物和多靶点降解策略，为克服现有度胺药物耐药性提供了的新解决方案。01 研究背景：传统度胺类药物的困境与突破方向分子胶降解剂是一类能够诱导蛋白质-蛋白质相互作用（PPI），利用人体内天然存在的泛素-蛋白酶系统特异性地靶向降解某种疾病相关蛋白的小分子化合物 [1]。血液肿瘤的发生与发展，常与造血细胞中关键转录因子的异常激活密切相关。其中，IKZF家族（IKZF1、IKZF2、IKZF3）作为重要的锌指转录因子，在造血系统发育和肿瘤细胞生存中起关键作用[2]。传统度胺类药物（IMiDs）如沙利度胺、来那度胺、泊马度胺通过招募CRBN形成 E3 连接酶复合物，诱导IKZF1、IKZF3等转录因子降解发挥作用，广泛用于血液系统癌症（如多发性骨髓瘤（MM）、急性髓系白血病（AML）、弥漫性大 B 细胞淋巴瘤（DLBCL）等）治疗，但现有 IMiDs 及下一代 CELMoDs（如 CC-220、CC-885、CC-82480）因结构相似性易引发耐药，其次血液毒性（如中性粒细胞减少、肝损伤）等问题限制临床应用，需开发新型 CRBN 调节剂以拓展治疗潜力 [3]。02 研究内容① 全新骨架先导物发现与结构优化从 160 余万个化合物中筛选出含戊二酰亚胺结构的候选分子，通过表型筛选发现phthalazinone（酞嗪酮）骨架（如 MGD-1f）相比传统邻苯二甲酰亚胺，能更高效结合CRBN与IKZF家族蛋白，同时诱导IKZF1/2/3降解，尤其对IKZF2的降解活性提升显著，而 IKZF2 在白血病干细胞存活、肿瘤进展中至关重要 [4]。MGD-1f在急性髓系白血病（MV-4-11）细胞中IC50 < 1 μM，且对IKZF2降解率（27.7%）显著高于泊马度胺（< 10%）。分子对接显示，MGD-1f 能占据CRBN与IKZF2的结合界面，促进三元复合物的形成。为提升MGD-1f的活性，研究团队开展“结构-活性关系（SAR）”分析，通过修饰分子结构增强与靶蛋白的相互作用：l环结构调整：将MGD-1f 酞嗪酮环中的碳氮双键（C=N）还原为单键（C-N），得到MGD-3a，增加分子柔性；进一步引入甲基（MGD-3b），利用疏水作用增强与CRBN的结合，对IKZF2降解率提升至48.4%，对多发性骨髓瘤（NCI-H929）细胞的IC50降至0.379 μM。l取代基优化：在酞嗪酮的5位引入芳香胺基团（如MGD-4），通过π-π堆叠作用增强与IKZF2的结合，对IKZF2降解率大于50%；延长侧链并引入甲基苯（MGD-15），对IKZF2降解率提升至70%，对弥漫性大B细胞淋巴瘤（WSU-DLCL-2）细胞的IC50降至0.172 μM；l侧链拓展：在MGD-15的结构基础上引入吗啉、哌嗪等基团，进一步增强与 IKZF2的π-π堆叠作用（如MGD-18），进一步增强对IKZF1/2/3的降解作用，对NCI-H929和WSU-DLCL-2细胞的IC50降至0.0299和0.0805 μM；(A) Substrate scope of glutarimide analogues, thalidomide, lenalidomide and pomalidomide in IKZF1, IKZF2 and IKZF3 in engineered HEK293T cells using the respective HiBit assays. Cells were treated with 1 μM concentration of each compound for 24 h. (B) The docking model of MGD-1f to the IKZF2 (orange)-CRBN (green) derived from the Protein Data Bank (PDB: 7LPS).② 高效抑制肿瘤，克服耐药性经过多轮优化最终获得MGD-22，通过独特的分子结构稳定结合CRBN，脂肪族叔胺与CRBN的Glu377形成盐桥，增强结合亲和力，进而招募 IKZF1/2/3实现“三重降解”，且活性达到纳摩尔级别。MGD-22抑制NCI-H929、MV-4-11、WSU-DLCL-2细胞增殖IC50值为0.005-0.009 μM，远优于传统药物，且对泊马度胺耐药的肿瘤细胞仍有效（IC50值为0.04-0.08 μM）。对正常细胞如外周血单核细胞（PBMCs）、原代B细胞毒性低，IC50 > 33 μM。Evaluation of analogues MGD-16 to MGD-22. (A) The binding mode of MGD-15 interacts to the IKZF2-CRBN. PDB ID: 7LPS. (B) IC50 values of Chemical structures of MGD-15-based derivates (MGD-16 to MGD-22), lenalidomide (Len) and pomalidomide (Pom) in NCI-H929, MV-4-11 and WSU-DLCL-2 cells for 96 h. (C) Substrate scope of analogues MGD-16 to MGD-22, lenalidomide (Len) and pomalidomide (Pom) in IKZF1, IKZF2 and IKZF3 in engineered HEK293T cells using the respective HiBit assays. (D) Model of IKZF2 (orange), CRBN (green), and MGD-22 projecting a π-π system cloud from an aromatic substitution. The model was derived from PDB: 7LPS. (E) Western blot analysis of Ikaros family members in NCI-H929 (left) and MV-4-11 (right) cells treated with indicated doses of MGD-20, MGD-21, MGD-22 and pomalidomide (Pom) for 24 h.③ 精准高效降解靶点，机制明确蛋白组及IKZFs-HiBit定量模型结果表明，MGD-22特异性诱导IKZF1/2/3降解，对IKZF1/2/3的半数降解浓度（DC50）值分别为8.33 nM、9.91 nM、5.74 nM，24小时内可降解超过90%的靶蛋白，选择性优异。CRBN敲除细胞中MGD-22丧失降解能力，蛋白酶体抑制剂（MG132），泛素激活酶（E1）酶抑制剂（TAK-243）或NEDD8 活化酶 (NAE) 抑制剂（MLN4924）阻断降解选择性降解，表明MGD-22通过Cullin-CRBN通路诱导IKZF1/2/3的降解。MGD-22 selectively induces significant degradation of Ikaros proteins. (A) Proteomics analysis of NCI-H929 cells treated for 4 h with MGD-22 (1 μM) or DMSO. (B) Heatmap showing the ratio of global neosubstrates in whole-proteome quantification. (C) Levels of IKZF1, IKZF2 and IKZF3 in engineered HEK293T (293T) cells with increasing doses of MGD-22 for 24 h as determined by IKZF1-, IKZF2- and IKZF3-HiBit assay, respectively. (D) Levels of IKZF1, IKZF2 and IKZF3 in engineered HEK293T cells with increasing treatment time of MGD-22 (1 µM) as determined by IKZF1-, IKZF2- and IKZF3-HiBit assay, respectively. MGD-22 induces significant degradation of Ikaros proteins via the Cullin-CRBN dependent pathway. (A) Viability of control vector and CRBN−/− NCI-H929 cells treated with MGD-22 for 96 h. (B) Western blot analysis of IKZF1, IKZF2 and IKZF3 degradation in NCI-H929 cells CRBN knockout, pre-treated with TAK-243 (1 µM), MLN4924 (1 µM) or MG132 (1 µM) for 1 h and treated with MGD-22 (1 µM) for 24 h. C. Viability assay performed in MV-4-11 cells treated with increasing doses of MGD-22 for 96 h in the absence and presence of pomalidomide (Pom, 10 µM). (D, E) Flow cytometry plot showing control vector and CRBN−/− NCI-H929 cells treated with indicated doses of MGD-22 or pomalidomide (Pom) for 3 days, and cells were stained with Annexin V-PE and DAPI (D). Apoptosis was measured by flow cytometry using Annexin V as a marker (E). ⑤ 体内疗效显著，药代性质及安全性良好在NCI-H929小鼠异种移植模型中，MGD-22（10mg/kg，口服）的肿瘤生长抑制率（TGI）达97.28%，显著优于传统药物泊马度胺（69.74%），肿瘤组织Western blot证实IKZF1/2/3降解。长期给药后，小鼠体重无明显下降，无严重毒性反应。MGD-22药代性质良好，口服生物利用度39.4%，达峰时间（Tmax）1.0 h，清除率和分布容积适中。MGD-22 exhibited high efficiency in MM tumor xenograft. (A) Treatment schedule for the NCI-H929 cells xenograft tumors model treated with vehicle, pomalidomide and MGD-22, respectively. (B, C) Immunodeficiency NOD/SCID mice transplanted with NCI-H929 cells were orally administrated vehicle control, pomalidomide (Pom) or MGD-22 with single doses of 3 mg/kg or 10 mg/kg for 14 days. The change of NCI-H929 tumor volume (B) and change of body weight (C) of all mice in each group were shown (n = 8 per group). (D) Tumor volumes and TGI after treatment for 14 days of each group in (B) are shown. (E, F) Representative images of H&E, Ki67, and cleaved-caspase 3 immunohistochemical (IHC) staining in harvested tumors from each group in (B) are shown (E). Histograms show the quantification of Ki67+ and cleaved-caspase 3+ cells (F). (G) Western blot analysis of CRBN, IKZF1, IKZF2 and IKZF3 in harvested tumors or their mixture (#M, n = 8) from each group were shown.⑥ 协同治疗增效，拓宽应用场景研究发现，MGD-22与现有靶向药物BTK抑制剂（伊布替尼）、BCL-2抑制剂（维奈托克）联合使用时，协同评分（SS）均超10，在弥WSU-DLCL-2模型中，TGI达92.69%，显著高于单药（MGD-2单药77.47%，伊布替尼单药46.71%）；与BCL-2抑制剂（维奈托克）联合TGI达97.76%，显著高于单药维奈托克（61.88%）且显著延长小鼠生存期。Synergetic effect of MGD-22 with standard therapeutic agents in inhibiting DLBCL cell growth. (A, B) Effect of MGD-22, Ibrutinib, Venetoclax or drug combination on viability of WSU-DLCL-2 cells (A). Three-dimensional synergy score heatmaps for MGD-22 plus Ibrutinib (left) or Venetoclax (right) in WSU-DLCL-2 cells calculated using SynergyFinder (B). (C) Treatment schedule for the WSU-DLCL-2 cells xenograft tumors model treated with vehicle, MGD-22, Ibrutinib, Venetoclax or drug combination. (D, F) NOD/SCID mice transplanted with WSU-DLCL-2 cells were orally administrated with single agent MGD-22, Ibrutinib, Venetoclax or combinational treatment of MGD-22 + Ibrutinib and MGD-22 + Venetoclax for 36 days. The change of WSU-DLCL-2 tumor volume (D) of all mice in each group were shown. Tumor volumes and TGI after treatment for 21 days of each group in (C) are shown (n = 7 per group). Change of body weight (F) of all mice in each group were shown (n = 7 per group). (G) Survival rates for mice treated as in (C) were shown (log-rank test; n = 7 per group). 03 研究总结：为血液肿瘤提供新的治疗策略本研究发现了一种新型强效IKZF1/2/3三靶点分子胶降解剂MGD-22，其在多种血液瘤细胞中展现出纳摩尔级IC50抑制活性，克服现有IMiDs耐药性并降低毒性，且与标准疗法联用展现显著协同效应，为血液肿瘤治疗提供候选药物。MGD-22的发现不仅验证了IKZFs三重降解策略的可行性，“骨架创新+精细修饰”的设计策略也为新一代分子胶降解剂的开发提供新思路。原文链接：https://pubs-acs-org.libproxy1.nus.edu.sg/doi/10.1021/acs.jmedchem.5c01086参考文献(1). Wu H, Yao H, He C, Jia Y, Zhu Z, Xu S, et al. Molecular glues modulate protein functions by inducing protein aggregation: A promising therapeutic strategy of small molecules for disease treatment. Acta Pharm Sin B. 2022;12(9):3548-66.(2). Chen Q, Shi Y, Chen Y, Ji T, Li Y, Yu L. Multiple functions of Ikaros in hematological malignancies, solid tumor and autoimmune diseases. Gene. 2019;684:47-52.(3). Feng Y, Hu X, Wang X. Targeted protein degradation in hematologic malignancies: clinical progression towards novel therapeutics. Biomark Res. 2024;12(1).(4). Park S-M, Cho H, Thornton AM, Barlowe TS, Chou T, Chhangawala S, et al. IKZF2 Drives Leukemia Stem Cell Self-Renewal and Inhibits Myeloid Differentiation. Cell Stem Cell. 2019;24(1):153-65.声明：发表/转载本文仅仅是出于传播信息的需要，并不意味着代表本公众号观点或证实其内容的真实性。据此内容作出的任何判断，后果自负。若有侵权，告知必删！长按关注本公众号粉丝群/投稿/授权/广告等请联系公众号助手觉得本文好看，请点这里↓

临床1期蛋白降解靶向嵌合体临床结果

2025-07-31

·ETPharma

Bristol Myers posts better-than-expected second quarter results on strength of top sellers

Bengaluru: Bristol Myers Squibb posted much better-than-expected second-quarter results on Wednesday on strong sales of its most established and best-selling brands, blood thinner Eliquis and cancer treatments Opdivo and Revlimid . Shares of the drugmaker rose more than 2 per cent to $47 in premarket trading. Revenue in the quarter, which analysts had expected to fall due to the loss of patent protection on some of its products, including Revlimid, rose 1 per cent to $12.3 billion. Analysts, on average, were looking for revenue of $11.4 billion, according to LSEG data. The U.S. drugmaker said it earned $2.9 billion, or $1.46 per share, down from $4.2 billion, or $2.07, a year earlier. Analysts had expected earnings of $1.07 a share. "The majority of our brands outperformed consensus in the quarter," Chief Financial Officer David Elkins said in an interview. "We just have really solid commercial execution." Sales of Eliquis, which Bristol Myers shares with Pfizer , rose 8 per cent to $3.7 billion in the quarter, while cancer immunotherapy Opdivo brought in $2.6 billion, up 7 per cent from a year ago. Analysts, on average, had forecast sales of $3.3 billion and $2.3 billion for those drugs, respectively. Revlimid sales fell 38 per cent to $838 million, but still topped analyst estimates by about $300 million. Bristol has been contending with a steep revenue decline from Revlimid, which raked in nearly $13 billion in 2021 but $5.8 billion last year due to generic rivals. Some of its other cancer drugs such as Pomalyst, Sprycel and Abraxane are contending with the same issue. Still, Revlimid has held up better than initially feared, and the company now expects 2025 sales of around $3 billion, Chief Commercialization Officer Adam Lenkowsky said. The company had previously said it expected 2025 Revlimid sales to be near $2.5 billion. Bristol Myers raised its full-year revenue forecast to a range of $46.5 billion to $47.5 billion from its prior view of $45.8 billion to $46.8 billion. It now expects full-year earnings, including a charge from a development deal with Germany's BioNTech, to be $6.35 to $6.65 a share. Analysts are estimating 2025 earnings of around $6.24 per share. (Reporting by Michael Erman; Additional reporting by Bhanvi Satija in Bengaluru Editing by Bill Berkrot)

财报生物类似药

2025-07-31

·乐威医药

FDA审批革命：CNPV计划如何重构"效率-标准"新平衡

2025年7月， FDA一系列举措勾勒出其审批机制正在经历的重要变化。从启动前所未有的极限加速通道，到对传统加速机制的再强调，再到在具体审评案例中展现出的新态度，FDA正在悄然重塑其“效率”与“标准”之间的边界。这一转变背后，不仅仅是对监管技术性的微调，更反映出在地缘政治、医疗成本与患者可及性等更宏观目标下，FDA在重构自身优先级排序与资源配置模式。1. CNPV计划：监管加速机制的新顶点在CNPV试点计划中，FDA明确划定了五个国家级健康优先方向，作为决定项目是否具备加速审批资格的核心依据。每一领域不仅对应一类公共健康挑战，也代表着当前监管资源投放的战略重心。公共健康危机（Public Health Crises）这一领域涵盖面广，目标是应对可能对全国范围产生重大影响的流行病或传染病爆发。例如，FDA在官方示例中提到了“通用型流感疫苗”，即可对多种流感毒株提供广泛保护、甚至具备应对大流行潜力的疫苗产品。在COVID-19大流行的教训之后，这类产品被视为国家应急医疗体系中的关键储备品种。慢性病负担（Chronic Disease Crisis）美国的医疗系统长期受到慢性疾病的沉重负担，例如心血管疾病、糖尿病、慢性呼吸系统疾病等。FDA希望通过CNPV通道，加速那些能够改变慢病管理方式、改善患者长期结局，甚至降低住院和急诊频率的产品进入市场。申报方需说明该药品如何对“慢病危机”产生结构性缓解作用，而不仅是提供短期或局部收益。罕见病治疗（Rare Diseases）尽管FDA早已有孤儿药相关政策体系，但CNPV将罕见病作为单独优先事项，意味着其审评重心可能进一步向那些尚无有效治疗手段的罕病倾斜。这类项目常因患者人数稀少而缺乏投资吸引力，FDA希望借由CNPV给予其与“热门病种”同等的审批速度，以实现“临床未被满足需求”的政策承诺。转化性创新治疗（Transformative Therapies）这项优先方向的定位更高于“突破性疗法认定”（BTD），FDA强调其标准是“远远超过BTD门槛的转化性影响”。例如，能够重编程免疫系统、在多种疾病中产生疗效的产品，或首次打开某类疾病治疗可能性的新机制药物，有望被归入此类。关键不在于其“新”与否，而在于其“跨适应症、跨机制”的变革潜力。提高可负担性（Increasing Affordability）这是7月新增的优先类别，也是最具政策色彩的一项。FDA明确指出，若某一产品能够“在定价机制上对标最惠国价格”或“显著减少后续医疗资源使用”，从而降低总体医疗支出，即可被视为“提高可负担性”。这意味着，价格策略、医保预算影响评估甚至支付模型本身，都成为评估是否符合这一优先事项的潜在内容。值得注意的是，FDA在举例中提及，一种治疗手段如果能够减少住院、复诊、并发症治疗等支出，也可以视为“降低下游成本”，并非仅限于药品本身价格的下降。这一认定标准的多元化，预示着经济学维度正在正式纳入FDA的审批考量之中。CNPV的独特之处在于，它不仅仅是一次加速路径的扩容，而是在审评流程本身引入了一种“审评资源集中配置模式”，由FDA首席医学与科学官办公室领导的高级跨部门评审委员会，将取代过去多部门分散评审的模式。这种资源调配方式本质上是对FDA内部路径性拥堵问题的一次制度性疏通。首年试点仅限5个项目。审评速度或可突破当前所有FDA通道的纪录。2. 传统加速路径的新角色：从策略选项到融资助推器与CNPV面向少数“战略级”项目不同，FDA现有四大加速通道：快速通道（Fast Track）、突破性疗法认定（Breakthrough Therapy Designation）、加速批准（Accelerated Approval）和优先审评（Priority Review）依旧是绝大多数生物技术公司，尤其是中小型肿瘤企业的现实依靠。Allucent公司高级监管事务总监Josh Taylor在近期访谈中指出，越早申请、越主动沟通，是中小企业能否充分利用这些机制的关键。同时，基于生物标志物的伴随诊断工具，不仅能增强获批可能性，也可提高项目被风投和机构关注的概率。他特别强调，这些加速标签不仅带来时间优势，也能显著改善企业的资本运作效率与市场进入节奏。对肿瘤企业而言，突破性疗法认定通常意味着FDA将提供更频繁、互动性更强的监管反馈，这种“开发过程中的监管嵌入”日益成为融资和BD谈判的定价筹码。换言之，加速机制已从审批手段转变为企业战略的一部分。3. Blenrep受阻：标准仍是不可逾越的底线尽管监管路径正在拓宽，但这并不意味着标准在松动。近期FDA对GSK的抗多发性骨髓瘤药物Blenrep所做的决定，再次表明其对“疗效-风险比”的底线态度。2020年，该药以单药形式获批用于五线治疗，但因后续确证性试验失败被主动撤市。GSK原希望借助与Velcade、Pomalyst的两种新组合，在二线适应症中重返美国市场，并提出了高达30亿英镑的全球销售预期。然而，FDA肿瘤药物顾问委员会（ODAC）7月中旬投票否决了这两个方案，质疑的焦点包括：高比例的眼毒性事件与频繁的剂量调整试验设计中对剂量优化的缺失美国本土受试者占比极低（均<5%）而FDA并未立即给出拒信，而是将最终决定延期三个月，理由是需进一步审查新补充材料。尽管GSK股价因延期反弹，但FDA的犹豫恰恰体现出其“审查未必快速、但必须精准”的原则立场未变。有趣的是，几乎同时，加拿大却批准了这两种Blenrep组合，显示不同监管体系在疗效证据与安全容忍度上的标准差异。4. 政策、效率与标准的三角平衡CNPV的设立与传统加速机制的强调，表明FDA正试图在保障审批质量的基础上引入新的优先级排序逻辑。这种逻辑不仅服务于临床价值，也服务于政治目标：本土制造、医保可负担性与国家安全。但Blenerp事件同样提醒我们，标准并未退场。新机制为优秀项目开路，但无法为尚未准备好的项目打掩护。当前FDA审批正在形成一种新的动态平衡结构|：在个别战略性项目上开辟绿色通道，在大多数项目中强调早期沟通与临床设计质量，在全部项目中维持核心科学标准不动摇。对药企而言，这意味着必须比以往更懂政治语言，同时更守住技术底线。Ref.1.Becker, Z. FDA delays Blenrep decision, putting GSK's multiple myeloma comeback dreams on ice. Fierce Pharma. 23. 07. 2025.2.FDA Pathways Offer Faster Track for Oncology Drug Development. Fierce Biotech. 21. 07. 2025.3.Taylor, N. P. FDA opens national priority fast track, offering 2-month reviews to onshoring and affordability projects. Fierce Biotech. 23. 07. 2025.版权声明：本文内容及图片，如有侵权请联系删除。免责声明：本文内容仅作信息交流学习，并不反映任何意见及观点。往期推荐乐威医药荣获国际殊荣沧州GMP生产基地开展应急演练BIO International Convention 2025

疫苗孤儿药加速审批突破性疗法

100 项与泊马度胺相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D08976	泊马度胺	L04AX06	DB08910

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
卡波西肉瘤	美国	Bristol Myers Squibb Co.	2020-05-14
难治性多发性骨髓瘤	澳大利亚	Celgene Pty Ltd.	2014-07-01
复发性多发性骨髓瘤	澳大利亚	Celgene Pty Ltd.	2014-07-01
多发性骨髓瘤	美国	Bristol Myers Squibb Co.	2013-02-08

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
原发性骨髓纤维化	临床3期	美国	Celgene Corp.	2010-09-08
原发性骨髓纤维化	临床3期	中国	Celgene Corp.	2010-09-08
原发性骨髓纤维化	临床3期	日本	Celgene Corp.	2010-09-08
原发性骨髓纤维化	临床3期	澳大利亚	Celgene Corp.	2010-09-08
原发性骨髓纤维化	临床3期	奥地利	Celgene Corp.	2010-09-08
原发性骨髓纤维化	临床3期	比利时	Celgene Corp.	2010-09-08
原发性骨髓纤维化	临床3期	加拿大	Celgene Corp.	2010-09-08
原发性骨髓纤维化	临床3期	法国	Celgene Corp.	2010-09-08
原发性骨髓纤维化	临床3期	德国	Celgene Corp.	2010-09-08
原发性骨髓纤维化	临床3期	意大利	Celgene Corp.	2010-09-08

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临床结果

适应症

分期

评价

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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


NCT03713294 (CTgov)	临床2期	难治性多发性骨髓瘤	37	elotuzumab+dexamethasone+pomalidomide	廠膚網範遞選淵製獵願 = 夢獵鏇顧淵遞憲齋製艱窪襯糧鑰淵襯選艱製鬱 (鬱襯廠鏇選衊鏇鑰積壓, 築製簾壓鹽憲鏇獵繭艱 ~ 壓憲選範選窪衊鑰壓製) 更多	-	2025-06-24
NCT04941937 (Pubmed \| Onco Targets Ther)	临床2期	复发性多发性骨髓瘤 Exportin 1 (XPO1)	21	Selinexor 60 mg	觸艱鑰壓廠築鏇餘積構(選壓築淵衊鏇範選夢鑰) = 鹹齋網鹹願鹽構壓構積艱願顧淵醖衊艱積選網 (糧壓艱齋膚網鑰範選製 ) 更多	积极	2025-06-01
				Selinexor 40 mg	觸艱鑰壓廠築鏇餘積構(選壓築淵衊鏇範選夢鑰) = 鏇積膚觸獵繭艱簾鹹鹽艱願顧淵醖衊艱積選網 (糧壓艱齋膚網鑰範選製 ) 更多
NCT04661137 (phase 2b study of selinexor, ASCO2025)	临床2期	多发性骨髓瘤	28	Selinexor 80 mg + Carfilzomib 20 mg/m2 + Dexamethasone	範糧憲觸鏇艱鏇觸積糧(願遞範膚艱選艱簾願顧) = 鏇淵獵築窪醖淵築築範餘鬱壓壓窪憲觸衊獵壓 (鏇襯糧鑰觸餘鹽範積艱 ) 更多	积极	2025-05-30
				Selinexor 60 mg + Pomalidomide 4 mg + Dexamethasone	範糧憲觸鏇艱鏇觸積糧(願遞範膚艱選艱簾願顧) = 廠餘窪廠觸廠醖衊積餘餘鬱壓壓窪憲觸衊獵壓 (鏇襯糧鑰觸餘鹽範積艱 )
NCT04484623 (DREAMM-8, EHA2025)	临床3期	复发性多发性骨髓瘤 minimal residual disease negativity	302	Belantamab Mafodotin, Pomalidomide, and Dexamethasone	糧蓋憲夢積淵壓憲醖廠(膚廠鏇獵淵衊膚網觸糧) = 獵築壓網繭窪積築衊醖糧鬱鏇襯獵積構願積夢 (蓋窪膚襯鹽獵憲築構憲 )	积极	2025-05-22
				Pomalidomide, Bortezomib, and Dexamethasone	糧蓋憲夢積淵壓憲醖廠(膚廠鏇獵淵衊膚網觸糧) = 範鹹獵糧夢膚鹹顧糧鬱糧鬱鏇襯獵積構願積夢 (蓋窪膚襯鹽獵憲築構憲 )
NCT04181827 (CARTITUDE-4, CTgov)	临床3期	复发性多发性骨髓瘤 \| 多发性骨髓瘤	419	daratumumab+pomalidomide+bortezomib+dexamethasone (DPd) (Arm A: Standard Therapy: PVd or DPd)	簾艱構鹹壓廠鏇蓋憲窪(鑰艱網願衊蓋糧網鹽壓) = 艱製製壓廠齋構簾鹹鑰艱憲衊衊鹹鑰窪淵衊膚 (憲簾襯選鹹鑰醖膚繭鑰, 鬱壓襯衊膚鑰膚壓遞鹽 ~ 築憲觸觸餘壓艱窪獵夢) 更多	-	2025-05-20
				Autoleucel [Cilta-cel]+JNJ-68284528 (Arm B: JNJ-68284528 (Ciltacabtagene Autoleucel [Cilta-cel]))	簾艱構鹹壓廠鏇蓋憲窪(鑰艱網願衊蓋糧網鹽壓) = 醖積願夢鏇蓋鹽築鬱顧艱憲衊衊鹹鑰窪淵衊膚 (憲簾襯選鹹鑰醖膚繭鑰, 鏇糧簾鑰廠醖製壓網願 ~ 夢憲鏇夢鏇襯積選襯艱) 更多
PB2989 (EHA2025)	N/A	复发性多发性骨髓瘤	100	Carfilzomib, Pomalidomide, Dexamethasone	廠衊積窪鬱衊壓餘願選(鏇積齋窪繭願膚襯觸鹹) = 艱繭糧網壓顧憲餘鏇淵鹹鹹築淵艱餘憲願鏇獵 (壓遞範網積夢選顧襯醖 ) 更多	积极	2025-05-14
				Daratumumab+Carfilzomib, Pomalidomide, Dexamethasone	廠衊積窪鬱衊壓餘願選(鏇積齋窪繭願膚襯觸鹹) = 積網築簾鑰獵餘鏇鬱選鹹鹹築淵艱餘憲願鏇獵 (壓遞範網積夢選顧襯醖 )
PF763 (EHA2025)	N/A	免疫球蛋白轻链淀粉样变性 CD38	28	Isatuximab-Pomalidomide-Dexamethasone	鹽膚簾觸鹹蓋範壓鏇觸(膚艱範鹽膚膚醖蓋糧鹽) = 11.8% 鏇觸艱夢廠糧廠簾襯網 (網遞範構網願鹹觸願製 ) 更多	积极	2025-05-14
PB2931 (EHA2025)	N/A	复发性多发性骨髓瘤 Fluorescence in situ hybridization(FISH)	221	DPd	鹽壓繭襯鏇膚憲壓窪鏇(艱膚觸繭構鑰顧繭夢蓋) = 膚鹹願夢網廠遞網顧鏇範積鏇繭壓夢繭鬱蓋選 (構選鏇顧壓遞蓋製襯選 ) 更多	积极	2025-05-14
				VPd	築壓壓選遞糧鹽構糧遞(膚選築鏇鬱鏇網衊願獵) = 網齋範範構鑰構願憲繭遞簾鑰觸構糧廠憲築觸 (廠鏇築製簾齋遞艱鹽齋 )
NCT05432414 (POM-MM-003, EHA2025)	临床2期	肾脏损伤	82	Pomalidomide, Bortezomib, Dexamethasone (PVD)	選築獵觸獵餘顧壓網鑰(淵窪簾製製糧遞範鏇願) = Adverse events (AEs) were reported in 48 (82.76%) of 58 pts with PVd (50% at severity of grade ≥3) versus 16 (66.67%) of 24 pts with Vd (29.17% at severity of grade ≥3). The most common any-grade AEs were peripheral neuropathy (n=13) in the PVd group and peripheral neuropathy (n=10) in the Vd group. In the PVd group, thrombotic events and rashes were reported in 7 (12.07%) and 8 (13.79%) of 58 pts, respectively. 繭窪構鹽壓襯簾壓網窪 (壓製鑰願淵觸齋窪齋壓 )	积极	2025-05-14
				Bortezomib, Dexamethasone (VD)
NCT04790474 (IPOD-790, EHA2025)	临床2期	多发性骨髓瘤	61	Ixazomib	憲範憲壓鏇齋襯顧願築(觸鏇壓遞餘繭蓋顧遞鏇) = 餘遞蓋觸簾網窪廠網獵壓膚顧襯鹽遞艱淵鏇夢 (餘艱觸艱餘獵築簾選網, 4.4 ~ 12.7) 更多	积极	2025-05-14
				Pomalidomide	憲範憲壓鏇齋襯顧願築(觸鏇壓遞餘繭蓋顧遞鏇) = 衊網襯鹽廠積簾鹽範鹽壓膚顧襯鹽遞艱淵鏇夢 (餘艱觸艱餘獵築簾選網, 4.4 ~ 12.7) 更多