This phase II trial tests how well ziftomenib works in treating patients with NPM1 mutated or KMT2A rearranged acute myeloid leukemia (AML) and are not eligible to receive standard therapy. AML is often due to genetic changes in the cancer cells, including mutations in the NPM1 gene and rearrangements involving the KMT2A gene. These mutations result in activation of the menin pathway. Menin is a type of protein in the body that helps to regulate some of the naturally occurring processes in the body, but can also be involved in some types of cancers. Ziftomenib blocks this menin pathway and may prevent the cancer cells from continuing to grow. Giving ziftomenib may kill more cancer cells in patients with NPM1 mutated or KMT2A rearranged AML that are not eligible to receive standard therapy.

开始日期2025-06-01

申办/合作机构

Ohio State University Comprehensive Cancer Center

[+1]

NCT06871410

/ Not yet recruiting临床1期IIT

CD83 CAR T in Relapsed or Refractory Acute Myeloid Leukemia (AML): A Phase I Trial

This phase I trial tests the safety, side effects, and best dose of genetically engineered cells (CD83 chimeric antigen receptor [CAR] T cells) in treating patients with acute myeloid leukemia (AML) that has come back after a period of improvement (relapsed) or has not responded to previous treatment (refractory). CD83 is a protein that is found on AML blasts. Blasts are abnormal immature white blood cells that can multiply uncontrollably: filling up the bone marrow and preventing the production of other cells important for survival. CD83 CAR T cells represent a new cell therapy to eliminate AML blasts, while avoiding the risk for graft versus host disease (GVHD) after stem cell transplant to replace bone marrow or, tumor toxicity like myeloid aplasia where the body's own immune system causes damage to the bone marrow stem cells. Therefore, human CD83 CAR T cells are a promising cell-based approach to preventing two critical complications of stem-cell transplant - GVHD and relapse. Giving CD83 CAR T cells may be safe, tolerable, and/or effective in treating patients with relapsed or refractory AML.

开始日期2025-04-01

申办/合作机构

Roswell Park Comprehensive Cancer Center

NCT06923111

/ Not yet recruitingN/A

A Comparative Observational Study to Evaluate the Safety and Effectiveness of Xromi (Hydroxycarbamide Oral Solution 100mg/ml) for the Prevention of Vaso-occlusive Complications of Sickle Cell Disease in Children Under 2 Years of Age.

This post-authorisation safety and efficacy study (PRECISE PASS) evaluates the use of Xromi® (hydroxycarbamide 100 mg/mL oral solution) in children aged 9 months to under 2 years with sickle cell disease (SCD).
The objective is to assess the safety profile and clinical effectiveness of Xromi® under routine clinical conditions. The study includes a prospective cohort of Xromi®-treated patients and a matched retrospective comparator cohort of untreated patients. Participants will be followed for 24 months from treatment initiation or matched index date.

开始日期2025-04-01

申办/合作机构

Nova Laboratories Ltd.

[+1]

100 项与羟基脲相关的临床结果

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100 项与羟基脲相关的转化医学

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100 项与羟基脲相关的专利（医药）

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14,660

项与羟基脲相关的文献（医药）

2025-12-01·Blood Research

Efficacy and safety of thalidomide with hydroxyurea in sickle cell anemia: a quasi-experimental clinical trial

Article

作者: Paul, Anindita ; Samal, Priyanka ; Bishoyi, Ajit Kumar ; Bahirat, Harshwardhan ; Epari, Venkatarao

Abstract:

Background:

The clinical course of sickle cell anemia (SCA) is variable, with chronic hemolysis and end-organ damage caused by microvascular occlusion. We evaluated the efficacy and safety of thalidomide plus hydroxyurea (HU) compared with HU alone to determine whether the combination provides a superior clinical benefit and safety profile.

Methods:

This was an open-label quasi-experimental clinical trial (Clinical Trials Registry of India, CTRI Registration Number 2023/04/065682). Patients with SCA aged > 12 years and postmenopausal females aged > 45 years were allocated 1:1 to receive either HU (20 mg/kg/day) and thalidomide (50 mg/day) in Group A or HU (20 mg/kg/day) only in Group B.

Results:

The frequency of vaso-occlusive crises (VOCs), transfusion requirements, variations in hematological parameters (hemoglobin [Hb], fetal hemoglobin [HbF], and sickle hemoglobin [HbS]), and side effects between the groups were assessed over 12 months. Repeated-measures analysis of variance was used to determine changes across the observation period. The mean age of the 66 patients diagnosed with SCA (homozygous HbS mutation) was 32.9 (standard deviation ± 11.5) years, and 57.6% were males. Over the 12-month observation period, Group A had significantly fewer VOCs (3.48 ± 2.81) and packed red blood cell transfusions (3.61 ± 2.19) than Group B (11.36 ± 4.20 VOCs; 13.27 ± 3.70 transfusions) (p = 0.0001). There was a significant increase in Hb (8.2 ± 1.8 to 11.8 ± 1.2 g/dL), a decrease in HbS% (72.5 ± 5.5 to 64.5 ± 5.4), and a rise in HbF% (18.9 ± 5.1 to 28.4 ± 5.6) (p < 0.0001) in Group A.

Conclusion:

Combining thalidomide with HU significantly reduced VOCs and transfusion requirements, improved Hb and HbF%, and decreased HbS levels.

2025-05-01·JOURNAL OF MOLECULAR GRAPHICS & MODELLING

A DFT study of pure and Si-decorated boron nitride allotrope Irida monolayer as an effective sensor for hydroxyurea drug

Article

作者: Sur, Dharmesh ; Ray, Subhashree ; Ridha-Salman, Hayder ; Krithiga, T ; Ballal, Suhas ; Mohammed, Mohammed Hashim ; Hsu, Chou-Yi ; Singh, Abhayveer ; Almehizia, Abdulrahman A

Investigating effective nanomaterials for the detection of hydroxyurea anticancer drugs is essential for promoting human health and safeguarding environmental integrity. This research utilized first-principles estimations for examining the adhesion and electronic characteristics of hydroxyurea (HU) on both pristine and Si-decorated innovative two-dimensional boron nitride allotrope, known as Irida analogous (Ir-BNNS). Analyzing the adsorption energy revealed that the HU molecule has a significant interaction (E_ad = -1.27 eV) with the Si@Ir-BNNS, whereas it has weak interaction P-Ir-BN. Moreover, the analysis of the electron density distributions was conducted to investigate the microcosmic interaction mechanism between HU and Ir-BNNS. The Si@Ir-BNNS was highly sensitive to HU due to the observable alterations in the electrical conductance and magnetism. At ambient temperature, the Si@Ir-BNNS had a recovery time of 5.96 ms towards HU molecules. The DFT estimations can be conducive to exploring the applications of Si@Ir-BNNS in effectively sensing HU.

2025-05-01·CURRENT OPINION IN HEMATOLOGY

Gene therapy for sickle cell disease and thalassemia

Review

作者: Panzieri, Daniele Lello ; Scaramellini, Natalia ; Cappellini, Maria Domenica

Purpose of review:

Thalassemia and sickle cell disease are among the most frequent monogenic hereditary diseases. Access to transfusions, iron chelation therapies and drugs such as hydroxyurea have improved life expectancy and quality of life. However, these diseases still cause significant disability. The first available curative therapy, bone marrow transplantation, is unfortunately not feasible for all patients. Over the past decade, numerous studies have focused on finding new curative therapies, and many clinical trials have evaluated different gene therapy approaches.

Recent findings:

The therapeutic targets focus on adding functional copies of the gene encoding β-globin in defective CD34+ cells, mainly using lentiviral vectors directed towards HSCs. More recently, the focus has shifted to inducing fetal hemoglobin production at therapeutic levels or repairing the underlying molecular defect, using novel gene editing techniques involving CRISPR-Cas9, transcription activation-like effector protein nucleases, zinc finger nucleases and base editing. Preclinical and clinical studies now focus on optimizing how gene therapy is performed and delivered to reduce or eliminate myeloablative treatment and its potential adverse events.

Summary:

In this review, we explore the potential to induce fetal hemoglobin production at therapeutic levels or to repair the underlying molecular defect that causes the disease genetically. Here, we review recent gene editing studies that are opening a new era in curative treatment for hemoglobinopathies.

239

项与羟基脲相关的新闻（医药）

2025-04-15

·PRNewswire

Norgine strengthens rare disease portfolio with acquisition of Theravia

Acquisition of Theravia from Mérieux Equity Partners represents meaningful step forward in Norgine's strategy for sustainable growth, adding a complementary portfolio of rare disease medicines Transaction further establishes Norgine's position as a partner of choice for commercialising rare and specialty pharmaceuticals in Europe PARIS, April 15, 2025 /PRNewswire/ -- Norgine and Theravia announced today that they have entered into a definitive agreement under which Norgine will acquire Theravia, an international pharmaceutical company specialising in cutting-edge treatments for patients with rare and debilitating conditions. Recent deals with Fennec Pharma for PEDMARQSI® and X4 Pharma for mavorixafor demonstrate Norgine's strong emphasis on driving growth in rare disease and specialty medicines through acquisitions and in-licensing. Theravia's innovations have resulted in successful launches of life-saving medications which have changed patient outcomes worldwide. Theravia has several products in the rare disease space, including SIKLOS®, for adults and children with sickle cell disease, and ORPHACOL®, a medicine for adults and children who have a genetic disorder that affects bile production by the liver. These products span both the rare haematology and rare hepatology therapeutic areas and are complementary to Norgine's existing rare and specialty portfolio. The development of Theravia in the past few years has been supported by its majority shareholder Mérieux Equity Partners, a healthcare dedicated investment firm based in France. "This acquisition is a unique opportunity for Norgine to bolster our growth trajectory, as well as our rare disease portfolio." said Janneke van der Kamp, Chief Executive Officer, Norgine. "With our strong legacy and proven track record of successfully bringing innovative treatments to patients, we believe we are well placed to ensure the Theravia medicines reach their full potential." Franck Hamalian, Chief Executive Officer, Theravia, added: "The joining of our companies brings together the skills, know-how and geographical presence that will create a European-based champion of rare and ultra rare disease. Our combined product portfolios and Norgine's legacy and experience will enable broader access to medicines for patients with high unmet medical needs." With the acquisition of Theravia, Norgine will now have six core products in its rare disease portfolio (PEDMARQSI®, eflornithine, mavorixafor, AGILUS®, SIKLOS® and ORPHACOL®) thereby comprising a franchise of critical scale with the ability to be a key growth driver in the medium-to-long-term. Norgine looks forward to building on this transaction as we continue to strengthen our platform for future acquisitions and in-licensing opportunities to drive growth. The transaction remains subject to obtaining customary regulatory approvals from the competent authorities. Notes About Theravia Theravia is an international pharmaceutical laboratory specializing in rare or neglected diseases. Formed through the merger of Addmedica and CTRS, Theravia is dedicated to addressing the unmet medical needs of patients with these challenging conditions. About SIKLOS® SIKLOS® is used in adults, adolescents and children over two years of age who have sickle-cell syndrome, a genetic disease where the red blood cells become rigid and sticky and change from being disc-shaped to being crescent-shaped (like a sickle). It is used to prevent recurrent, painful vaso-occlusive crises that happen when blood vessels become blocked by the abnormal red blood cells, restricting the flow of blood to an organ. They can include acute chest syndrome, a life-threatening condition when the patient has sudden chest pain, fever, hard breathing or signs of fluid in the lungs on an X-ray. SIKLOS® is marketed in 17 countries around the world. About ORPHACOL® ORPHACOL® is a medicine containing cholic acid, a substance found in the bile, which is used to digest fats. It is approved in the US and Europe used to treat adults and children from one month of age who have a genetic abnormality that makes them unable to produce bile. The therapy is used in patients who do not have enough of two specific liver enzymes which makes their liver unable to produce enough of the main components of bile, called primary bile acids, such as cholic acid. When these primary bile acids are lacking, the body produces abnormal bile acids instead which can damage the liver, potentially leading to life-threatening liver failure. ORPHACOL® is marketed in 23 countries around the world. About PEDMARQSI® PEDMARQSI® is a novel formulation of anhydrous sodium thiosulfate, specifically developed and manufactured for the prevention of cisplatin-induced hearing loss in patients 1 month to <18 years of age. It is the first and only preventative treatment developed for cisplatin-induced ototoxicity to support children and adolescent patients with localised, non-metastatic solid tumour cancers. It was granted marketing authorisation by the EMA in May 2023 (under the paediatric-use marketing authorisation (PUMA) programme) and the MHRA in October 2023. About Mavorixafor Mavorixafor is a selective CXCR4 receptor antagonist approved in the U.S. and marketed by X4 as XOLREMDI®, an oral, once-daily treatment for patients 12 years of age and older with WHIM syndrome, a rare primary immunodeficiency. In January 2025, X4 submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for mavorixafor for the treatment of WHIM syndrome, for which it has been granted Orphan Drug Designation by both the EMA and the U.S. Food and Drug Administration. X4 is also developing the medicine to treat chronic neutropenia (CN) and is currently conducting a global, pivotal Phase 3 clinical trial in certain CN disorders. Norgine has responsibility for commercialisation in Europe, Australia, and New Zealand following regulatory approvals. About Eflornithine Eflornithine has been investigated for use as a post maintenance treatment for high-risk neuroblastoma (HRNB) in paediatric patients with no active disease (NAD) / no evidence of disease (NED) after first line multiagent, multimodality therapy. It is a targeted therapy that blocks an enzyme called ornithine decarboxylase (ODC), responsible for producing polyamines, which are important to tumour growth and development. The medicine is approved by the FDA for a maintenance therapy for high-risk neuroblastoma in adult and pediatric patients. In April 2024, an application for approval was submitted by Norgine for the use of eflornithine in high-risk neuroblastoma (HRNB), via Project Orbis in Australia, Switzerland and the United Kingdom. In January 2025, a marketing authorisation application was filed to the European Medicines Agency (EMA) for the medicine in high-risk neuroblastoma (HRNB). About AGILUS® AGILUS® is a medicine used to treat malignant hyperthermia (rapid rise in body temperature caused by uncontrolled muscle contractions) in adults and children. Malignant hyperthermia is a serious reaction to certain medicines used for general anaesthesia during surgery or other medical procedures. AGILUS® is approved for use by the EMA for for the treatment of malignant hyperthermia in adults and children in combination with adequate support measures. About Mérieux Equity Partners Founded in 2009, Mérieux Equity Partners ("MxEP") is a leading European healthcare-specialized investment firm, with two dedicated platforms, Venture Capital and Buyout, supporting companies ranging from start-ups to established leaders. Benefiting from a longstanding expertise and a large network, MxEP invests in companies with ambitious growth projects and transformative products or services in healthcare. MxEP is AMF-accredited and currently manages c.€1.5bn of AuM. About Norgine Norgine is a uniquely positioned, specialty pharmaceutical and consumer healthcare company, with over €550 million of annual revenues and a 120-year track record of bringing life-changing products to patients and consumers across our core markets of Western Europe, Australia and New Zealand. Norgine's integrated approach – strong commercial capabilities, as well as deep medical, regulatory and clinical expertise, in-house manufacturing, robust supply networks, and best-in-class enabling functions – ensures that Norgine can deliver high-quality, transformative medicines quickly and effectively to over 25 million patients annually. Norgine is a nimble, innovative, and high-performing company that has been transformed by a relentless focus on operational excellence. This focus will enable us to secure the legacy of more than a century of innovation and doing the right thing by our patients, as we push the boundaries and take strides into therapeutic innovation. NORGINE and the sail logo are trademarks of the Norgine group of companies. Logo - WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

上市批准并购孤儿药临床3期

2025-04-12

·小药说药

银屑病药物研发管线与市场全景

-01-引言：银屑病治疗需求的迫切性银屑病是一种由遗传、免疫及环境因素共同诱发的慢性自身免疫性皮肤病，影响全球2-3%的人口。它与角质形成细胞增殖异常有关，临床特征为红斑、界限清晰的丘疹和圆形斑块。大约75%的银屑病患者至少有一种合并症，其中银屑病关节炎最为常见。银屑病病程长、易复发、合并症多（如心血管疾病、关节炎等），对患者生活质量造成严重损害。银屑病是环境和遗传因素之间复杂相互作用的结果，涉及先天和适应性免疫系统的异常反应，导致皮肤损伤。在过去的15年中，研究已经表明TH17/ IL-17通路在银屑病的发病机制中起着主要作用，而炎症介质如IL-17、IL-23和肿瘤坏死因子（TNF）是治疗的关键靶点。尽管传统疗法（如糖皮质激素、光疗）长期占据主导，但近年来生物制剂和口服靶向药的突破正重塑治疗格局。-02-一、已获批的疗法银屑病的治疗取决于疾病的类型、部位和程度。大多数局限性斑块型银屑病可以用局部糖皮质激素治疗，然而长期使用可能会因疗效丧失和皮肤萎缩而变得复杂。钙三烯（一种维生素D类似物）和他扎罗汀（一种视黄酸衍生物）也能有效治疗局限性银屑病。紫外线是许多广泛银屑病患者的有效治疗方法，但它可能会增加皮肤癌症的发病率，应谨慎应用于免疫功能低下的患者。各种全身性药物可用于严重、广泛的银屑病。如甲氨蝶呤，尤其是对银屑病关节炎患者；有时也会使用其他免疫抑制剂，包括羟基脲、6-硫鸟嘌呤、硫唑嘌呤和环孢菌素。阿曲汀是一种口服类视黄醇，也可用于治疗严重的银屑病，但其受到致畸性的限制。阿普雷司特是一种口服磷酸二酯酶4（PDE4）抑制剂，已被批准用于银屑病和银屑病关节炎。在过去的二十年里，靶向促炎细胞因子的多种生物制剂由于其强大的疗效和可接受的耐受性，已成为中重度斑块型银屑病的重要治疗选择。从2004年起，首批获批的生物药是抑制TNF的单克隆抗体，包括依那西普、英夫利昔单抗和阿达木单抗。自那以后，抑制TH17/IL-17途径的单克隆抗体也加入了市场，从2009年开始使用ustekinumab，一种IL-12和IL-23的抑制剂，靶向包括TH17/IL-18途径在内的多种TH细胞途径。靶向IL-17家族成员或其受体的几种单克隆抗体也已获得批准，包括secukinumab、ixekizumab和brodalumab，以及靶向IL-23的单克隆抗体，包括risankizumab、tildrakizumab和guselkumab。-03- 二、新兴疗法Deurefacitinib是酪氨酸激酶2（TYK2）的口服选择性抑制剂，分别于2022年和2023年被美国食品药品监督管理局（FDA）和欧盟批准用于治疗成人中重度斑块型银屑病。Deurefacitinib介导参与银屑病发病机制细胞因子的信号传导，这是唯一一种被批准的选择性靶向JAK激酶家族成员TYK2的疗法。JAK抑制剂也被批准用于其他免疫炎症性疾病，但有严重不良事件有关，FDA在所有JAK抑制剂的标签上都有黑框警告。而Deurefacitinib的作用机制与其他JAK抑制剂不同，因为它与变构位点而非ATP结合位点结合，其对TYK2的选择性可能会限制其副作用。因此，目前FDA在其标签中没有加入黑框警告。在支持批准deurefacitinib的III期临床试验（POETYK PSORIASIS-1和POETYK-PSORIASIS-2）中，58%和53%的患者在第16周的银屑病面积和严重程度指数评分（PASI75）改善了75%或75%以上，而安慰剂组的改善率为13%和9%，而接受apremilast对照组的患者治疗改善率分别为35%和40%。此外，在第16周时，36%和27%的Deurefacitinib给药患者达到PASI90，而在接受apremilast治疗的患者中，这一比例分别为20%和18%。Deurefacitinib也显示出长期疗效，82%的患者在第24周达到PASI75，并维持到第52周。武田正在开发另一种TYK2抑制剂TAK-279，用于治疗银屑病。TAK-279的IIb期临床试验的阳性结果于2022年11月公布。在第12周，与安慰剂（6%）相比，接受TAK-279的患者中有更大比例达到PASI75，5 mg、15 mg和30 mg剂量组分别为44%、68%和67%。第三阶段研究已于2023年10月开始。另一方面，Ventyx Biosciences基于II期试验结果停止了用于治疗银屑病的TYK2抑制剂VTX958的开发。在II期试验中，其达到了主要疗效终点，但疗效的大小没有达到期望的目标。Bimekizumab（Bimzelx；UCB Pharma）是一种抑制TH17/IL-17通路的单克隆抗体，于2022年在欧盟和英国被批准用于治疗银屑病，2023年在美国被批准用于银屑病。与其他IL-17靶向单克隆抗体不同，Bimekizumab同时抑制IL-17A和IL-17F。另一种正在开发中的抑制TH17/IL-17途径的潜在疗法是口服小分子IL-17抑制剂DC-806。2022年，DICE Therapeutics公布了DC-806治疗银屑病的I期试验的阳性数据，报告称高剂量组在4周时PASI比基线平均减少44%，而安慰剂组为13%。DICE于2023年被礼来公司以24亿美元收购，DC-806目前处于II期研究中。DC-853是一种口服的下一代化合物，与DC-806相比，其效力和代谢稳定性有所提高，目前处于I期研究中。Union Therapeutics正在开发一种新一代高效PDE4抑制剂Orismilast。在一项IIa期研究中，与安慰剂相比，使用Orismilast治疗在第16周可显著改善PASI评分。此外，在健康受试者中，Orismilast的改良释放制剂显示出相似的药代动力学特性和较少的胃肠道副作用，后续开发将基于改良释放制剂。2023年报告的IIb期结果显示，40-49%的患者在第16周达到PASI75，而接受安慰剂治疗的患者为17%。没有发现新的安全信号，证实了PDE4抑制剂的良好安全性。另一种治疗银屑病的PDE4抑制剂是ME3183，它正在由Meiji Pharma开发。2023年8月，ME3183在二期试验中达到PASI75的主要终点。该疗法显示早期PASI改善，并显示出良好的耐受性。JNJ-2113是一种IL-23受体的肽抑制剂，口服给药。在FRONTIER 1的 IIb期试验中达到了主要终点，37–79%接受不同剂量的JNJ-2113的患者在第16周达到PASI75，而接受安慰剂的患者为9%。最后，用于治疗斑块型银屑病的口服TYK2/JAK1抑制剂TLL018-205（HighlightLL Pharma）的II期试验正在进行中。-04-三、银屑病药物的市场分析在截至2023年6月的12个月内，全球银屑病药物市场价值约340亿美元，约占免疫疾病总市场的30%。美国仍然是银屑病疗法的主导国家市场，约占总销售额的78%、，在过去五年中，它以约18%的复合年增长率增长。IL-23抑制剂risankizumab和guselkumab以约31%的市场份额主导美国银屑病市场，其次是IL-17抑制剂ixekizumab和secukinumab，约占23%l；TNF抑制剂占23%，ustekinumab占13%。Deurefacitinib是美国银屑病市场的最新进入者，根据BMS的数据，2023年第三季度，deucreacitinib在美国的销售额为6200万美元。自2022年9月批准以来，该疗法的接受率一直很低，主要是由于来源和报销有限；然而，随着人们对口服药物治疗越来越感兴趣，这种情况预计在未来几年会发生变化。目前，全球银屑病市场的前景看起来很有希望，预计2023年至2030年的复合年增长率为8-10%。这一增长将主要由人口老龄化、几种新的口服疗法的引入以及政府提高银屑病防治意识举措的扩大推动。按照目前的增长速度，预计到2030年市场规模将达到580亿至670亿美元。然而，随着阿达木单抗的生物仿制药进入美国市场，新疗法将受到越来越多生物仿制药的挑战。其他领先的生物制剂，包括ustekinumab、ixekizumab和secukinumab，将在不久的将来失去美国市场的排他性，也将面临生物仿制药的竞争。-05-结语银屑病治疗市场的增长与挑战正成为全球医药行业关注的焦点。从市场规模来看，人口老龄化是核心驱动力之一。人口老龄化明显地推动了银屑病市场的增长，这一趋势推动全球银屑病市场规模从2022年的265亿美元攀升至2030年的600亿-670亿美元。新型靶向药物彻底改变了治疗格局。以IL-12/23、IL-17等为靶点的生物制剂因精准抑制炎症通路，副作用更少，市场份额快速提升。口服JAK抑制剂和小分子药物的兴起也丰富了治疗选择。尽管前景乐观，行业仍面临多重挑战：研发成本攀升、专利悬崖集中到来，以及新兴市场支付能力不足。未来，组合疗法开发、真实世界证据应用，以及AI驱动的药物发现平台，或将成为企业建立竞争壁垒的关键。参考资料：1. The pipeline and market for psoriasis drugs. Nat Rev Drug Discov. 2024 Jan 31公众号内回复“ADC”或扫描下方图片中的二维码免费下载《抗体偶联药物：从基础到临床》的PDF格式电子书！公众号已建立“小药说药专业交流群”微信行业交流群以及读者交流群，扫描下方小编二维码加入，入行业群请主动告知姓名、工作单位和职务。

基因疗法免疫疗法临床研究

2025-03-03

·PipelineReview

Protagonist and Takeda Announce Positive Topline Results from Phase 3 VERIFY Study of Rusfertide in Patients with Polycythemia Vera

− Study met the primary endpoint, with a significantly higher proportion of clinical responders on rusfertide compared to placebo − All four key secondary endpoints were met, including EU primary endpoint and patient-reported outcomes − Rusfertide was generally well tolerated; no new safety findings were observed in the study NEWARK, CA, USA & OSAKA, Japan & CAMBRIDGE, MA, USA I March 03, 2025 I Protagonist Therapeutics, Inc. (“Protagonist”) ( NASDAQ:PTGX ) and Takeda ( TSE:4502/NYSE:TAK ) today announced positive topline results for the Phase 3 VERIFY study, in which phlebotomy-dependent patients with polycythemia vera (PV) were randomized to treatment with either rusfertide or placebo, as an add-on to standard of care treatment. The study met its primary endpoint and all four key secondary endpoints. Rusfertide is a first-in-class investigational hepcidin mimetic peptide therapeutic, which has received Orphan Drug designation and Fast Track designation from the U.S. Food & Drug Administration (FDA). Key findings from the study include: “The positive results of the Phase 3 VERIFY study across the primary and all key secondary endpoints provide compelling evidence of the potential for rusfertide as a first-in-class erythrocytosis-specific agent to address unmet medical needs in patients with PV who are unable to achieve adequate hematocrit control despite standard of care treatments,” said Arturo Molina, M.D., M.S., Chief Medical Officer of Protagonist. “We plan to submit additional details of these promising results for presentation at upcoming medical conferences in 2025. We are immensely grateful to the patients, study staff and principal investigators who made the VERIFY study possible.” Patients with PV are at increased risk for life-threatening cardiovascular and thrombotic events. Many patients with PV require regular phlebotomy, a process of removing blood to manage elevated hematocrit levels caused by an excess of red blood cells, as well as treatment with cytoreductive therapies. Phlebotomy can be burdensome and exacerbate symptoms, including severe fatigue, visual disturbances and iron deficiency, which impact patients’ quality of life. The reduction of hematocrit below 45% is a primary treatment goal for patients with PV as recommended by current treatment guidelines. “We are encouraged by these results and excited about the potential of rusfertide to help patients living with PV. These patients may experience a high treatment burden, and severe symptoms can impact their quality of life,” said Andy Plump, M.D., Ph.D., President of R&D at Takeda. “We are deeply committed to bringing additional treatment options to those living with blood cancers, including myeloid cancers such as PV.” “The totality of impressive clinical data to date shows that rusfertide has the potential for meaningful positive impact on the lives of patients with PV,” said Dinesh V. Patel, Ph.D., President and Chief Executive Officer at Protagonist. “We look forward to working with our partner, Takeda, to submit our findings to the regulatory agencies. Today’s study results also mark a critical inflection point in Protagonist’s decade long journey in the hepcidin program and further validates our platform and expertise in innovating highly differentiated peptide-based medicines to fulfill unmet medical needs.” Under the license and collaboration agreement between Protagonist and Takeda, Protagonist earns a $25 million milestone payment following these positive results. The milestone is payable following completion of the VERIFY clinical study report. The impact on Takeda’s financial results for the fiscal year ending March 31, 2025 (FY2024), following the study results, is immaterial. Protagonist will host a conference call and webcast, for which details can be found below. Protagonist Investor Conference Call and Webcast Details The dial-in numbers for Protagonist’s investor update on Monday, March 3rd at 8:30 am ET are: US-based Investors: 1-877-300-8521 International Investors: 1-412-317-6026 Conference Call ID: 1793905 The webcast link for the event can be found here: https://viavid.webcasts.com/starthere.jsp?ei=1708360&tp_key=94f2832555 A replay of the presentation will be available on the Protagonist Investor Relations Events and Presentations webpage following the event. About VERIFY The Phase 3 VERIFY trial (NCT05210790) is an ongoing, three-part, global, randomized, placebo-controlled trial evaluating rusfertide in 293 patients with polycythemia vera over a 156-week period. The trial is evaluating the efficacy and safety of once-weekly, subcutaneously self-administered rusfertide in patients with uncontrolled hematocrit who are phlebotomy dependent despite standard of care treatment, which could include hydroxyurea, interferon and/or ruxolitinib. The primary endpoint of the study was the proportion of patients achieving a response during weeks 20-32, which was defined as the absence of “phlebotomy eligibility.” To meet phlebotomy eligibility, patients in the study were required to have: confirmed hematocrit ≥45% that was ≥3% higher than their baseline hematocrit value, or hematocrit ≥48%. All patients have completed their participation in the randomized, placebo-controlled portion of the trial evaluating the efficacy and safety of rusfertide plus current treatment versus placebo plus current treatment and are now in the open-label portions of the trial. About Protagonist Protagonist Therapeutics is a discovery through late-stage development biopharmaceutical company. Two novel peptides derived from Protagonist’s proprietary discovery platform are currently in advanced Phase 3 clinical development, with New Drug Application submissions to the FDA expected in 2025. Icotrokinra (formerly, JNJ-2113) is a first-in-class investigational targeted oral peptide that selectively blocks the Interleukin-23 receptor (“IL-23R”) which is licensed to JNJ Innovative Medicines (“JNJ”), formerly Janssen Biotech, Inc. Following icotrokinra’s joint discovery by Protagonist and JNJ scientists pursuant to the companies’ IL-23R collaboration, Protagonist was primarily responsible for development of icotrokinra through Phase 1, with JNJ assuming responsibility for development in Phase 2 and beyond. Rusfertide, a mimetic of the natural hormone hepcidin, is currently in Phase 3 development for the rare blood disorder polycythemia vera (PV). Rusfertide is being co-developed and will be co-commercialized with Takeda Pharmaceuticals pursuant to a worldwide collaboration and license agreement entered into in 2024 under which the Company remains primarily responsible for development through NDA filing. The Company also has a number of pre-clinical stage oral drug discovery programs addressing clinically and commercially validated targets, including IL-17 oral peptide antagonist PN-881, oral hepcidin program, and oral obesity program. More information on Protagonist, its pipeline drug candidates and clinical studies can be found on the Company’s website at www.protagonist-inc.com . About Takeda Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit www.takeda.com . 1 A responder is a patient who completed weeks 0-32 of the study, was not phlebotomy eligible and did not receive a phlebotomy during weeks 20-32. To meet phlebotomy eligibility, patients in the study were required to have: confirmed hematocrit ≥45% that was ≥3% higher than their baseline hematocrit value, or hematocrit ≥48%. See “About VERIFY” section. 2 Proportion of patients with hematocrit less than 45%. 3 Mean change from baseline to week 32 using PROMIS Fatigue SF-8a, a questionnaire that measures patient-reported fatigue symptoms and their impact on daily life. 4 Mean change from baseline to week 32 using MFSAF TSS-7 v. 4.0, a questionnaire that measures patient reporting of seven key symptoms related to myelofibrosis (many of which are common among PV patients as well). SOURCE: Takeda Pharmaceutical Co

临床3期临床结果引进/卖出快速通道孤儿药

100 项与羟基脲相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00341	羟基脲	L01XX05	DB01005

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
真性红细胞增多症	日本	Clinigen KK	2013-03-25
真性红细胞增多症	日本	Bristol-Myers Squibb KK	2013-03-25
血管闭塞危机	欧盟	Theravia Pharma SAS	2007-06-29
血管闭塞危机	冰岛	Theravia Pharma SAS	2007-06-29
血管闭塞危机	列支敦士登	Theravia Pharma SAS	2007-06-29
血管闭塞危机	挪威	Theravia Pharma SAS	2007-06-29
难治性慢性粒细胞白血病	日本	Clinigen KK	1992-07-03
原发性血小板增多症	日本	Clinigen KK	1992-07-03
头颈部肿瘤	中国	国药控股股份有限公司	1981-01-01
肾肿瘤	中国	国药控股股份有限公司	1981-01-01
黑色素瘤	中国	国药控股股份有限公司	1981-01-01
费城染色体阳性慢性粒细胞白血病	中国	国药控股股份有限公司	1981-01-01
头颈部鳞状细胞癌	中国	国药控股股份有限公司	1981-01-01
镰状细胞血症	美国	CHEPLAPHARM Arzneimittel GmbH	1967-12-07
疼痛	美国	CHEPLAPHARM Arzneimittel GmbH	1967-12-07

未上市

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适应症	最高研发状态	国家/地区	公司	日期
白蛋白尿	临床2期	科特迪瓦	Theravia Pharma SAS	2019-05-28
白蛋白尿	临床2期	法国	Theravia Pharma SAS	2019-05-28
白蛋白尿	临床2期	瓜德罗普	Theravia Pharma SAS	2019-05-28
白蛋白尿	临床2期	马里	Theravia Pharma SAS	2019-05-28
白蛋白尿	临床2期	马提尼克	Theravia Pharma SAS	2019-05-28
白蛋白尿	临床2期	塞内加尔	Theravia Pharma SAS	2019-05-28
β地中海贫血	临床2期	牙买加	Nova Laboratories Ltd.	2019-01-03
β地中海贫血	临床2期	英国	Nova Laboratories Ltd.	2019-01-03
血红蛋白SC疾病	临床2期	牙买加	Nova Laboratories Ltd.	2019-01-03
血红蛋白SC疾病	临床2期	英国	Nova Laboratories Ltd.	2019-01-03

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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


ASH2024	N/A	镰状细胞血症	-	Hydroxyurea (American children with SCA)	構衊鹹簾簾齋艱壓選網(淵廠糧廠構鹽淵淵襯鏇) = 窪繭鑰簾獵蓋糧製襯餘淵壓選蓋齋膚餘淵艱憲 (鏇蓋憲鹽簾鑰夢糧獵鹽 ) 更多	-	2024-12-08
				Hydroxyurea (African children with SCA)	構衊鹹簾簾齋艱壓選網(淵廠糧廠構鹽淵淵襯鏇) = 遞願鑰築鹽齋願膚範窪淵壓選蓋齋膚餘淵艱憲 (鏇蓋憲鹽簾鑰夢糧獵鹽 ) 更多
ASH2024	N/A	镰状细胞血症	-	Hydroxyurea therapy	顧窪鹽憲夢顧範鬱艱餘(積醖築襯鹽繭壓觸製壓) = 壓鹽鹽鹹鏇範糧憲顧餘鹽醖簾廠簾蓋衊構艱鹹 (糧襯蓋齋選憲顧築築衊 ) 更多	-	2024-12-08
ASH2024	N/A	镰状细胞血症	-	Hydroxyurea	鹽憲膚鏇鏇膚鑰選齋製(觸積窪鏇齋憲範選築衊) = 壓鑰壓製窪築憲積鹽築醖餘淵齋遞構鹹製淵鹹 (夢艱艱淵艱顧鏇夢膚蓋 ) 更多	-	2024-12-08
				Hydroxyurea (Control group)	鹽憲膚鏇鏇膚鑰選齋製(觸積窪鏇齋憲範選築衊) = 憲鹹網齋鹽簾繭繭憲範醖餘淵齋遞構鹹製淵鹹 (夢艱艱淵艱顧鏇夢膚蓋 ) 更多
ASH2024	N/A	镰状细胞血症	-	Hydroxyurea	壓獵鑰廠壓願築鑰製繭(鏇餘顧製艱壓構願選製) = 願繭繭蓋鏇願積齋網憲顧齋醖憲積糧壓鹽觸糧 (構鑰艱範網衊遞壓觸製 )	-	2024-12-08
				No Hydroxyurea	-
ASH2024	N/A	镰状细胞血症	-	Hydroxyurea	醖選鹹選鬱淵壓艱廠憲(蓋醖膚憲積襯壓襯壓簾) = forgetting to take medication (56.9%), cost (40.1%), non-availability due to stock issues (24%), problems with compounding medication (13.8%), medication fatigue (12%), feeling of wellness (12%), side effects (2.4%), and doubts about efficacy (1.2%) 鹹繭顧構壓製網顧繭壓 (觸鬱壓遞觸醖齋壓淵艱 ) 更多	-	2024-12-08
NCT01966731 (REACH, ASH2024)	临床1/2期	镰状细胞血症	606	Hydroxyurea at MTD	鬱齋艱餘襯膚鏇鑰艱醖(顧顧顧選憲遞鬱衊築簾) = Two children contracted transfusion-acquired HIV, both of whom have continued hydroxyurea at MTD while concurrently receiving highly active antiretroviral treatment. 襯積鏇壓積網膚醖鏇齋 (鑰範鹽簾鹹積醖廠築鑰 ) 更多	积极	2024-12-08
				Fixed-Dose Hydroxyurea
ASH2024	N/A	镰状细胞血症	-	Hydroxyurea (Observation Arm)	糧積鬱壓壓鬱願壓壓遞(鹽膚餘衊觸窪齋淵顧簾) = 夢繭願獵糧遞繭遞繭積廠選壓鹹製鏇網齋醖鹹 (顧選醖憲鏇鬱醖淵願鏇 ) 更多	-	2024-12-07
				PK-guided hydroxyurea treatment	範鬱鹹選觸願願網衊鏇(簾膚壓夢鑰醖選獵憲選) = 鏇鹽範膚顧觸醖鬱膚淵製獵鹽觸鹽憲網獵壓獵 (顧遞壓廠範鹽鹽鏇鏇觸, 8.8) 更多
NCT03763656 (HUPK, CTgov)	临床1/2期	β地中海贫血 \| 血红蛋白SC疾病	33	Hydroxyurea	獵淵鬱夢鹹齋艱夢鏇夢(構淵壓蓋繭膚顧襯鬱製) = 壓鑰齋遞醖憲鏇觸憲範膚鬱夢繭鹽齋遞艱築簾 (餘糧蓋簾獵餘遞夢範廠, 夢鹹廠夢簾夢鬱網積憲 ~ 壓蓋醖積餘積鹹淵構襯) 更多	-	2024-10-28
NCT05005182 (CTgov)	临床2期	骨髓增生异常/骨髓增生性疾病 \| 血小板增多症 \| 骨髓增生异常综合征	3	Bone Marrow Biopsy+Luspatercept	簾齋獵網製齋積鏇積廠 = 積願鑰獵願餘獵廠遞膚選醖鏇繭糧獵鹽齋糧網 (壓顧積願鹹糧壓選鹹廠, 膚製簾蓋構鏇糧糧鏇簾 ~ 蓋窪觸醖艱鑰顧壓醖艱) 更多	-	2024-09-19
ATS2024	N/A	间质性肺疾病	-	Hydroxyurea	鏇簾憲衊選簾窪憲憲繭(獵鑰範積鹽簾獵夢艱網) = If not diagnosed, Hydroxyurea-induced interstitial pneumonitis may lead to Acute respiratory failure and lung fibrosis. 積顧憲壓艱遞鏇齋憲鏇 (獵夢壓憲願壓齋選觸憲 ) 更多	-	2024-05-19