Hydroxycarbamide

NEWARK, CA, USA & OSAKA, Japan & CAMBRIDGE, MA, USA I June 01, 2025 I Protagonist Therapeutics, Inc. (“Protagonist”) ( NASDAQ:PTGX ) and Takeda ( TSE:4502/NYSE:TAK ) announced detailed results from the Phase 3, randomized, placebo-controlled VERIFY study evaluating rusfertide in patients with polycythemia vera (PV), which met the primary and all key secondary endpoints. The data will be presented as a late-breaking oral presentation at the 61 st American Society of Clinical Oncology (ASCO) Annual Meeting Plenary Session (LBA3) at 2:09 pm CDT today. PV is characterized by overproduction of red blood cells (erythrocytosis), which may increase blood viscosity, or thickness, potentially resulting in life threatening thrombotic events such as stroke, deep vein thrombosis and pulmonary embolism. People with PV can experience burdensome symptoms, including severe fatigue, difficulty in concentrating, night sweats and pruritus, which may negatively impact their daily functioning and quality of life. Hematocrit is the ratio of red blood cells to total amount of blood in the body. Achieving and maintaining controlled hematocrit levels of <45% is the primary treatment goal in PV to prevent thrombotic events and alleviate symptoms, but many patients still experience uncontrolled hematocrit levels with current standard of care treatments. Rusfertide, an investigational, first-in-class hepcidin mimetic peptide therapeutic, is under evaluation in the Phase 3 VERIFY study for its potential to regulate iron homeostasis and red blood cell production to control hematocrit levels in patients with PV. In the study, patients dependent on frequent phlebotomy, with or without treatment with cytoreductive therapy, were randomized to receive once-weekly rusfertide or placebo, as an add-on to current standard of care treatment. “PV poses significant challenges for patients, including debilitating symptoms and the risk of serious thrombotic events, and hematocrit control is crucial to improving patient outcomes. The VERIFY study demonstrated that treatment with rusfertide controls hematocrit levels in phlebotomy-dependent patients, including patients receiving cytoreductive therapies,” said Dr. Andrew T. Kuykendall, M.D., VERIFY Lead Investigator and Associate Member in the Department of Hematology at Moffitt Cancer Center. “These results suggest rusfertide has the potential to become part of the standard of care treatment for patients with PV.” The study met its primary endpoint, which was the proportion of patients achieving a clinical response, defined as the absence of phlebotomy eligibility during study Weeks 20-32. Study results demonstrated 76.9% of patients treated with rusfertide plus current standard of care achieved a clinical response, compared to 32.9% in the placebo plus current standard of care group (p<0.0001). 1 The response observed in the rusfertide arm was consistent across subgroups, regardless of risk status or type of concurrent cytoreductive therapy. 1 In addition, all key secondary endpoints met statistical significance in favor of the rusfertide arm compared to the placebo arm in the VERIFY study, as follows: Rusfertide was generally well tolerated. The majority of adverse events were low grade and non-serious and no serious adverse events considered related to rusfertide were reported. There was no evidence of increased risk of cancer in patients treated with rusfertide plus current standard of care compared to patients treated with placebo plus current standard of care at the time of the primary analysis. Cancer events were reported in one patient in the rusfertide arm (0.7%) and in seven patients in the placebo arm (4.8%). The most common treatment-emergent adverse events were localized injection site reactions (55.9%), anemia (15.9%) and fatigue (15.2%). 1 “These findings underscore rusfertide’s potential as a first-in-class erythrocytosis-specific treatment for PV and validate more than a decade of scientific innovation originating from Protagonist’s peptide technology platform,” said Dinesh V. Patel, Ph.D., President and Chief Executive Officer at Protagonist. “We would like to thank all the patients, study staff and investigators for participating in the VERIFY study. We are pleased to partner with Takeda as we continue to advance rusfertide to potentially transform the standard of care in PV patients around the world.” “These promising pivotal data strongly support rusfertide’s potential benefit for a broad spectrum of patients with PV who may be receiving current standard of care therapies but not achieving adequate hematocrit control,” said Phuong Khanh (P.K.) Morrow, M.D., Head of the Oncology Therapeutic Area Unit (OTAU) at Takeda. “We look forward to receiving additional data from the VERIFY trial later this year, advancing rusfertide towards regulatory approval and continuing our collaboration with Protagonist to bring this innovative therapy to patients.” Rusfertide has received Orphan Drug designation and Fast Track designation from the U.S. Food & Drug Administration (FDA). Takeda Investor Conference Call and Webcast Details Takeda will host an investor call regarding this update on Sunday, June 1, 6-6:45 pm CDT/ 7-7:45 pm EDT / Monday, June 2, 08:00-08:45 (JST). The call will be held using the Zoom platform and Zoom simultaneous interpretation function. Kindly pre-register from the below link: https://zoom.us/webinar/register/WN_rNp8tpIiRsemQRawBCDRMA#/registration An on-demand replay will be made available on Takeda’s website after the conclusion of the event. Protagonist Investor Conference Call and Webcast Details The dial-in numbers for Protagonist’s investor update on Monday, June 2nd at 5:00-6:00 am PDT/ 8:00-9:00 am EDT are: The webcast link for the event can be found here: https://viavid.webcasts.com/starthere.jsp?ei=1718556&tp_key=360d3b714d 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 study (NCT05210790) is an ongoing, three-part, global, randomized, placebo-controlled study evaluating rusfertide in 293 patients with polycythemia vera over a 156-week period. The study is evaluating the efficacy and safety of once-weekly, subcutaneously self-administered rusfertide in patients with uncontrolled hematocrit who are phlebotomy-dependent despite current 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 study evaluating the efficacy and safety of rusfertide plus current standard of care versus placebo plus current standard of care and are now in the open-label portions of the study. 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, an oral hepcidin program, and an 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 . SOURCE: Takeda Pharmaceutical Co

小李，28岁，因腹胀加重半年就诊。最初他以为是吃得多导致的“发胖”，尝试节食后腹部却越发突出，同时伴有疲乏无力、反复腹泻。他的面色苍白，皮肤略显蜡黄。多次外院检查均未发现明确原因，被建议“调整饮食，多锻炼”。最终，小李到当地三甲医院血液科就诊。查体发现，他的脾脏显著肿大，触及肋缘以下6厘米，且胸骨轻叩有压痛。血液检测提示白细胞、血小板显著减少，骨髓穿刺显示肥大细胞显著增多。进一步基因检测发现KIT D816V突变，最终确诊为一种由肥大细胞异常增殖引起的罕见疾病：系统性肥大增多症（SM）。什么是SM？肥大细胞增多症是异常肥大细胞在一个或多个组织器官中浸润导致的一种罕见的异质性肿瘤。根据第五版世界卫生组织（WHO）分类标准，肥大细胞增多症可分为三个疾病亚型——皮肤型肥大细胞增多症（CM）、系统性肥大增多症（SM）和肥大细胞肉瘤（MCS）。系统性肥大增多症（SM）是侵袭性肥大细胞在真皮组织以外的一个或多个组织、器官或系统的克隆性增殖，并释放大量的血管活性介质，引起多器官功能障碍，常见的受累部位包括骨髓、皮肤、脾脏、淋巴结、肝脏和（或）单核-巨噬细胞系统，约占肥大细胞增多症的10%。临床表现包括全身症状、肥大细胞活化症状（介质导致的症状）、相关疾病症状以及体征：（1）全身症状：发热、疲劳、体重减轻、盗汗等。（2）肥大细胞活化症状：①过敏反应；②乏力；③眩晕、晕厥/昏迷；④皮肤：面部、颈部和胸部皮肤潮红，瘙痒伴或不伴皮疹，荨麻疹伴或不伴血管性水肿；⑤胃肠：胃部不适、腹泻、恶心、呕吐、腹痛、腹胀、胃食管反流病；⑥神经精神：头痛、脑雾、认知障碍、焦虑、抑郁、记忆力减退、注意力不集中；⑦心血管：心率快、胸痛、低血压、高血压、血压不稳定；⑧呼吸：喘息和气短；⑨骨骼肌肉：骨骼肌肉疼痛、骨质硬化、骨质减少、骨质疏松；⑩鼻喉：鼻痒、鼻塞、喉咙发痒和肿胀。（3）相关疾病症状：部分患者存在血液系统疾病相关症状。（4）体征：肝肿大、脾肿大和淋巴结肿大等。分型SM可分为骨髓肥大细胞增多症（BMM）、ISM、冒烟型系统性肥大细胞增多症（SSM）、ASM、SM-AHN和MCL六个亚型。诊断SM需满足主要标准和1项次要标准或同时满足≥3项次要标准。治疗系统性肥大增多症（SM）的治疗以缓解肥大细胞活化症状、降低疾病负担为目标，具体措施包括以下几方面：1.抗介质治疗： 避免诱因，局部应用润肤霜或色甘酸钠，严重症状时使用抗组胺药、抗白三烯药物或皮质类固醇激素。2.预防性治疗： 针对慢性介质相关症状可逐步应用酮替芬、H1和H2受体阻断药、白三烯受体拮抗剂及质子泵抑制剂等。严重患者可能需要奥马珠单抗或糖皮质激素。3.急性过敏反应的处理： 系统性荨麻疹或过敏性休克需立即肌注肾上腺素，并根据情况重复注射，必要时静脉给药。4.骨质疏松治疗： 可根据骨病严重程度使用双膦酸盐或其他骨代谢相关药物。5.传统治疗： 羟基脲和干扰素-α可用于控制症状和减少肥大细胞负担，克拉屈滨对严重病例疗效显著。6.靶向治疗： 小分子激酶抑制剂（如阿伐替尼、米哚妥林）通过抑制KIT突变改善病情，特别适用于晚期SM患者。异基因造血干细胞移植：对于进展型SM（AdvSM）患者，allo-HSCT是唯一潜在的治愈手段，但需严格评估适应症。参考资料：1.  中华医学会血液学分会实验诊断学组，中国肥大细胞增多症协作网络. 成人系统性肥大细胞增多症诊断与治疗中国指南（2022年版）. 中华血液学杂志，2022，43(12):969-978. DOI:10.3760/cma.j.issn.0253-2727.2022.12.0012.罗睿恒，王二华，李昕,等. 急性髓系白血病合并系统性肥大细胞增多症1例. 中国临床案例成果数据库，2022，04(01):E07211-E07211. DOI:10.3760/cma.j.cmcr.2022.e07211来源 | 梅斯医学编辑 | wanny神经系统罕见病交流群↓点击下方“阅读原文”，下载梅斯医学APP吧！