Pegfilgrastim (Amgen)

In the news release, FDA Approves FILKRI™ (filgrastim-laha), Accord BioPharma's Biosimilar to NEUPOGEN® (filgrastim), issued 17-Feb-2026 by Accord BioPharma over PR Newswire, we are advised by the company that changes have been made. The complete, corrected release follows, with additional details at the end: FDA Approves FILKRI™ (filgrastim-laha), Accord BioPharma’s Biosimilar to NEUPOGEN® (filgrastim) FILKRI completes Accord BioPharma's comprehensive granulocyte colony-stimulating factor (G-CSF) portfolio alongside UDENYCA ® (pegfilgrastim-cbqv ) RALEIGH, N.C. , Feb. 17, 2026 /PRNewswire/ -- Accord BioPharma , the U.S. specialty division of Intas Pharmaceuticals, Ltd., focused on the development of oncology, immunology, and critical care therapies, announced that the U.S. Food and Drug Administration (FDA) has approved FILKRI™ (filgrastim-laha), a biosimilar to NEUPOGEN ® (filgrastim), for patients with cancer receiving myelosuppressive chemotherapy; patients with acute myeloid leukemia receiving induction or consolidation chemotherapy; patients with cancer undergoing bone marrow transplantation; patients with severe chronic neutropenia; and patients acutely exposed to myelosuppressive doses of radiation (hematopoietic syndrome of acute radiation syndrome). 1 The approval of FILKRI marks the sixth product in Accord BioPharma's growing portfolio of FDA-approved biosimilars, following the company's acquisition last year of UDENYCA ® (pegfilgrastim-cbqv), a biosimilar to Neulasta ® (pegfilgrastim), 2 as well as the seventh approved product in the overall portfolio. With the addition of FILKRI, Accord BioPharma now offers physicians in the U.S. a comprehensive granulocyte colony-stimulating factor (G-CSF) portfolio with both long-acting (UDENYCA) and short-acting (FILKRI) biosimilar options to meet the needs of patients, providers, and practices. 1,2 Accord has applied for and expects to receive a permanent Q-code from the U.S. Centers for Medicare & Medicaid Services (CMS), which will standardize and facilitate the billing and reimbursement process across hospital outpatient, ambulatory surgery center, and physician office settings of care. Tackling Vital Healthcare Needs Neutropenia is a common and potentially serious complication of cancer treatment and occurs when white blood cells called neutrophils—which serve as a major line of defense against bacterial and fungal infections—fall below normal levels. This reduction increases a person's risk of developing an infection. Granulocyte colony-stimulating factor, or G-CSF, is a growth factor that stimulates the production and release of neutrophils in the body. By accelerating neutrophil recovery, G-CSF can help reduce the duration of neutropenia. 3,4 FILKRI belongs to the G-CSF class and is a growth factor manufactured by recombinant DNA technology. FILKRI works by regulating the production of neutrophils within the bone marrow. 1 "Cancer patients often face significant challenges with treatment-related neutropenia, which can lead to serious infections, treatment delays, and dose reductions that may compromise therapeutic outcomes," said Chrys Kokino, President, Accord North America. "With FILKRI alongside UDENYCA, the provider-preferred option over Neulasta and all other biosimilars,* we now offer healthcare providers a complete G-CSF portfolio with short- and long-acting biosimilar options. This positions Accord BioPharma as a committed partner in oncology supportive care, expanding access to high-quality biologics." Demonstrated Biosimilarity and Safety Profile FILKRI was approved based on two randomized studies in healthy adults, with pharmacokinetics (PK)/pharmacodynamics (PD) assessed in one study and safety and immunogenicity evaluated in both, compared with reference product NEUPOGEN. These studies demonstrated the biosimilarity in PD and PK parameters between FILKRI and NEUPOGEN and showed overall safety and immunogenicity similar to NEUPOGEN. 5 FILKRI is contraindicated in patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors, such as filgrastim products or pegfilgrastim products. 1 Expanding Access: Accord BioPharma's Biosimilar Vision Accord BioPharma believes deeply in the power of biosimilars to reshape the future of treatment. With the support of Intas, an established global leader with nearly five decades of experience, Accord BioPharma is transforming the conventional treatment landscape across several priority therapeutic areas by introducing biosimilars to the U.S. market. As part of this commitment, Accord BioPharma is rapidly expanding its U.S. portfolio with a strategic goal to launch 20 biosimilar products by 2030, solidifying its position as a reliable partner delivering more affordable, high-quality biologic alternatives. In addition to developing and marketing their own biosimilar products, the company is strategically collaborating with select partners around the world to bring more biosimilars to the U.S. market as swiftly as possible. "This approval of FILKRI demonstrates our steadfast dedication to expanding access to cost-effective biologic treatments in the critically important field of oncology," said Binish Chudgar, Chairman and Managing Director of Intas Pharmaceuticals. "We're proud to have one of the largest biosimilar pipelines within the industry. With Accord BioPharma, we're positioning ourselves as a dependable partner in the United States—one that's deeply committed to understanding stakeholder priorities and revolutionizing patient access." Current Portfolio of Brands The company's current commercial portfolio includes the full UDENYCA franchise, including the UDENYCA prefilled syringe, autoinjector, and on-body injector, IMULDOSA ® (ustekinumab-srlf), a biosimilar to Stelara ® (ustekinumab), HERCESSI™ (trastuzumab-strf), a biosimilar to Herceptin ® (trastuzumab), and CAMCEVI ® (leuprolide) 42 mg injectable emulsion. 6,7 Please refer to the Important Safety Information and full Prescribing Information for these products, and to the Boxed Warning for HERCESSI. Accord BioPharma has received FDA approval on three additional products: CAMCEVI ® (leuprolide) ETM (every three months), OSVYRTI ® (denosumab-desu), a biosimilar to PROLIA ® (denosumab), and JUBEREQ ® (denosumab-desu), a biosimilar to XGEVA ® (denosumab). 8,9 The company plans to announce the commercial launch of these products later this year. Please refer to the Important Safety Information and full Prescribing Information for these products, and to the Boxed Warning for OSVYRTI. Contact: abipr@accordhealthcare.com IMPORTANT SAFETY INFORMATION FILKRI is contraindicated in patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors (G-CSFs) such as filgrastim or pegfilgrastim products. Splenic Rupture: Splenic rupture, including fatal cases, has been reported following the administration of filgrastim products. Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture. Acute Respiratory Distress Syndrome (ARDS): ARDS has been reported in patients receiving filgrastim products . Evaluate patients who develop fever and lung infiltrates or respiratory distress for ARDS . Discontinue FILKRI in patients with ARDS. Serious Allergic Reactions: Serious allergic reactions, including anaphylaxis, have been reported in patients receiving filgrastim products . The majority of reported events occurred upon initial exposure . Provide symptomatic treatment for allergic reactions. Allergic reactions, including anaphylaxis, in patients receiving filgrastim products can recur within days after the discontinuation of initial anti-allergic treatment . Permanently discontinue FILKRI in patients with serious allergic reactions. Sickle Cell Disorders: Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving filgrastim products . Discontinue FILKRI if sickle cell crisis occurs. Glomerulonephritis: Has occurred in patients receiving filgrastim products . Diagnoses were based on azotemia, hematuria, proteinuria, and renal biopsy . Generally, events resolved after dose reduction or discontinuation of filgrastim products . If causality is likely, consider dose-reduction or interruption of FILKRI. Alveolar Hemorrhage and Hemoptysis: Alveolar hemorrhage, manifesting as pulmonary infiltrates and hemoptysis requiring hospitalization, have been reported in FILKRI-treated healthy donors undergoing peripheral blood progenitor cell (PBPC) collection mobilization . Hemoptysis resolved with discontinuation of filgrastim products. The use of FILKRI for PBPC mobilization in healthy donors is not an approved indication. Capillary Leak Syndrome (CLS): CLS has been reported after G-CSF administration, including filgrastim products and is characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration. Episodes vary in frequency, severity, and may be life-threatening if treatment is delayed . Patients with symptoms should be closely monitored and receive appropriate treatment. Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML): Patients with Severe Chronic Neutropenia (SCN ): Confirm the diagnosis of SCN before initiating FILKRI therapy. MDS and AML have been reported to occur in the natural history of congenital neutropenia without cytokine therapy. Cytogenetic abnormalities, transformation to MDS, and AML have also been observed in patients treated with filgrastim products for SCN. Abnormal cytogenetics and MDS have been associated with the eventual development of myeloid leukemia. The effect of filgrastim products on the development of abnormal cytogenetics and the effect of continued filgrastim administration in patients with abnormal cytogenetics or MDS are unknown. Monitor patients for signs and symptoms of MDS/AML in these settings. If a patient with SCN develops abnormal cytogenetics or myelodysplasia‚ the risks and benefits of continuing FILKRI should be carefully considered. Patients with Breast and Lung Cancer : MDS and AML have been associated with the use of filgrastim products in conjunction with chemotherapy and/or radiotherapy in patients with breast and lung cancer. Monitor patients for signs and symptoms of MDS/AML in these settings. Thrombocytopenia: Thrombocytopenia has been reported in patients receiving filgrastim products. Monitor platelet counts. Leukocytosis: Patients with Cancer Receiving Myelosuppressive Chemotherapy : White blood cell counts ≥ 100,000/mm 2 were observed in about 2% of patients who received filgrastim products at dosages above 5 mcg/kg/day. Discontinue FILKRI if the absolute neutrophil count (ANC) surpasses 10,000/mm 2 after the chemotherapy-induced ANC nadir has occurred. Monitor CBCs at least twice weekly during therapy with FILKRI. Discontinuation of filgrastim therapy usually resulted in a 50% decrease in circulating neutrophils within 1 to 2 days‚ with a return to pretreatment levels in 1 to 7 days. Cutaneous Vasculitis: Moderate or severe cases of cutaneous vasculitis has been reported in patients treated with filgrastim products . Most reports involved patients with SCN receiving long-term filgrastim therapy . Hold FILKRI therapy in patients with cutaneous vasculitis . FILKRI dose may be reduced when the symptoms resolve and the ANC has decreased. Potential Effect on Malignant Cells: FILKRI is a growth factor that primarily stimulates neutrophils. The granulocyte colony-stimulating factor (G-CSF) receptor through which FILKRI acts has also been found on tumor cell lines. The possibility that FILKRI acts as a growth factor for any tumor type cannot be excluded. The safety of filgrastim products in chronic myeloid leukemia (CML) and myelodysplasia has not been established. Simultaneous Use with Chemotherapy and Radiation Not Recommended: The safety and efficacy of FILKRI given simultaneously with cytotoxic chemotherapy and radiation have not been established . Do not use FILKRI 24 hours before or after administration of cytotoxic chemotherapy . The safety and efficacy of FILKRI have not been evaluated in patients receiving concurrent radiation therapy . Avoid the simultaneous use of FILKRI with chemotherapy and radiation therapy. Nuclear Imaging: Increased hematopoietic activity of the bone marrow has been associated with transient positive bone-imaging changes on nuclear imaging. Aortitis: Aortitis has been reported in patients receiving filgrastim products . It may occur as early as the first week after start of therapy . Manifestations may include generalized signs and symptoms such as fever, abdominal pain, malaise, back pain, and increased inflammatory markers (e.g., c-reactive protein and white blood cell count) . Consider aortitis in patients who develop these signs and symptoms without known etiology. Discontinue FILKRI if aortitis is suspected. The most common adverse reactions in patients: with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs (≥ 5% difference in incidence compared to placebo) are pyrexia, pain, rash, cough, and dyspnea with AML (≥ 2% difference in incidence) are pain, epistaxis and rash with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by BMT (≥ 5% difference in incidence) is rash with severe chronic neutropenia (SCN) (≥ 5% difference in incidence) are pain, anemia, epistaxis, diarrhea, hypoesthesia and alopecia INDICATIONS FILKRI is a leukocyte growth factor indicated to: Decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever Reduce the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML) Reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g.‚ febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation (BMT) Reduce the incidence and duration of sequelae of severe neutropenia (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia Increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome) To report SUSPECTED ADVERSE REACTIONS, contact Accord BioPharma Inc at 1-866-941-7875 or FDA at 1-800-FDA-1088 or . FILKRI is supplied as single-dose prefilled syringes for subcutaneous or intravenous use in 300 mcg/0.5 mL and 480 mcg/0.8 mL strengths. For more information, please see the full Prescribing Information . About Accord BioPharma Accord BioPharma, Inc., the U.S. specialty division of Intas Pharmaceuticals, Ltd., seeks to provide affordable, accessible, patient-centric therapies in oncology, immunology, and critical care. With a focus on improving the patient experience, Accord BioPharma goes beyond the biology of medicine to see disease from the patients' perspective and develop high-quality therapies that impact patients' lives. Accord BioPharma believes in the ability of biosimilars to increase access and options for patients and deliver savings to the U.S. healthcare system, and is striving to offer one of the deepest biosimilar portfolios in the industry. For more information, visit AccordBioPharma.com . *Based on cumulative average of prescriptions written from September 2025 - January 2026, according to IQVIA drug distribution data. References: FILKRI ® (filgrastim-laha) injection. Prescribing Information. Accord BioPharma. UDENYCA ® (pegfilgrastim-cbqv). Prescribing Information. Accord BioPharma. Simpson, P. Clinical Implications and Future Research of Neutrophils in Health and Disease. Immunome Research 2024;20(3): 1-2. Link, H. Current state and future opportunities in granulocyte colony‑stimulating factor (G‑CSF). Supportive Care in Cancer 2022;30:7067–7077. Accord BioPharma. Data on file. IMULDOSA ® (ustekinumab-srlf). Prescribing Information. Accord BioPharma. HERCESSI™ (trastuzumab-strf). Prescribing Information. Accord BioPharma. OSVYRTI ® (denosumab-desu). Prescribing Information. Accord BioPharma. JUBEREQ ® (denosumab-desu). Prescribing Information. Accord BioPharma. All trademarks, logos, and brand names are the property of their respective owners. Correction:  An earlier version of this release had the incorrect link to the full Prescribing Information. View original content to download multimedia: SOURCE Accord BioPharma

序章 高墙后的死亡阴影 1985年，美国马里兰州，国立癌症研究所的病房里，气氛凝重。41岁的乳腺癌患者伊芙琳正经历第三轮强化化疗。治疗在缩小肿瘤，但每一次化疗后，她的血常规报告就像一场定时审判——白细胞计数，尤其是中性粒细胞，会无情地跌入谷底。 这一次，数字跌得特别深。她的口腔开始出现溃疡，体温悄然攀升至39.5°C。经验丰富的肿瘤护士立刻拉响了警报：“中性粒细胞减少性发热！” 伊芙琳被迅速转入隔离病房。尽管使用了最强效的广谱抗生素，但在几乎没有“卫兵”（中性粒细胞）的身体里，细菌肆虐无忌。五天后，她死于难以控制的败血症休克。 在她主治医生的笔记本上，沉重地记录着：“死因：急性骨髓抑制导致的中性粒细胞缺乏性脓毒症。根本原因：缺乏有效的骨髓造血功能恢复手段。” 这一幕，在1980年代全球的肿瘤病房里反复上演。化疗如同一把双刃剑，在斩杀癌细胞的同时，也重创了骨髓这一“血细胞工厂”。中性粒细胞减少性发热及其导致的感染死亡，是当时限制化疗剂量、阻碍治愈率提升的最主要障碍。肿瘤学家们深知，若能筑起一道保护白细胞的“高墙”，就能让化疗这把剑挥得更彻底、更安全。 彼时，谁也不会想到，这道“高墙”的基石，竟源于二十多年前一位科学家对小鼠骨髓细胞培养皿中几个微小“斑点”的痴迷。 1 骨髓中的“星图” ——集落刺激因子理论的诞生 时间倒转至1961年，澳大利亚墨尔本，沃尔特与伊丽莎·霍尔医学研究所。一位名叫唐纳德·梅特卡夫的年轻科学家，正在尝试一项看似简单却前所未有的实验：他从小鼠的骨髓中提取出原始的造血细胞，将它们放在特制的半固体培养基（如琼脂）中培养。当时的普遍认知是，这些细胞在体外很快就会死亡。 然而，几天后，当梅特卡夫在显微镜下观察时，他看到了令他终身难忘的景象：在原本均匀的培养基背景上，星星点点地散布着一些微小的、不规则的细胞团。他敏锐地意识到，每一个“斑点”，都可能是一个造血细胞的后代——一个“集落”。更关键的是，他发现，只有向培养基中添加某些特定的组织提取液或条件培养基时，这些集落才会出现。 梅特卡夫做出了一个划时代的推论：体内一定存在一些可溶性的物质，它们像“生长指令”或“刺激因子”一样，指挥着原始的造血干细胞向特定的血细胞谱系（红细胞、粒细胞、巨噬细胞等）增殖和分化。他将这些假想的物质命名为 “集落刺激因子”。 在接下来的近二十年里，梅特卡夫及其团队如同宇宙学家绘制星图一般，系统地鉴定和描述了不同类型的CSF。他们发现，有些因子主要刺激粒细胞和巨噬细胞的形成（GM-CSF），有些则更专一地驱动粒细胞（G-CSF）或巨噬细胞（M-CSF）的发育。其中，G-CSF因其对中性粒细胞——这道抗感染前线最核心的“步兵”——的特异性促生成作用，显得尤为重要。 然而，整个1970年代，CSF都只是生物学概念和实验室现象。它们以微乎其微的量存在于复杂的生物体液中，化学本质不明，更遑论提纯和应用。梅特卡夫被誉为“CSF之父”，但他的发现，距离拯救病房里的伊芙琳，还隔着巨大的技术鸿沟。 2 基因猎手 ——从“现象”到“分子”的惊险一跃 转机伴随着1980年代分子生物学革命的浪潮而来。此时，美国加州的安进公司还是一家名不见经传的小型生物技术初创企业，正渴望在生物制药领域找到突破口。而CSF，这个已被基础研究充分验证的靶点，进入了他们的视野。 将G-CSF从一种“活性”变成一个可以大规模生产的“分子”，需要其基因序列。这是一场艰苦卓绝的“基因狩猎”。 策略一：蛋白质纯化引领的“苦行僧”之路。 一支团队试图沿用经典生物化学方法：从大量能产生G-CSF的细胞（如某些肿瘤细胞株）培养上清中，一步步纯化出微量的天然G-CSF蛋白，再通过测定其部分氨基酸序列，反向推导出可能的基因序列。这个过程如同大海捞针，需要处理成千上升的培养液，经历层析、电泳等无数步骤，进展缓慢，且最终得到的蛋白量可能只够做几次测序。 策略二：表达克隆的“奇袭”。 与此同时，安进的科学家村上浩等人采用了一种更新锐、更依赖运气和洞察力的策略——表达克隆。他们选择了膀胱癌细胞株5637，因为已知其条件培养基中含有高活性的G-CSF。他们提取了这些细胞的全部信使RNA（mRNA），并将其反转录成互补DNA（cDNA）文库，然后将这些cDNA片段分别转入可以表达外源基因的宿主细胞（如猴肾细胞COS）。 关键的一步在于检测。他们将每个转染了cDNA的COS细胞培养上清，加入到含有小鼠骨髓细胞的培养体系中，然后日夜观察，寻找那个能刺激中性粒细胞集落形成的“神秘上清”。这需要建立极其灵敏、稳定的生物测定方法，并对数十万个克隆进行逐一筛查。 1986年，经过无数次的失败与尝试，奇迹发生了。一个特定的cDNA克隆被鉴定出来，当它表达的产物被加入骨髓细胞培养体系时，大量纯净的粒细胞集落蓬勃生长。他们成功克隆了人粒细胞集落刺激因子的基因。随后的测序分析揭示了其编码的蛋白质：一段由174个氨基酸组成的多肽链。 几乎同时，日本中外制药的科学家也独立克隆了G-CSF基因。科学的竞赛，以人类共同的胜利告终。获得基因，意味着可以利用重组DNA技术，让细菌（如大肠杆菌）或哺乳动物细胞变成高效的“G-CSF工厂”，无限生产这种原本在自然界中极其稀缺的蛋白质。 3 从“细菌工厂”到患者体内 ——非格司亭的诞生 有了基因，安进公司面临下一个抉择：选择哪种表达系统？这决定了最终药物的形式。 · 大肠杆菌系统：产量高、成本低，但表达的是非糖基化的蛋白，其氨基酸序列的N端比天然人G-CSF多一个蛋氨酸（因此被称为“甲硫氨酸化G-CSF”）。 · 哺乳动物细胞系统：能产生糖基化的蛋白，更接近天然人G-CSF的形式。 安进最终选择了大肠杆菌系统，生产的产物被命名为 “非格司亭” 。深入的临床前研究证明，这个多了一个蛋氨酸的重组蛋白，在生物活性、与受体的结合能力上，与天然G-CSF完全等效，甚至在体内外稳定性上可能更优。 接下来是严峻的临床试验。首要问题是：它安全吗？在人体内，外源的G-CSF会不会过度刺激骨髓，导致不受控的白细胞增多甚至白血病？会不会引发严重的自身免疫反应？ I期临床试验在健康志愿者和少量癌症患者中启动。结果令人鼓舞：非格司亭表现出卓越的安全性和明确的剂量依赖性升白效应。皮下注射后，外周血中性粒细胞数量在24小时内开始上升，并在几天内达到高峰。主要副作用是轻微的骨痛（与骨髓腔内的细胞快速增殖和扩张有关），以及注射部位的局部反应，均是可预测且可管理的。未观察到剂量限制性毒性及白血病转化等严重安全事件。 真正的考验在于能否改变临床结局。关键的随机、双盲、安慰剂对照III期临床试验随即展开，对象是接受高强度化疗（如用于小细胞肺癌的CAE方案）的癌症患者。一组患者在化疗后接受非格司亭注射，另一组接受安慰剂。 数据揭盲时，差异犹如云泥： · 中性粒细胞减少的深度和持续时间：非格司亭组显著改善。 · 中性粒细胞减少性发热的发生率：从安慰剂组的100% 骤降至非格司亭组的约28%。 · 住院和抗生素使用：大幅减少。 · 化疗的完成情况：非格司亭组患者更能按计划、足量地接受后续化疗周期。 这些数据强有力地证明，非格司亭不仅能提升白细胞数字，更能切实地降低致命感染风险，保障化疗的顺利进行。 4 获批与变革 ——肿瘤治疗范式的重塑 1991年2月，基于确凿的临床试验证据，美国FDA迅速批准了非格司亭（商品名：Neupogen）上市，用于预防化疗引起的中性粒细胞减少症及其相关并发症。 它的影响立竿见影，并深远地重塑了肿瘤学： 1. 直接拯救生命：无数像伊芙琳一样的患者，因为有了这道“白细胞高墙”，得以安然度过化疗后的骨髓抑制期，感染死亡率大幅下降。 2. 解放化疗的潜力：肿瘤医生可以更积极地使用剂量更强、密度更高的化疗方案（如剂量密集型疗法），而无需过度担忧骨髓毒性。这对于追求治愈的淋巴瘤、乳腺癌、睾丸癌等疾病至关重要，直接提高了部分癌症的治愈率。 3. 改善患者生活质量：减少了因感染导致的住院、使用静脉抗生素和医疗干预，让患者的治疗过程更加平稳、门诊化。 4. 催生支持治疗专科：非格司亭的成功，确立并极大地丰富了“肿瘤支持治疗”这一重要专科的内涵，使其成为与抗癌治疗并驾齐驱的支柱。 然而，非格司亭并非完美。它的半衰期仅约3.5小时，患者需要在化疗后每天进行一次皮下注射，持续7到14天甚至更久。这对于本就身心俱疲的癌症患者而言，是额外的负担和痛苦。 5 从每日到每周 ——长效化革命的序曲 非格司亭的局限性，催生了下一代产品的研发。科学家们开始思考：能否让G-CSF在体内停留更久？ 答案便是蛋白质长效化技术。2002年，安进推出了培非格司亭。其核心技术是将一个大的惰性聚乙二醇分子连接到非格司亭上（PEG化）。这个大分子如同一把“隐形伞”，既保护了G-CSF免遭肾脏快速清除，又改变了其药代动力学，将半衰期延长至数十小时。 结果是一场患者体验的革命：每个化疗周期，仅需在化疗结束后注射一次培非格司亭，即可覆盖整个中性粒细胞减少的风险窗口。它继承了非格司亭所有的疗效，同时极大提升了便利性、依从性和生活质量，迅速成为临床新标准。 培非格司亭的成功，正是站在非格司亭这位巨人的肩膀上。没有非格司亭从0到1的验证（G-CSF的安全有效性、临床价值），就不会有从1到10的长效化改进。 尾声 不朽的基石 今天，非格司亭的原研药已过专利期，多种生物类似药上市，价格更加可及。在培非格司亭等长效药物广泛应用的时代，它或许不再是首选，但从未被遗忘。它依然是干细胞动员、儿童患者、经济欠发达地区的重要工具与首选方案，更是全球无数无力承担长效药物的患者们可靠的生命防线。 回望非格司亭的发现史，它是一首多声部的交响乐： · 基础科学的好奇心（梅特卡夫的集落）提供了乐章的主题。 · 生物技术的勇气（安进的基因狩猎和表达克隆）谱写了激昂的旋律。 · 临床医学的迫切需求（化疗患者的死亡阴影）赋予了它深沉的情感与动力。 · 严谨的临床验证则确保了整部作品的和谐与辉煌。 非格司亭的故事告诉我们，伟大的药物发现，往往始于对生命最基本现象（几个细胞集落）的追问，成于跨越学科壁垒的技术融合，最终服务于人类最根本的健康需求。它或许不是最闪亮的那颗星，但作为第一个成功应用于临床的造血生长因子，它无疑是现代肿瘤支持治疗乃至整个生物制药时代的一块不朽基石。在每一剂保障化疗顺利进行的长效升白针背后，都伫立着非格司亭——这位沉默而伟大的先驱。 向下滑动查看 参考文献 1.  Metcalf, D. (2010). The discovery of the colony-stimulating factors. International Journal of Hematology, 91(5), 875-882.  2. Bradley, T. R., & Metcalf, D. (1966). The growth of mouse bone marrow cells in vitro. Australian Journal of Experimental Biology and Medical Science, 44(3), 287-300.  3. Nagata, S., Tsuchiya, M., Asano, S., Kaziro, Y., Yamazaki, T., Yamamoto, O., ... & Yamazaki, T. (1986). Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. Nature, 319(6052), 415-418.  4. Souza, L. M., Boone, T. C., Gabrilove, J., Lai, P. H., Zsebo, K. M., Murdock, D. C., ... & Altrock, B. (1986). Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science, 232(4746), 61-65.  5. Gabrilove, J. L., Jakubowski, A., Scher, H., Sternberg, C., Wong, G., Grous, J., ... & Clarkson, B. (1988). Effect of granulocyte colony-stimulating factor on neutropenia and associated morbidity due to chemotherapy for transitional-cell carcinoma of the urothelium. New England Journal of Medicine, 318(22), 1414-1422.  6. Crawford, J., Ozer, H., Stoller, R., Johnson, D., Lyman, G., Tabbara, I., ... & Smith, R. (1991). Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. New England Journal of Medicine, 325(3), 164-170.  7. Morstyn, G., & Foote, M. A. (2000). The history of granulocyte colony-stimulating factor. Hematology/Oncology Clinics of North America, 14(6), 1309-1333.  8.美国FDA药品说明书：Neupogen (filgrastim)的官方说明书，包含详细的药理学、临床试验数据和安全性信息。 9. Molineux, G. (2004). The design and development of pegfilgrastim (PEG-methionyl human granulocyte colony-stimulating factor, Neulasta). Current Pharmaceutical Design, 10(11), 1235-1244.  END 温馨提醒：本账号所有内容仅为科普分享，不能代替任何专业医疗建议。 封面图片为AI生成，请注意甄别。