MUC1

The trial assessed Leukine in 64 subjects with mild to moderate autoimmune pulmonary alveolar proteinosis. Credit: mi_viri / Shutterstock.com. The Japanese Pharmaceuticals and Medical Device Agency (PMDA) has granted approval for Partner Therapeutics’ Leukine (sargramostim) for inhaled use in treating autoimmune pulmonary alveolar proteinosis (aPAP). This is the first regulatory approval of an inhaled recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) product for this indication. In Japan, Leukine is branded as Sargmalin and was licensed to Nobelpharma in 2022 for certain indications. Leukine is a glycosylated recombinant human GM-CSF produced by recombinant DNA technology in yeast. Partner Therapeutics will execute the manufacturing of Sargmalin for Nobelpharma at its facility in Lynnwood, US. See Also: GSK expands Asia-Pacific reach for Trelegy Ellipta with Singapore approval UK MHRA approves Advanz Pharma antibiotic for complex infections The approval is based on the findings from the multicentre, randomised, double-blind, placebo-controlled Phase II PAGE study. It assessed Leukine in 64 subjects with mild to moderate aPAP. Subjects were randomised in a 1:1 ratio to receive either Leukine 125μg or a placebo twice a day for seven days, followed by seven days off, over 12 cycles of two weeks. The trial demonstrated a significant improvement on the primary endpoint, which was the improvement in the alveolar-arterial oxygen gradient from baseline to week 25. Subjects treated with Leukine also showed greater improvements in serum biomarker secondary endpoints, including KL-6, CEA and monocyte chemoattractant protein-1. Partner Therapeutics CEO Robert Mulroy stated: “We are grateful to Nobelpharma for their partnership, as well as their deep commitment to making this treatment available to aPAP patients in Japan. “It has been a pleasure working with their team and we look forward to ensuring the availability of Sargmalin. We also deeply appreciate the commitment of the many patients and doctors who participated in the investigator-initiated clinical trial led by Dr Nakata of Niigata University.”

Treatment will be Marketed by Nobelpharma Co. Ltd. Under the Trade Name Sargmalin® PMDA Approval of Sargmalin is the first regulatory approval of an inhaled recombinant GM-CSF product for aPAP LEXINGTON, Mass., April 3, 2024 /PRNewswire/ -- Partner Therapeutics, Inc. (PTx) announced that its partner Nobelpharma received approval from the Japanese Pharmaceuticals and Medical Device Agency (PMDA) for the inhaled use of Leukine (sargramostim), branded in Japan as Sargmalin, to treat aPAP. PTx licensed rights for certain indications in Japan to Nobelpharma in 2022. Leukine is a glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) produced by recombinant DNA technology in yeast. Leukine is not approved outside Japan for aPAP or as an inhalation therapy. Partner Therapeutics will manufacture Sargmalin for Nobelpharma at its manufacturing facility in Lynnwood, WA. The Sargmalin approval is based on data from the PAGE trial, a phase 2 multicenter, randomized, double-blind, placebo-controlled study to evaluate Leukine in 64 patients with mild to moderate aPAP led by Sponsor-Investigator Koh Nakata MD, PhD, Project Professor, Division of Pioneering Advanced Therapeutics, Center for Medical Innovation of Niigata University Medical Dental Hospital. Patients were randomly assigned 1:1 to receive either 125 micrograms of Leukine or placebo twice per day for seven days and then off for seven days for twelve two–week cycles. There was a significant improvement (p=0.02) in the primary endpoint of improvement in alveolar–arterial oxygen gradient (A-aDO2) between baseline and week 25. Greater improvements in serum biomarker secondary endpoints KL-6, CEA, and monocyte chemoattractant protein-1 (MCP-1) were observed with Leukine.1 "We are grateful to Nobelpharma for their partnership as well as their deep commitment to making this treatment available to aPAP patients in Japan," said Robert Mulroy, CEO of Partner Therapeutics. "It has been a pleasure working with their team and we look forward to ensuring availability of Sargmalin. We also deeply appreciate the commitment of the many patients and doctors who participated in the investigator-initiated clinical trial led by Dr. Nakata of Niigata University." Investigation of inhaled sargramostim, a recombinant human GM-CSF, in aPAP is based on knowledge that the disease is a progressive lung disorder driven by blockage of GM-CSF signaling due to the production of GM-CSF autoantibodies.1,2 The deficiency of GM-CSF in aPAP patients inhibits their ability to differentiate monocytes into alveolar macrophages, which causes aPAP patients to accumulate surfactant in their lungs. This dysfunction leads to low oxygen levels, difficulty breathing, innate immune deficiency, and, in some cases, serious infection, pulmonary fibrosis, respiratory failure, and death.2 GM-CSF improves lung function by directly acting on alveolar macrophages to promote their maturation and the breakdown of pulmonary surfactant by mature macrophages.3 To date, the standard treatment for aPAP has been Whole Lung Lavage (WLL), a lengthy and invasive procedure where saline is used to wash the lungs of excess surfactant. WLL requires hospitalization, general anesthesia, and mechanical ventilation. While effective in providing short term symptomatic relief, WLL can also have serious complications and does not treat alveolar macrophage dysfunction, the underlying cause of aPAP.4 REFERENCES Tazawa R, Ueda T, Abe M, et al. Inhaled GM-CSF for Pulmonary Alveolar Proteinosis. N Engl J Med. 2019;381(10):923-32. Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis. Progress in the first 44 years. Am J Respir Crit Care Med. 2002;166(2);215-35. Campo I, Carey BC, Paracchini E, Kadija Z, De Silvestri A, Rodi G, et al. Inhaled recombinant GM-CSF reduces the need for whole lung lavage and improves gas exchange in autoimmune pulmonary alveolar proteinosis patients. Eur Respir J 2024;63(1):2301233. McCarthy C, Carey BC and Trapnell BC. Autoimmune pulmonary alveolar proteinosis. Am J Respir Crit Care Med 2022;205(9):1016-1035. ABOUT LEUKINE LEUKINE (sargramostim) is a glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) produced by recombinant DNA technology in yeast. The product is commercially available in the United States and accessible through a named patient program operated by Tanner Pharma Group outside of the United States. LEUKINE is indicated: To shorten time to neutrophil recovery and to reduce the incidence of severe and life-threatening infections and infections resulting in death following induction chemotherapy in adult patients 55 years and older with acute myeloid leukemia (AML). For the mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis and autologous transplantation in adult patients. For the acceleration of myeloid reconstitution following autologous bone marrow or peripheral blood progenitor cell transplantation in adult and pediatric patients 2 years of age and older. For the acceleration of myeloid reconstitution following allogeneic bone marrow transplantation in adult and pediatric patients 2 years of age and older. For treatment of delayed neutrophil recovery or graft failure after autologous or allogeneic bone marrow transplantation in adult and pediatric patients 2 years of age and older. To increase survival in adult and pediatric patients from birth to 17 years of age acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome [H-ARS]). Important Safety Information for Leukine (sargramostim) Contraindications Do not administer LEUKINE to patients with a history of serious allergic reaction, including anaphylaxis, to human granulocyte-macrophage colony-stimulating factor, sargramostim, yeast-derived products, or any other component of LEUKINE. Warnings and Precautions Serious hypersensitivity reactions, including anaphylactic reactions, have been reported with LEUKINE. If a serious allergic or anaphylactic reaction occurs, immediately discontinue LEUKINE therapy, and institute medical management. Discontinue LEUKINE permanently for patients with serious allergic reactions. LEUKINE can cause infusion-related reactions that may be characterized by respiratory distress, hypoxia, flushing, hypotension, syncope, and/or tachycardia. Observe closely during infusion, particularly in patients with preexisting lung disease; dose adjustment or discontinuation may be needed. LEUKINE should not be administered simultaneously with or within 24 hours preceding cytotoxic chemotherapy or radiotherapy or within 24 hours following chemotherapy. Edema, capillary leak syndrome, and pleural or pericardial effusions have been reported in patients after LEUKINE administration. LEUKINE should be used with caution in patients with preexisting fluid retention, pulmonary infiltrates, or congestive heart failure. Such patients should be monitored. Supraventricular arrhythmia has been reported in uncontrolled studies during LEUKINE administration, particularly in patients with a history of cardiac arrhythmia. Use LEUKINE with caution in patients with preexisting cardiac disease. If absolute neutrophil count (ANC) > 20,000 cells/mm3 or if white blood cell (WBC) counts > 50,000/mm3, LEUKINE administration should be interrupted, or the dose reduced by half. Monitor complete blood counts (CBC) with differential twice per week. Discontinue LEUKINE therapy if tumor progression, particularly in myeloid malignancies, is detected during LEUKINE treatment. Treatment with LEUKINE may induce neutralizing anti-drug antibodies. Use LEUKINE for the shortest duration needed. Avoid administration of solutions containing benzyl alcohol (including LEUKINE for injection reconstituted with Bacteriostatic Water for Injection, USP [0.9 % benzyl alcohol]) to neonates and low birth weight infants. Drug Interactions Avoid the concomitant use of LEUKINE and products that induce myeloproliferation. Monitor for clinical and laboratory signs of excess myeloproliferative effects. Adverse Reactions Adverse events occurring in >10% of patients receiving LEUKINE in controlled clinical trials and reported at a higher frequency than in placebo patients are: In recipients of autologous bone marrow transplantation (BMT)–asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder In recipients of allogeneic BMT–abdominal pain, chills, chest pain, diarrhea, nausea, vomiting, hematemesis, dysphagia, GI hemorrhage, pruritus, bone pain, arthralgia, eye hemorrhage, hypertension, tachycardia, bilirubinemia, hyperglycemia, increased creatinine, hypomagnesemia, edema, pharyngitis, epistaxis, dyspnea, insomnia, anxiety, high glucose, low albumin In patients with AML–fever, weight loss, nausea, vomiting, anorexia, skin reactions, metabolic laboratory abnormalities, edema ABOUT PARTNER THERAPEUTICS Partner Therapeutics, Inc. (PTx), an integrated biotechnology company, focuses on development and commercialization of late-stage therapeutics to improve health outcomes in treatment of cancer and other serious diseases. The company believes in delivering products and supporting medical teams with the purpose of achieving superior outcomes for patients and their families. Visit . SOURCE Partner Therapeutics, Inc.

点击报名，与精鼎专家们切磋交流！虚位以待，诚聘英才！快快联系药时代！~正文共： 2192字 16图预计阅读时间： 6分钟导读肺癌是我国发病率第一的癌，腺癌是肺癌中最常见的病理类型。对于不可手术根治的晚期肺腺癌患者，一般采取非手术治疗方式，主要包括：放疗、化疗、靶向治疗、免疫治疗等。虽然Nivolumab等免疫检查点抑制剂可以延长总生存期(OS)和无进展生存期(PFS)，但只有少数患者从这些治疗中获益。在晚期非小细胞肺癌患者中，肿瘤免疫微环境限制了患者抗肿瘤免疫应答的诱导。因此，迫切需要新的治疗策略来增强免疫系统。由于树突状细胞(DC)在适应性免疫应答中的重要作用及其与免疫相关细胞的广泛串扰，DC疫苗可能是NSCLC患者最有前途的细胞疫苗接种策略之一。近日，Journal of Medical Case Reports杂志上发表了标题为“Dendritic cell vaccination in combination with erlotinib in a patient with inoperable lung adenocarcinoma: a case report.”的案例报道，报道了一例无法手术的肺腺癌患者，使用DC细胞疫苗联合靶向药物埃克替尼治疗后超过699天未发生复发或转移，实现“无癌”。图源 | jmedicalcasereports.biomedcentral.com患者信息：一位63岁女性患者，被诊断为左下叶IIIb期(T2aN3M0)肺腺癌，肿瘤大小为35mm×30mm。患者接受了基因检测，结果为：EGFR突变，ALK阴性，免疫组化显示PD-L1表达低于1%（EGFR、ALK为国内外指南常规推荐肺腺癌检测基因）。治疗过程：根据基因检测结果，患者首先接受了EGFR靶向治疗药物厄洛替尼的治疗。近一个月后，她开始接受厄洛替尼和一款名为WT1/MUC1-DC的DC疫苗联合治疗。单次接种后，可获得的疫苗更多，接种间隔更长。因此，在接种第8次疫苗开始，每隔约1-2个月接种两次WT1/MUC1-DC疫苗(约2×107细胞/次)。然后患者在接种第11至14次疫苗后每2个月接受常规剂量的WT1/MUC1-DC疫苗(约1×107个细胞/剂量)，以维持抗肿瘤免疫。最后一次接种(约1×107细胞/剂量)在14次接种后155天(治疗后699天)进行，一共接种15次WT1/MUC1-DC疫苗。治疗计划和肿瘤大小结果图源 | jmedicalcasereports.biomedcentral.com治疗效果：评价WT1/MUC1-DC疫苗的抗肿瘤免疫诱导作用是十分必要的。研究者通过接种部位的红斑大小和中性粒细胞与淋巴细胞比率(NLR)来评估抗肿瘤免疫的诱导。患者在第一次接种后48小时，接种部位出现了直径为30毫米的红斑。在接种过程中，这个红斑直径保持在20毫米以上。这些结果表明，该疫苗可能促进了抗肿瘤免疫反应。值得关注的是，经过237天的联合治疗后肿瘤大小显著减小至12毫米，缩小了65.7%。更令人兴奋的是，在经过321天的联合治疗后，CT扫描未发现肿瘤！甚至是治疗开始后699天，患者没有任何复发或转移的迹象！并且患者对WT1/MUC1-DC疫苗耐受性良好，在治疗期间内未观察到治疗相关的不良事件。 患者肺的CT和PET/CT结果图源 | jmedicalcasereports.biomedcentral.com结 语DC疫苗在前列腺癌、卵巢癌等实体肿瘤领域的数项研究中已经表现出良好的疗效，但在肺癌领域的探索尚处于初步阶段。继PD-1/L1抗体等免疫检查点抑制剂颠覆肺癌治疗之后，DC疫苗等自体细胞免疫疗法也有望走入大众的视野。该案例就是一个很好的探索，这位无法手术切除的肺腺癌患者在接受DC疫苗联合靶向治疗后获得了如此令人兴奋的结果提示DC疫苗在肿瘤治疗、抑制复发方面具有巨大潜力!参考文献：Takuya Kosumi , Masanori Kobayashi , Shigetaka Shimodaira , et. al. Dendritic cell vaccination in combination with erlotinib in a patient with inoperable lung adenocarcinoma: a case report. J Med Case Rep. 2024 Feb 10;18(1):88. doi: 10.1186/s13256-024-04363-z. PMID: 38336778. 封面图来源：123rf版权声明/免责声明本文为授权转载文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢!药时代官方网站:www.drugtimes.cn联系方式:电话:13651980212微信:27674131邮箱:contact@drugtimes.cn“绊倒”药王，有时只需一个联合疗法ADC药物开发策略、临床研究挑战以及中美CMC要求差异分析 | 药时代直播间9款药物折戟NASH/MASH领域中国新冠药登上《柳叶刀》子刊溢价100%也要拿下这家公司！MNC最新风向点击这里，在药时代里欢聚！~