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SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) for Genentech’s supplemental Biologics License Application (sBLA) for Columvi® (glofitamab-gxbm) in combination with gemcitabine and oxaliplatin (GemOx) for the treatment of people with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are not candidates for autologous stem cell transplant. Based on the CRL, the STARGLO data do not provide sufficient evidence to support the proposed second-line DLBCL indication in the U.S. patient population. STARGLO was also intended as a postmarketing confirmatory study to convert the accelerated approval of Columvi in third-line or later DLBCL in the U.S. to full approval. Columvi remains under accelerated approval for people with third-line or later DLBCL. Discussions with the FDA are ongoing to confirm the Phase III SKYGLO study investigating Columvi in combination with Polivy® (polatuzumab vedotin-piiq), Rituxan® (rituximab), cyclophosphamide, doxorubicin and prednisone for patients with previously untreated large B-cell lymphoma as the new postmarketing requirement. “While we are disappointed with this outcome, we remain confident in the data supporting the value of Columvi for U.S. patients who have relapsed following initial treatment, and its key role as monotherapy in the third-line setting,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We are committed to bringing Columvi to more people living with lymphoma and are actively exploring its potential in additional treatment settings, including as frontline therapy.” "For patients with this aggressive form of lymphoma, effective treatment after relapse is paramount. The STARGLO study showed that Columvi-GemOx significantly improves overall survival and could have a positive impact for patients earlier in their treatment journey. This regimen is already approved in over 35 countries, which underscores the urgent need it addresses," said Jeremy Abramson, M.D., director, Jon and Jo Ann Hagler Center for Lymphoma at the Massachusetts General Hospital Cancer Center, and principal investigator of the STARGLO study. Based on the STARGLO data, this Columvi combination is approved in more than 35 countries, including in the EU, and recommended in clinical practice guidelines including the U.S. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®).† Data has been submitted to other health authorities around the world for approval consideration. Columvi monotherapy has been approved for use in R/R DLBCL after two or more prior lines of therapy in more than 60 countries worldwide. The sBLA is based on results from the Phase III STARGLO study which showed a statistically significant and clinically meaningful 41% reduction in the risk of death (hazard ratio=0.59, 95% confidence interval: 0.40–0.89, p=0.011) in patients treated with Columvi in combination with GemOx. Results were published in The Lancet and two-year follow-up data from the study were presented at the 61st American Society of Clinical Oncology Annual Meeting from May 30 – June 3, 2025, where improvements in primary and secondary endpoints were sustained. †NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. About the STARGLO study The STARGLO study [GO41944; NCT04408638] is a Phase III, multicenter, open-label, randomized study evaluating the efficacy and safety of Columvi® (glofitamab-gxbm) in combination with gemcitabine plus oxaliplatin (GemOx) versus Rituxan® (rituximab) in combination with GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma who have received at least one prior line of therapy and who are not candidates for autologous stem cell transplant, or who have received two or more prior lines of therapy. Preclinical research indicated an increased antitumor effect when combining Columvi with GemOx over GemOx alone, so the STARGLO study was initiated to further explore the potential complementary effects of the treatment combination. Outcome measures include overall survival (primary endpoint), progression-free survival, complete response rate, objective response rate, duration of objective response (secondary endpoints), and safety and tolerability. About Columvi® (glofitamab-gxbm) Columvi is a CD20xCD3 T-cell engaging bispecific antibody designed to target CD3 on the surface of T cells and CD20 on the surface of B cells. Columvi was designed with a novel 2:1 structural format. This T-cell-engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T cells, a type of immune cell, and two regions that bind to CD20, a protein on B cells, which can be healthy or malignant. This dual-targeting brings the T cell in close proximity to the B cell, activating the release of cancer cell-killing proteins from the T cell. Columvi is part of Genentech’s broad and industry-leading CD20xCD3 T-cell-engaging bispecific antibody clinical development program, which aims to provide tailored treatment options that suit the diverse needs, preferences, and experiences of people with blood cancers and healthcare systems. Genentech is investigating Columvi as a monotherapy and in combination with other medicines for the treatment of diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma. As part of Genentech’s efforts to elevate treatment standards in the earlier stages of DLBCL, where there is the best opportunity to improve long-term outcomes and prevent relapse, Columvi is also being investigated in combination with other medicines in previously untreated DLBCL in the Phase III SKYGLO study [GO44145; NCT06047080]. About diffuse large B-cell lymphoma (DLBCL) Diffuse large B-cell lymphoma (DLBCL) is an aggressive (fast-growing) blood cancer and is the most common form of non-Hodgkin’s lymphoma in the U.S. Approximately 160,000 people worldwide are diagnosed with DLBCL each year, with comparable incidence rates across regions. Medical practices, including pathological classification, diagnosis, staging, initial treatment and relapse management, are similarly approached worldwide. While it is generally responsive to treatment in the frontline, as many as 40% of people will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short. Improving treatments earlier in the course of the disease and providing much-needed alternative options could help to improve long-term outcomes. Columvi U.S. Indication Columvi (glofitamab-gxbm) is a prescription medicine to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) or large B-cell lymphoma (LBCL) that has come back (relapsed) or that did not respond to previous treatment (refractory), and who have received 2 or more prior treatments for their cancer. It is not known if Columvi is safe and effective in children. The conditional approval of Columvi is based on response rate and durability of response. There are ongoing studies to establish how well the drug works. What is the most important information I should know about Columvi? Columvi can cause Cytokine Release Syndrome (CRS), a serious side effect that is common during treatment with Columvi, and can also be serious and lead to death. Call your healthcare provider or get emergency medical help right away if you develop any signs or symptoms of CRS, including: fever of 100.4°F (38°C) or higher chills or shaking fast or irregular heartbeat dizziness or light-headedness trouble breathing shortness of breath Due to the risk of CRS, you will receive Columvi on a “step-up dosing schedule”. A single dose of a medicine called obinutuzumab will be given to you on the first day of your first treatment cycle (Day 1 of Cycle 1). You will start the Columvi step-up dosing schedule a week after the obinutuzumab dose. The step-up dosing schedule is when you receive smaller “step-up” doses of Columvi on Day 8 and Day 15 of Cycle 1. This is to help reduce your risk of CRS. You should be hospitalized during your infusion and for 24 hours after receiving the first step-up dose on Day 8. You should be hospitalized during your infusion and for 24 hours after receiving the second step-up dose on Day 15 if you experienced CRS during the first step-up dose. You will receive your first full dose of Columvi a week after the second step-up dose (this will be Day 1 of Cycle 2). If your dose of Columvi is delayed for any reason, you may need to repeat the “step-up dosing schedule”. If you had more than mild CRS with your previous dose of Columvi, you should be hospitalized during and for 24 hours after receiving your next dose of Columvi. Before each dose of Columvi, you will receive medicines to help reduce your risk of CRS and infusion-related reactions. Your healthcare provider will monitor you for CRS during treatment with Columvi and may treat you in a hospital if you develop signs and symptoms of CRS. Your healthcare provider may temporarily stop or completely stop your treatment with Columvi if you have severe side effects. Carry the Columvi Patient Wallet Card with you at all times and show it to all of your healthcare providers. The Columvi Patient Wallet Card lists the signs and symptoms of CRS you should get emergency medical help for right away. What are the possible side effects of Columvi? Columvi may cause serious side effects, including: Neurologic problems. Columvi can cause serious neurologic problems that may lead to death. Your healthcare provider will monitor you for neurologic problems during treatment with Columvi. Your healthcare provider may also refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any signs or symptoms of neurologic problems, including: headache confusion and disorientation difficulty paying attention or understanding things trouble speaking sleepiness memory problems numbness, tingling, or weakness of the hands or feet dizziness shaking (tremors) headache confusion and disorientation difficulty paying attention or understanding things trouble speaking sleepiness memory problems numbness, tingling, or weakness of the hands or feet dizziness shaking (tremors) Serious Infections. Columvi can cause serious infections that may lead to death. Your healthcare provider will monitor you for signs and symptoms of infection and treat you as needed. Tell your healthcare provider right away if you develop any signs of an infection, including: fever, chills, weakness, cough, shortness of breath, or sore throat. Tell your healthcare provider if you get any of these signs or symptoms of tumor flare: tender or swollen lymph nodes pain or swelling at the site of the tumor chest pain cough trouble breathing The most common side effects of Columvi include: CRS, muscle and bone pain, rash, and tiredness. The most common severe abnormal lab test results with Columvi include: decreased white blood cells, decreased phosphate (an electrolyte), increased uric acid levels, and decreased fibrinogen (a protein that helps with blood clotting). Your healthcare provider may temporarily stop or completely stop treatment with Columvi if you develop certain side effects. Before receiving Columvi, tell your healthcare provider about all of your medical conditions, including if you: have an infection have kidney problems are pregnant or plan to become pregnant. Columvi may harm your unborn baby Your healthcare provider should do a pregnancy test before you start treatment with Columvi. You should use effective birth control (contraception) during treatment and for 1 month after your last dose of Columvi. Talk to your healthcare provider about what birth control method is right for you during this time. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Columvi. are breastfeeding or plan to breastfeed. Columvi may pass into your breast milk. Do not breastfeed during treatment and for 1 month after your last dose of Columvi. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. What should I avoid while receiving Columvi? Do not drive, operate heavy machinery, or do other dangerous activities if you develop dizziness, confusion, shaking (tremors), sleepiness, or any other symptoms that impair consciousness until your signs and symptoms go away. These may be signs and symptoms of neurologic problems. These are not all the possible side effects of Columvi. Talk to your health care provider for more information about the benefits and risks of Columvi. You may report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555. Please see Important Safety Information, including Serious Side Effects, as well as the Columvi full Prescribing Information and Medication Guide or visit https://www.Columvi.com About Polivy® (polatuzumab vedotin-piiq) Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed in the majority of B cells, an immune cell impacted in some types of non-Hodgkin lymphoma (NHL), making it a promising target for the development of new therapies. Polivy binds to cancer cells such as those expressing CD79b and destroys these B cells through the delivery of an anti-cancer agent, which is thought to minimize the effects on normal cells. Polivy is being developed by Genentech using Pfizer ADC technology and is currently being investigated for the treatment of several types of NHL. Polivy U.S. Indication Polivy is a prescription medicine used with other medicines (a rituximab product, cyclophosphamide, doxorubicin, and prednisone) as a first treatment for adults who have moderate to high risk diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) or high-grade B-cell lymphoma (HGBL). Polivy is a prescription medicine used with other medicines, bendamustine and a rituximab product, to treat DLBCL in adults who have progressed after at least 2 prior therapies. Important Safety Information Possible serious side effects Everyone reacts differently to Polivy therapy, so it’s important to know what the side effects are. Some people who have been treated with Polivy have experienced serious to fatal side effects. Your doctor may stop or adjust your treatment if any serious side effects occur. Be sure to contact your healthcare team if there are any signs of these side effects. Nerve problems in your arms and legs: This may happen as early as after your first dose and may worsen with every dose. Your doctor will monitor for signs and symptoms, such as changes in your sense of touch, numbness or tingling in your hands or feet, nerve pain, burning sensation, any muscle weakness, or changes to your walking pattern Infusion-related reactions: You may experience fever, chills, rash, breathing problems, low blood pressure, or hives within 24 hours of your infusion Low blood cell counts: Treatment with Polivy can cause severe low blood cell counts. Your doctor will monitor your blood counts throughout treatment with Polivy Infections: If you have a fever of 100.4°F (38°C) or higher, chills, cough, or pain during urination, contact your healthcare team. Your doctor may also give you medication before giving you Polivy, which may prevent some infections Rare and serious brain infections: Your doctor will monitor closely for signs and symptoms of these types of infections. Contact your doctor if you experience confusion, dizziness or loss of balance, trouble talking or walking, or vision changes Tumor lysis syndrome: Caused by the fast breakdown of cancer cells. Signs include nausea, vomiting, diarrhea, and lack of energy Potential harm to liver: Some signs include tiredness, weight loss, pain in the abdomen, dark urine, and yellowing of your skin or the white part of your eyes. You may be at higher risk if you already had liver problems or you are taking other medication Side effects seen most often The most common side effects during treatment were Nerve problems in arms and legs Nausea Tiredness or lack of energy Diarrhea Constipation Hair loss Redness and sores of the lining of the mouth, lips, throat, and digestive tract Polivy may lower your red or white blood cell counts and increase uric acid levels. Polivy may not be for everyone. Talk to your doctor if you are Pregnant or think you are pregnant: Data have shown that Polivy may harm your unborn baby Planning to become pregnant: Women should avoid getting pregnant while taking Polivy. Women should use effective contraception during treatment and for 3 months after their last Polivy treatment. Men taking Polivy should use effective contraception during treatment and for 5 months after their last Polivy treatment Breastfeeding: Women should not breastfeed while taking Polivy and for 2 months after the last dose These may not be all the side effects. Talk to your healthcare provider for more information about the benefits and risks of Polivy treatment. You may report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555. Please see the full Prescribing Information and visit https://www.Polivy.com for additional Important Safety Information. About Genentech in hematology For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. For more information visit http://www.gene.com/hematology. About Genentech Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Genentech Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

关注并星标CPHI制药在线中药自组装是指中药活性成分由于非共价键力，即氢键、静电力、范德华力、π-π 堆积等相互作用，自发排列成有序结构（如纳米颗粒、纳米纤维、胶束和囊泡）的过程。研究发现，中药从生药、炮制、煎煮、制剂的成型和储存以及最终给药到体内等多个阶段都存在自组装现象。中药材含有多种不同的活性成分，包括生物碱、黄酮类化合物、多糖、挥发油、苷类、鞣质等，这些成分具有不同的药理作用和药效。它们之间的自组装行为可以发生在同种成分中，也可发生在不同成分间。如多糖类结构中含有大量的亲水基团，其可以通过氢键或疏水基团与其他结构自组装成不同复合物，进而实现药理作用的改善。蛋白质分子间自组装以弱相互作用为主，通过氢键、范德华力、静电、疏水作用等多种作用力的加合而成。三萜类化合物在自然界中广泛存在，人参、甘草、紫苏、黄芪等多种中药中都含有多种三萜的苷元及苷。三萜类化合物具有独特的手性结构、多修饰位点、良好的生物相容性和可控的降解性。三萜类化合物自组装的形成主要是通过其刚性骨架间的范德华作用以及分子间的氢键实现的。中药自组装的研究应用1、作为天然纳米载体中药汤剂自组装不仅具有人工合成纳米材料一样的药物包封能力，还具有优于人工合成纳米材料的生物可降解性、生物相容性和安全性，可以作为天然纳米载体，用于药物递送，改善药物的生物利用度，增强药物疗效。目前，苦杏仁蛋白自组装纳米颗粒、太子参蛋白自组装纳米颗粒及生姜脂质自组装纳米颗粒等已被成功用于抗肿瘤药物紫杉醇、姜黄素及多柔比星等的递送。甘草有效成分甘草酸具有两亲性，能够聚集形成自组装胶束，作为多功能药物载体被广泛用于改善药物吸收。此外，生姜脂质自组装纳米颗粒可以结肠靶向递送 siRNA 用于结肠炎的治疗，同时可能具有协同抗炎疗效；甘草蛋白自组装纳米颗粒能够包载附子毒性成分乌头碱以降低其毒性反应。2、作为抗菌材料纳米抗菌是指利用纳米技术开发的一种抗菌技术，纳米级的材料具有较大的比表面积和独特的物理、化学性质，因此在抗菌方面具有独特的优势。无机纳米银是当前研究最广泛的无机抗菌材料，其具有抑菌能力强、耐高温、安全性好等优点，但也存在产率低、造价高、毒性不确定等缺点。天然纳米抗菌剂具有抗菌性好、无毒性、绿色安全等优势，逐渐进入了人们的视野。研究发现，从芍药甘草汤中分离出的自组装纳米颗粒可以降低多种炎症因子的表达水平，减少炎性细胞浸润等，从而达到治疗银屑病小鼠的目的。天然中药提取物小檗碱与肉桂酸可以通过氢键和π-π堆积自组装形成蝶形三维结构纳米颗粒，该纳米颗粒具有良好的抑菌活性，对耐多药金黄色葡萄球菌（methicillin-resistant Staphylococcus aureus，MRSA）有较好的抑制作用，并具有更强的生物膜去除能力，其生物相容性和连续释放特性良好，毒性也较小。3、降低毒性作用甘草具有解百毒的功效，常在组方中起解毒、调和诸药的作用。《本草纲目·草部第十二卷》引甄权语："诸药中甘草为君，治七十二种乳石毒，解一千二百般草木毒，调和众药有功，故有国老之号。"甘草常与雷公藤、马钱子、附子等配伍，起到减毒的作用。研究发现，甘草和附子在煎煮过程中蛋白质会发生自组装行，通过自组装，甘草蛋白与乌头碱可形成平均粒径为（238.20±1.23）nm 的甘草蛋白-乌头碱稳定胶体颗粒。通过小鼠急性毒性实验发现，注射乌头碱单体的小鼠全部死亡，而注射相同乌头碱含量的甘草蛋白-乌 头碱颗粒的小鼠全部存活，且该胶体颗粒在室温下较稳定，具有成为药物候选载体的可能性。4、增溶作用中药汤剂中包含了许多种难溶性成分，部分中药纳米自组装颗粒通过自发性的亲疏水作用或表面修饰的相互作用实现纳米粒子组装。在这个过程中，其特殊的结构特性，可以改善疏水药物的水溶性。如三萜皂苷类成分具有表面活性剂的性质，可起到增溶的作用。研究发现，甘草中三萜皂苷类成分甘草酸同时存在亲水和疏水部分，有类似表面活性剂的结构特点，可以自组装形成凝胶纳米聚集体。随着甘草酸的浓度增加，薯蓣皂苷元和齐墩果酸在水溶液中的溶解度呈上升趋势，甘草酸溶液的浓度达到 1 mmol·L⁻¹时，薯蓣皂苷元及齐墩果酸的溶解度均增加约 60倍，薯蓣皂苷元的溶解度由 6.15 ng·mL⁻¹提升到了 360.59 ng·mL⁻¹，齐墩果酸的溶解度由 20.09 ng·mL⁻¹提升到了  1155.36 ng·mL⁻¹。5、在抗肿瘤方面的研究中药自组装纳米颗粒联合化疗药物进行抗肿瘤治疗不仅可以提高化疗药物的溶解度和稳定性，还能增强其靶向和释放能力，通过不同的抗肿瘤途径达到协同增效的目的。研究发现，从苦杏仁中分离出的11S 球蛋白进行热处理时存在自组装行为，结合键类型主要以二硫键、氢键为主。在碱性环境下，蛋白质浓度越高，自组装发生的速率越快；温度越高，形成的纳米颗粒的粒径越大，且形成的纳米颗粒具有良好的低温稳定性。通过用该纳米颗粒装载抗癌药物苦杏仁苷与紫杉醇，可以提升抗癌药物对癌细胞增殖的抑制作用，对人乳腺癌细胞（human breast cancer cells，MCF-7）增殖抑制率提高了42.88%。熊果酸（ursolic acid，UA）是一种三萜类化合物，具有抗肿瘤转移、抗血管生成、抗炎和抗增殖的潜力作用，是天然植物夏枯草或铁冬青的有效成分之一。表没食子儿茶素没食子酸酯（epigallocatechin gallate，EGCG）是绿茶中含量较丰富的成分之一，具有抗肿瘤、抗氧化和心血管保护能力。 UA 与EGCG 可以通过氢键和疏水作用自组装成纳米粒，通过上皮细胞黏附分子（epithelial cell adhesion molecule，EpCAM）适配体修饰的 UA 和EGCG 的无载体、自组装的纳米药物，用于靶向荷瘤小鼠肝细胞癌（hepatocellular carcinoma，HCC）治疗，发现该自组装纳米颗粒能明显抑制肿瘤生长，且对小鼠无明显的毒性。6、揭示中药配伍机制研究中药自组装的发现有助于以新的视角揭示中药复方配伍减毒增效的作用机制。中药自组装的形成既能够包载活性成分，产生增溶及促吸收作用，增强疗效；也可以包载毒性成分，延缓或抑制毒性成分的吸收，减弱毒副作用。研究发现，葛根芩连汤自组装的形成能够促进黄芩苷的吸收及抗氧化活性；麻杏石甘汤中形成的自组装能够包载其有效成分麻黄碱和伪 麻黄碱，表现出不同的细胞（Caco-2、L-02、Hep G2、NR-8383、HeLa-229）增殖抑制活性；白虎汤中形成的自组装相比其他部位（溶液或沉淀）具有更好的解热作用，与全方的解热作用一致，且具有一定的肺脑靶向性。此外，中药小分子有效成分可以参与自组装的形成，有利于其自身的吸收和细胞摄取，表现出更强的生物活性。黄连有效成分小檗碱可以与黄芩有效成分黄芩苷自组装球形成纳米粒，该自组装具有显著优于小檗碱的抗菌活性，且显示出与黄连解毒汤类似的神经细胞保护作用，这在一定程度上揭示了黄连解毒汤的配伍增效机制。7、中药新药发现新策略中药自组装的发现不仅有助于揭示中药配伍理论的科学内涵，还为中药新药的开发提供了新策略。中药汤剂自组装的形成不仅影响有效成分的吸收，还可能具有优于有效成分或其简单混合物的生物活性。如果自组装的形成只是通过促进有效成分的吸收而增强药效，则可以将有效成分分离纯化，采用新型递药技术促进有效成分的吸收，增强药效；这样能够有效避免中药物质基础复杂、作用机制不清及质控困难等问题。若是中药汤剂自组装的形成表现出显著优于有效成分或其简单混合物的生物活性，则表明自组装可能是中药及复方药效发挥的物质基础真实形态，以自组装为基础开发新药，可能具有更好的成药性，这无疑为中药新药的开发提供了一种全新的研究策略。参考资料：[1]李斌,王慧敏,刘善钊.中药汤剂自组装技术的研究进展[J].西北药学杂志,2025,40(01):225-234.[2]沈成英,胡菲,朱君君,等.中药自组装纳米粒的形成及应用研究进展[J].中国中药杂志,2021,46(19):4875-4880.作者简介：小米虫，药品质量研究工作者，长期致力于药品质量研究及药品分析方法验证工作，现就职于国内某大型药物研发公司，从事药品检验分析及分析方法验证。END来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~