Daratumumab/Hyaluronidase-fihj

12月17日。药物临床试验登记与信息公示网站显示，齐鲁制药启动了达雷妥尤单抗生物类似药皮下注射剂型（QL2109）的首个III期研究。这是首个进入III期阶段的达雷妥尤单抗生物类似药皮下注射剂型。 该研究是一项随机、双盲、多中心III期临床试验（n=284），旨在评估QL2109联合泊马度胺和地塞米松对比Darzalex Faspro（达雷妥尤单抗皮下制剂，强生）联合泊马度胺和地塞米松治疗复发性或难治性多发性骨髓瘤成年患者的有效性和安全性。研究的主要终点为第24周达到非常好的部分缓解及以上（≥VGPR）的患者比例。 原研达雷妥尤单抗（Daratumumab）是强生多年前自Genmab引进的一款抗CD38单抗，强生拥有该产品的所有权益。2015年11月，达雷妥尤单抗静脉注射剂型（商品名：Darzalex）获FDA加速批准，用于治疗先前至少接受过3种治疗（包括蛋白酶体抑制剂和免疫调节剂）或对蛋白酶体抑制剂和免疫调节剂双重耐药的多发性骨髓瘤患者。该项批准在2016年11月转换为常规批准，适应症调整为联合来那度胺和地塞米松或联合硼替佐米和地塞米松治疗既往至少接受过一种治疗的多发性骨髓瘤患者。 截至目前，Darzalex在美国已获批6项适应症，包括： 联合来那度胺和地塞米松或联合硼替佐米和地塞米松治疗既往至少接受过一种治疗的多发性骨髓瘤患者； 联合泊马度胺和地塞米松治疗先前至少接受过两种治疗（包括来那度胺和蛋白酶体抑制剂）的多发性骨髓瘤患者； 联合硼替佐米、美法仑和泼尼松治疗不适合自体干细胞移植的新诊断多发性骨髓瘤患者； 联合来那度胺和地塞米松治疗不适合自体干细胞移植的新诊断患者以及先前至少接受过一种治疗的复发或难治性多发性骨髓瘤患者； 联合硼替佐米、沙利度胺和地塞米松治疗适合自体干细胞移植的新诊断患者； 联合卡非佐米和地塞米松治疗接受过1-3种治疗的复发性或难治性多发性骨髓瘤患者。 2020年5月，强生基于Halozyme Therapeutics的皮下递送技术开发的达雷妥尤单抗皮下注射剂型（商品名：Darzalex Faspro）在美国获批上市。 根据强生财报，Darzalex在2023年创造的销售额为97.44亿美元。今年前三季度，Darzalex销售额已达到85.86亿美元。 目前，全球尚无达雷妥尤单抗生物类似药获批上市。医药魔方Nextpharma数据库显示，共8款达雷妥尤单抗生物类似药处于在研状态，来自Biocad、齐鲁制药、复宏汉霖、正大天晴等公司。其中，仅九源基因和齐鲁制药开发了达雷妥尤单抗生物类似药皮下注射剂型。 Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。 免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

The annual meeting of the American Society of Clinical Oncology drew more than 30,000 attendees to San Diego, and more who participated in the conference virtually, all of them looking to see and hear the latest developments in blood cancers and hematological disorders. Multiple myeloma is always a big topic of discussion at the annual ASH meeting, and developments this year include clinical data supporting the use of certain therapies in even earlier lines of treatment. On the cell therapy front, there is an ongoing effort to improve the manufacturability of these treatments. Data were presented demonstrating shorter “vein-to-vein times,” the time from when cells are harvested to when therapeutic cells are infused into the patient. And in sickle cell disease, encouraging early data were presented showing promise for a gene-editing therapy that could offer patients a one-time treatment. We couldn’t catch everything at what is one of the biggest medical meetings of the year. Here’s a recap of some highlights from the ASH 2024 meeting: Sponsored Post The Funding Model for Cancer Innovation is Broken — We Can Fix It Closing cancer health equity gaps require medical breakthroughs made possible by new funding approaches. By Eve McDavid - CEO of Mission-Driven Tech Movement in Multiple Myeloma —GSK reported Phase 3 data that support bringing the multiple myeloma drug Blenrep back to the market. The latest results show a Blenrep drug regimen, as a second-line of treatment, helped patients live longer compared against a drug regimen that includes the blockbuster Johnson & Johnson drug Darzalex. These results at ASH follow a Phase 3 data readout earlier this year showing Blenrep beat a drug combination that includes the Bristol Myers Squibb cancer drug Pomalyst. Blenrep won accelerated approval in 2020. GSK withdrew Blenrep from the market after it failed a confirmatory Phase 3 study. But that test evaluated the drug as a monotherapy and as a fifth line of treatment. The Phase 3 studies that are part of regulatory submissions currently under review tested the drug in combination with other multiple myeloma therapies and as an earlier line of treatment. GSK’s plans for the drug include a study underway that could support expanding the drug’s use to first-line multiple myeloma treatment, where its competition will include Darzalex. —Speaking of Darzalex, Johnson & Johnson reported data for an injectable formulation of the drug, Darzalex Faspro, as a treatment for smoldering multiple myeloma, which is an asymptomatic precursor to this type of blood cancer. In smoldering multiple myeloma, patients have high levels of abnormal plasma cells and elevated levels of monoclonal protein in the blood. presented by Market Trends to Watch for Health Systems and Their Specialty Pharmacies The future looks bright for the integrated specialty pharmacy model – for health systems, providers, and most importantly, for patients. By Jake Gaffey, MBA, Chief Strategy Officer at Shields Health Solutions In a Phase 3 test that enrolled 390 participants, J&J’s Darzalex Faspro significantly delayed high-risk smoldering multiple myeloma from progressing to active disease. The drug also extended overall survival compared to active monitoring, which is the current standard of care. Darzalex Faspro currently has nine approvals in multiple myeloma. Last month, the company submitted applications in the U.S. and Europe seeking to add smoldering multiple myeloma to the product’s list of approved indications. —Arcellx’s BCMA-targeting cell therapy, anito-cel, posted Phase 2 results in multiple myeloma that analysts say are comparable to Carvykti from partners Legend Biotech and Johnson & Johnson. It’s the safety results that reinforce their view of the Arcellx cell therapy as potentially best in class. Carvykti’s trials showed some cases of delayed neurological toxicities, including parkinsonism, a movement disorder. Arcellx is engineered to offer better safety and the results so far show no signs of parkinsonism. Analysts say Arcellx also has advantages through its partnership with Gilead Sciences, which has a global cell therapy manufacturing infrastructure and experience commercializing such products. —J&J and Legend added to the body of evidence showing that Carvykti is helping multiple myeloma patients live longer compared to standard therapies. The Phase 3 study, which tested the cell therapy in patients who had received one to three prior lines of therapy, showed that after a median 33.6 months of follow-up, Carvykti led to significantly increased rates of rates of minimal residual disease negativity, a marker of survival outcomes for multiple myeloma patients. A Look at Leukemia & Lymphoma Drugs —Kura Oncology reported more detailed data for ziftomenib, a drug candidate now partnered with Kyowa Kirin. The small molecule menin inhibitor is being developed to treat leukemias driven by certain genetic mutations. Results from the Phase 1 dose-escalation study showed a 100% complete response rate in those with NPM1 mutations. In patients whose disease harbored KMT2A mutations, the complete response rate was 83%. The companies said the drug was safe and well tolerated in combination with standard of care therapies. Last month, Kyowa Kirin paid $330 million to begin the alliance on ziftomenib. If the drug reaches the market, it will compete against Revuforj, a Syndax Pharmaceuticals menin inhibitor that won FDA approval in November. —Eli Lilly drug Jaypirca landed accelerated FDA approval last year as a treatment for advanced cases of mantle cell lymphoma following at least two prior lines of therapy. At the ASH conference, Lilly reported Phase 3 data that could support full approval for the drug, a small molecule inhibitor of a protein called BTK. Results show Jaypirca reduced the risk of disease progression or death by 46% compared to standard treatments. Treatment with the Lilly drug also prolonged the time to the next treatment or death by a median 23.9 months. Lilly said the safety profile of Jaypirca in Phase 3 was consistent with the Phase 1/2 test used to support the drug’s accelerated approval. —In a pre-planned analysis of a Phase 2 clinical trial in diffuse large B-cell lymphoma, Merck’s experimental drug zilovertamab vedotin led to a 97.2% complete response rate. What kept the study from achieving the 100% mark was discontinuation of two participants by physician decision, one patient each in the middle- and high-dose cohorts. All participants in the low-dose group showed a complete response. Based on the clinical trial results for the drug candidate, an antibody drug conjugate (ADC), Merck has selected the low dose to advance to Phase 3 testing. The results so far are encouraging for this therapy and others developed to seek out ROR1, a novel target currently unaddressed by any approved drugs. Other companies developing ROR1-targeting ADCs include Ipsen, which licensed its candidate from Sutro Biopharma earlier this year, and CStone Pharmaceuticals. Sickle Cell Disease Developments —Last month, Beam Therapeutics teased encouraging early clinical results for six patients dosed with BEAM-101, a gene-editing therapy for sickle cell disease. Updated data at ASH put some figures to the results as of an Oct. 28 data cutoff. Results showed these patients achieved fetal hemoglobin levels exceeding 60% and a reduction in sickle-shaped hemoglobin below 40% at month 1. Those levels were sustained to the last time point available, indicating that the effects of the one-time treatment are durable so far. The therapy’s safety profile was consistent with that of busulfan, the conditioning therapy that is used to prepare a patient to receive BEAM-101. As previously reported, there was one fatality from respiratory failure, which investigators attributed to busulfan. In all six patients dosed, there have been no serious adverse events attributed to BEAM 101. —Novo Nordisk presented Phase 2 data for etavopivat showing the once-daily oral drug led to a reduction in vaso-occlusive crises, a complication of sickle cell disease. The one-year, proof-of-concept study also showed an increase in hemoglobin levels. With these results, Novo Nordisk said it has selected the dose to test in a Phase 3 clinical trial. Etavopivat came to Novo Nordisk from the $1.1 billion acquisition of Forma Therapeutics in 2022. Catching Up on Cell Therapies —The cancer target GPRC5D is currently addressed by only one FDA-approved drug, the Johnson & Johnson bispecific antibody Talvey, a treatment for multiple myeloma. Bristol Myers Squibb aims to be the first to drug GPRC5D with a cell therapy. At the ASH meeting, BMS presented Phase 1 data showing its candidate, arlocabtagene autoleucel (arlo-cel), led to durable responses that deepened over time. Bristol says these results support arlo-cel as a potential first-in-class treatment for relapsed or refractory multiple myeloma in heavily pretreated patients. A Phase 2 test of the cell therapy is ongoing. —Galapagos’s non-Hodgkin lymphoma cell therapy candidate GLPG5101 posted additional Phase 1/2 results showing encouraging efficacy and safety. The company also pointed out that the vein-to-vein time was a median seven days. By comparison, the multi-step manufacturing process for currently available cell therapies can take a month or more. Galapagos’s process leverages Cocoon, a point-of-care manufacturing system from contract manufacturing giant Lonza. —Orca Bio posted data for Orca-T, an allogeneic T-cell immunotherapy in testing as a treatment for three types of blood cancer: acute myeloid leukemia, acute lymphoblastic leukemia, and high-risk myelodysplastic syndrome. Results from a three-year follow-up analysis from Phase 1b showed an overall survival rate of 86% for the study drug compared to 67% in a non-randomized historical group that received an allogeneic stem cell transplant. Orca-T is comprised of highly purified immune cells from donors. In the Phase 1b test, Orca Bio said this allogeneic therapy was manufactured reliably with vein-to-vein time of 72 hours or less across the U.S. An ongoing Phase 3 test comparing Orca-T to conventional allogeneic stem cell transplants is expected to report preliminary data in the first half of 2025. A Recap in Rare Blood Disease —Sanofi revealed details of its Phase 3 test of rilzabrutinib in persistent or chronic immune thrombocytopenia, a rare immune disorder leading to low platelet levels. Results show the small molecule BTK inhibitor led to platelet response in 65% of patients in the study drug arm compared to 33% of those who received a placebo. Furthermore, a durable platelet response was observed in 23% of patients who received rilzabrutinib versus zero in the placebo group. The drug, which came from the $3.7 billion acquisition of Principia Biopharma in 2020, is currently under regulatory review in the U.S. and Europe. —Standard of care for the rare blood disorder paroxysmal nocturnal hemoglobinuria (PNH) includes two blockbuster AstraZeneca drugs, Soliris and Ultomiris, though Apellis Pharmaceuticals and Novartis are trying to take market share with their FDA-approved therapies. Regeneron Pharmaceuticals aims to compete with those complement inhibitors with a drug combination: the approved antibody pozelimab (brand name Veopoz) and the experimental RNA-interference therapy cemdisiran. A Phase 3 test is underway testing the combination against Soliris. At ASH, Regeneron reported data from an exploratory cohort testing the two drugs against Ultomiris. Results showed the Regeneron drug combo helped patients achieve and maintain greater control over their disease compared to Ultomiris. Public domain image by Flickr user SciTechTrend