UPCC 10219: Phase II Study Of Stromal Changes Detected By DCE- and DW-MRI In Response To PEGPH20 Combined With Chemotherapy In Subjects With Locally-Advanced Pancreatic Cancer

This research study is being conducted to determine the effects of PEGPH20 plus chemotherapy treatment on the MRI characteristics of locally advanced pancreatic cancer patient tumors. Subjects will received Gemcitabine, Abraxane and PEGPH20.

开始日期2020-01-01

申办/合作机构

Abramson Cancer Center

[+1]

NCT03979066

/ Terminated临床2期IIT

A Phase 2, Open-Label, Multicenter, Randomized Study Evaluating NEOadjuvant Immunotherapy Based Combinations in Patients With Resectable PANCreatic Ductal Adenocarcinoma

The purpose of this study is to determine if study treatment with atezolizumab and PEGPH20 given before and after surgery, followed by chemotherapy is safe and if it can further increase the immune response against the tumor rather than increase the chance of cure.

开始日期2019-11-01

申办/合作机构

Columbia University

[+2]

NCT03634332

/ Unknown status临床2期IIT

Phase II Study of PEGPH20 and Pembrolizumab (MK-3475) for Patients With Previously Treated Hyaluronan High (HA-High) Metastatic Pancreatic Ductal Adenocarcinoma

This study is the study of the combination of PEGPH20 and Pembrolizumab (MK-3475) for patients with previously treated Hyaluronan High (HA-high) metastatic pancreatic ductal adenocarcinoma. This study is an interventional, unblinded, open label study. Approximately 35 subjects will be enrolled. The trial will require approximately a total of 18 months, including 12 months for enrollment, with an additional 6 months for patient follow-up, data collection and study closure.
Each subject will participate in the trial from the time the subject signs the Informed Consent Form (ICF) through the final contact. After a screening phase of up to 21 days, eligible subjects will receive PEGPH20 beginning with Cycle 1 Day 1, on Days 1, 8 15 of every 3 week-cycles and pembrolizumab beginning on Cycle 1 Day 1 (2-4 hrs after PEGPH20), every 3-week-cycles.
Treatment with PEGPH20 and pembrolizumab will continue until progressive disease (PD), unacceptable adverse events (AEs), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the subject, subject withdraws consent, pregnancy of the subject, noncompliance with trial treatment or procedure requirements, subject receives 35 treatments (approximately 24 months) of pembrolizumab, or administrative reasons requiring cessation of treatment. Subjects who discontinue for reasons other than PD will have post-treatment follow-up for disease status until PD, initiating a non-study cancer treatment, withdrawing consent, or becoming lost to follow-up. All subjects will be followed by telephone for overall survival (OS) until death, withdrawal of consent, or the end of the study.
After the end of treatment, each subject will be followed for 30 days for AE monitoring. Serious adverse events (SAE) and events of clinical interest (ECI) will be collected for 90 days after the end of treatment or for 30 days after the end of treatment if the subject initiates new anticancer therapy, whichever is earlier.

开始日期2019-05-01

申办/合作机构

Pancreatic Cancer Research Team

[+3]

100 项与 Pegvorhyaluronidase alfa 相关的临床结果

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100 项与 Pegvorhyaluronidase alfa 相关的转化医学

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100 项与 Pegvorhyaluronidase alfa 相关的专利（医药）

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项与 Pegvorhyaluronidase alfa 相关的文献（医药）

2025-04-01·CLINICAL PHARMACOLOGY & THERAPEUTICS

Investigational Use of Real‐World Data as a Hybrid Control in Pancreatic Ductal Adenocarcinoma From the Randomized Phase Ib/II MORPHEUS Trial

Article

作者: Ponz‐Sarvise, Mariano ; Reyes‐Rivera, Irmarie ; Ci, Bo ; Lau, Janet ; Bretscher, Michael T. ; Oh, Do‐Youn ; Zhu, Jiawen ; Machado, Robson ; Li, Shi ; Patel, Jilpa ; Zhang, Xiaosong ; Ko, Andrew H. ; Psioda, Matthew A. ; Mhatre, Shivani K.

Enrolling adequate numbers of patients into the control arm of randomized controlled trials (RCTs) often presents barriers. There is interest in leveraging real‐world data (RWD) from electronic health records (EHRs) to construct external control (EC) arms to supplement RCT control arms and form hybrid control (HC) arms. This investigation showed the use of an HC arm in second‐line metastatic pancreatic ductal adenocarcinoma (PDAC). The RCT experimental arm (atezolizumab + PEGylated recombinant human hyaluronidase (Atezo + PEGPH20)) was compared with an HC arm consisting of patients treated with modified FOLFOX6 or gemcitabine/nab‐paclitaxel from the MORPHEUS PDAC internal control arm supplemented with data from a nationwide EHR‐derived de‐identified database as the EC arm. The EC arm was constructed by applying key inclusion/exclusion criteria from the MORPHEUS PDAC trial to patients from the real‐world cohort. Baseline variables were balanced using propensity score matching and covariate adjustment. Three analysis approaches—Cox model with pooled‐control data, Cox model with control arm‐specific frailty, and Bayesian analysis using a commensurate prior—were assessed. Overall survival was similar between the treatment arms. The direction and magnitude of hazard ratios (HRs) from the multiple HC analyses (HRs ranged from 1.02 to 1.06) were comparable with the reported trial HR (HR 0.91; 95% CI: 0.56, 1.49). This analysis demonstrates the feasibility and applicability of leveraging RWD in clinical trial design to supplement clinical trial control arms.

2024-12-02·MOLECULAR PHARMACEUTICS

Pathophysiology-Driven Approaches for Overcoming Nanomedicine Resistance in Pancreatic Cancer

Review

作者: Sithara, MS ; Abhi, C ; Mangalanandan, T S ; Unni, Ashok R. ; Nair, Sreejith Thrivikraman ; Kamalasanan, Kaladhar ; Sarma, Manjit ; Pavithran, K.

Tumor heterogeneity poses a significant challenge in cancer therapy. To address this, we analyze pharmacotherapeutic challenges by categorizing them into static and dynamic barriers, reframing these challenges to improve drug delivery, efficacy, and the development of controlled-release nanomedicines (CRNMs). This pathophysiology-driven approach facilitates the design of novel therapeutics tailored to overcome obstacles in pancreatic ductal adenocarcinoma (PDAC) using nanotechnology. Advanced biomaterials in nanodrug delivery systems offer innovative solutions by combining controlled release, stimuli sensitivity, and smart design strategies. CRNMs are engineered to modulate spatiotemporal signaling and control drug release in PDAC, where resistance to conventional therapies is particularly high. This review explores pharmacokinetic considerations for nanomedicine design, RNA interference (RNAi) for stromal modulation, and the development of targeted nanomedicine strategies. Additionally, we highlight the limitations of current animal models in capturing the complexities of PDAC and discuss notable clinical failures, such as PEGylated hyaluronidase (Phase III HALO 109-301 trial) and evofosfamide (TH-302) with gemcitabine (MAESTRO trial), underscoring the need for improved models and treatment strategies. By targeting pathways like Notch and Hedgehog and incorporating stimuli-sensitive and pathway-modulating agents, CRNMs offer a promising avenue to enhance drug penetration and efficacy, reshaping the paradigm of pancreatic cancer treatment.

2024-09-01·BIOMEDICINE & PHARMACOTHERAPY

Hyaluronidase improves the efficacy of nab-paclitaxel after prolonged angiogenesis inhibition in preclinical models for esophagogastric cancer

Article

作者: Liu, Dajia ; Waasdorp, Cynthia ; Meijer, Sybren L ; Oyarce, Cesar ; Bootsma, Sanne ; Guo, Lihui ; Bijlsma, Maarten F ; van Laarhoven, Hanneke W M

BACKGROUND:

Long-term anti-angiogenesis leads to pruned vasculature, densely deposited extracellular matrix (ECM), and consequently reduced chemotherapy delivery in esophagogastric cancer (EGC). To address this issue, we evaluated the efficacy of adding a hyaluronidase or a NO-donor to the regimen of chemotherapy and anti-angiogenic drugs.

METHODS:

A patient-derived EGC xenograft model was developed. Grafted mice were randomly assigned to four experimental groups and one control group. The experimental groups received DC101, a murine angiogenesis inhibitor, and nab-paclitaxel (NPTX), with the addition of hyaluronidase (PEGPH20), or NO-donor (nitroglycerine, NTG), or their combination, respectively. We compared tumor growth during 17 days of treatment. We performed immunohistochemistry for ECM components hyaluronan (HA) and collagen, CD31 for endothelial cells, and γH2AX for DNA damage. The positively stained areas were quantified, and vessel diameters were measured using QuPath software.

RESULTS:

Prolonged DC101 treatment induced deposition of HA (p<0.01) and collagen (p<0.01). HA was effectively degraded by PEGPH20 (p<0.001), but not by NTG as expected. Both PEGPH20 (p<0.05) and NTG (p<0.01) dilated vessels collapsed in response to long-term DC101 treatment. However, only PEGPH20 (rather than NTG) was found to significantly inhibit tumor growth (p<0.05) in combination with NPTX and DC101.

CONCLUSIONS:

These findings suggest that the mechanical barrier of HA is the major reason responsible for the resistance developed during prolonged anti-angiogenesis in EGC. Incorporating PEGPH20 into the existing treatment regimen is promising to improve outcomes for patients with EGC.

项与 Pegvorhyaluronidase alfa 相关的新闻（医药）

2024-11-23

·药智网

默沙东开辟“新战场”

MNC为了对冲重磅产品的销售峰值可以有多拼？别人拼不拼不知道，但当今药王的拥有者默沙东是拼了。K药的核心专利将于2028年到期，为了延缓K药的专利悬崖，默沙东先是All in了“IO+ADC”组合布局，花费大价钱引进第一三共、科伦博泰ADC管线，近期又为了抵御PD-(L)1/VEGF双抗的迭代，耗费不菲的资金拿下礼新医药PD-1/VEGF双抗权益。如今，默沙东又为K药开辟了“新战场”。近日，默沙东宣布皮下注射剂MK-3475A治疗转移性非小细胞肺癌（NSCLC）关键性三期MK-3475A-D77的结果，与静脉注射剂K药相比，MK-3475A治疗组达到药代动力学终点上的非劣性，并在未来公布更全面的数据与监管机构共享，预计该试验将支持所有实体瘤的适应症。 “卷剂型”并不是只有K药一家的策略，在K药之前，罗氏的T药（阿替利珠单抗）皮下注射剂型便获得FDA批准。除此之外，BMS、恒瑞医药、百济神州、君实生物等PD-(L)1玩家均有对此布局。而这也不是PD-(L)1独有的现象，近日第一三共与韩国生物技术公司Alteogen合作，开发Enhertu的皮下注射版本。那么，皮下注射剂型到底有何魅力之处？ <01> 皮下注射的知识点皮下注射的优点显而易见，主要围绕患者依从性和延长产品专利期两个方面： 1）对比传统静脉注射剂型，皮下注射制剂作为一种即用型制剂，在注射时间、患者依从性等层面存在显著优势。比如静脉输注剂型一般需要的30-90分钟，而PD-(L)1皮下注射制剂2-7分钟内即可完成给药，极大缩短了过往静脉注射的给药时间； 2）开发皮下注射剂型能够有效延长药物专利，以罗氏CD20利妥昔单抗为例，该药物在2018产品专利到期，2017年其开发了利妥昔单抗和透明质酸酶的组合物（利妥昔Hycela），新剂型只需要5-7分钟完成皮下注射，而利妥昔Hycela专利保护期至少延长至2030年；从静脉注射到皮下注射，具体的难点是如何实施的呢？皮下注射制剂开发的关键难点是给药体积限制所带来的挑战，由于要考虑注射速度、注射部位、个体患者特征（疼痛感觉敏感性）等多方面因素，通常皮下给药最大注射量约为1-2 mL（以1.5ml以内最佳），要想和静脉注射制剂达到相同的给药剂量就往往需要制备高浓度的蛋白制剂，而高浓度蛋白溶液则往往会带来稳定性差、高粘度、蛋白溶解度、蛋白降解和聚集等问题。目前主流的皮下制剂所用到的一种物质——透明质酸酶，治疗性抗体与透明质酸酶的复方制剂能够在几分钟内给予大体积、高剂量的生物制剂来解决难以开发成高浓度制剂的难题。透明质酸酶，不仅可以显著增加皮下给药的最大注射量，同时可以采用局部注射的方式对透明质酸进行水解，从而降低细胞间质粘性，实现顺利给药。透明质酸存在于人体皮下间隙，作为液体流动的一个屏障，透明质酸酶可通过在注射部位局部暂时清除该屏障，药物可进入皮下间隙并分散，24小时之内透明质酸即可在皮肤下恢复。目前，已经有多款含透明质酸酶的生物制剂获得上市批准，其中不乏有因皮下注射剂型的上市而加速产品放量的品种。图片来源：Biologics CMC <02> 皮下注射“卖水人”Halozyme 起源于圣地亚哥的Halozyme公司，其旗下的ENHANZE技术平台被投资者、媒体称之为“专利提款机”。早在1940年开始，动物源PH20透明质酸酶已被用于增加其他注射药物或液体的吸收和分散。Halozyme公司的ENHANZE技术平台核心是一种专有的重组人透明质酸酶（rHuPH20），rHuPH20是通过基因重组技术人工合成的人源性透明质酸酶，解决了过往动物源性透明质酸酶制剂导致人过敏反应的问题。在rHuPH20成为“专利提款机”之前，Halozyme公司也曾遭遇过大的挫折，其将聚乙二醇化的rHuPH20（PEGPH20）的适应症布局扩展到了胰腺癌，其设计逻辑是将PEGPH20作用于肿瘤微环境，用于破坏致密肿瘤组织中的透明质酸，使化疗药物更容易进入。2019年，Halozyme宣布PEGPH20在一项针对胰腺癌的3期HALO-301试验中未能达到主要终点，PEGPH20联合吉西他滨、白蛋白结合型紫杉醇治疗组相比单独使用吉西他滨、白蛋白结合型紫杉醇对照组mOS未见明显改善。经历挫折重整后，Halozyme公司快速调整战略，利用专有的ENHANZE技术平台优势赋能合作伙伴，在收取授权费用的同时，以在合作开发管线达到里程碑或上市后收取源源不断的分成费用。公司收入角度来看，Halozyme从2014年开始产生特许权使用费收入，2021年以前一直徘徊在1亿美元以内，而2021-2023年公司此项收入为2.04亿美元、3.6亿美元和4.48亿美元，呈现逐年稳步上升的态势。从下表也可以看出，与Halozyme合作并成功推动产品上市的有多家巨头，包括罗氏、强生、武田、Teva等，合作的产品包括前面提到的T药皮下注射版、达雷妥尤单抗皮下注射版、利妥昔单抗皮下注射版等等。图片来源：瞪羚社 Halozyme能够取得如此迅猛的业绩成长，很大程度是与“强生大哥”达雷妥尤单抗的相互成就，2019-2023年其销售分别为29.98亿美元、41.9亿美元、60.23亿美元、79.77亿美元和97.44亿美元（达雷妥尤单抗皮下注射剂型2020年上市）。据Halozyme和强生的口径，达雷妥尤单抗取得迅猛增长，皮下注射剂型（DARZALEX FASPRO）的上市功不可没，其在上市后迅速被市场接受，市场份额不断攀升。据强生在2022年中的一场电话会上表示，在美国、欧洲市场，达雷妥尤静脉注射到皮下注射的转换率分别达到了85%、80%。尽管达雷妥尤单抗的专利在2026年到期，Halozyme合作管线中仍有重磅炸弹潜力产品，如Argenx的艾加莫德，有望对冲收入下降的风向。 <03> 潜力药物通过皮下注射取得优势展望未来，可以预见不少重磅药物可能通过率先开发皮下注射剂型取得市场优势。海外潜在重磅炸弹中，最典型的案例莫过于强生的埃万妥单抗，近日公布的PALOMA-3试验结果显示（418位接受奥希替尼和铂类化疗治疗后或期间出现进展的EGFR突变晚期NSCLC患者），接受皮下和静脉组的ORR分别为30%和33%，中位PFS分别为6.1和4.3个月。同时皮下组与静脉组相比，OS更长，较少患者出现输注相关反应（13%vs 66%）和静脉血栓栓塞（9%vs 14%）。皮下注射版埃万妥单抗不仅在剂型上对静脉版埃万妥单抗取得优势，PALOMA-3数据表明皮下注射版埃万妥单抗同样具备疗效和安全性上的优势，这为其日后冲击NSCLC一线治疗增添了筹码。回溯国内，康宁杰瑞/思路迪2021年11月上市的恩沃利单抗也是一个典型的案例，该药物是全球首款皮下注射PD-L1单抗，其具备常温下稳定、注射部位限制少、皮下注射给药便捷等优势。2022-2023年恩沃利单抗销售为5.67亿元、6.349亿元，作为国产第6款PD-(L)1药物，能够在内卷的环境下第一年取得如此商业化成绩，除了其获批的适应症微卫星高度不稳定（MSI-H）或错配修复基因缺陷型（dMMR）不限瘤种的特殊性外，皮下注射剂型的优势功不可没。国内不乏有大胆尝试的Biotech，一旦做出来便能取得“王炸”效果。比如来凯医药，其率先在自主研发的LAE102的一期临床设计中加入皮下注射的给药方式，一方面其作为“减脂增肌”药物方便与GLP-1联用，另一方面也能够对比其与静脉注射的优劣，而全球ActRIIA这类靶点药物给药采用皮下注射，来凯医药还是第一家，若能够取得良好结果，那么很可能是差异化的同类首创。另一个案例是康宁杰瑞，其率先试验HER2双抗ADC与PD-L1抑制剂组成的高浓度皮下注射复方制剂JSKN033，其首次人体临床数据入选了2024 SITC，是IO+ADC首次皮下注射的全新尝试。该数据显示：10例疗效可评估患者中，3例患者出现部分缓解，5例患者疾病稳定，疾病控制率（DCR）达80%；安全性方面，最常见的治疗相关不良事件是1级注射部位反应，同时未观察到剂量限制性毒性。结语：K药皮下注射剂型的成功，给一众Biotech甚至MNC打开了全新的思路，一个小小的剂型改变，其带来的差异化优势有时候无可估量。日后，Biotech们在抗体药物开发层面大概率会更加重视皮下剂型，从而潜移默化实现肿瘤、自免药物的给药方式的变革。来源 | 瞪羚社（药智网获取授权转载）撰稿 | Kris. 责任编辑 | 八角声明：本文系药智网转载内容，图片、文字版权归原作者所有，转载目的在于传递更多信息，并不代表本平台观点。如涉及作品内容、版权和其它问题，请在本平台留言，我们将在第一时间删除。商务合作 | 王存星 19922864877（同微信）阅读原文，是受欢迎的文章哦

专利到期抗体药物偶联物临床3期

2024-11-21

·同写意

药王放了个大

此次医博会由同写意策划，以“发展新质生产力，共享健康新未来”为主题，用全新的视角瞄准国内外医药及大健康产业发展前沿。诚邀海内外医药及大健康各界嘉宾齐聚中国医药城，共赴时代之约。 MNC为了对冲重磅产品的销售峰值可以有多拼？别人拼不拼不知道，但当今药王的拥有者默沙东是拼了。K药的核心专利将于2028年到期，为了延缓K药的专利悬崖，默沙东先是All in了“IO+ADC”组合布局，花费大价钱引进第一三共、科伦博泰ADC管线，近期又为了抵御PD-(L)1/VEGF双抗的迭代，耗费不菲的资金拿下礼新医药PD-1/VEGF双抗权益。如今，默沙东又为K药开辟了“新战场”。11月19日，默沙东宣布皮下注射剂MK-3475A治疗转移性非小细胞肺癌（NSCLC）关键性三期MK-3475A-D77的结果，与静脉注射剂K药相比，MK-3475A治疗组达到药代动力学终点上的非劣性，并在未来公布更全面的数据与监管机构共享，预计该试验将支持所有实体瘤的适应症。 “卷剂型”并不是只有K药一家的策略，在K药之前，罗氏的T药（阿替利珠单抗）皮下注射剂型便获得FDA批准。除此之外，BMS、恒瑞医药、百济神州、君实生物等PD-(L)1玩家均有对此布局。而这也不是PD-(L)1独有的现象，近日第一三共与韩国生物技术公司Alteogen合作，开发Enhertu的皮下注射版本。那么，皮下注射剂型到底有何魅力之处？ 1 皮下注射的知识点皮下注射的优点显而易见，主要围绕患者依从性和延长产品专利期两个方面： 1）对比传统静脉注射剂型，皮下注射制剂作为一种即用型制剂，在注射时间、患者依从性等层面存在显著优势。比如静脉输注剂型一般需要的30-90分钟，而PD-(L)1皮下注射制剂2-7分钟内即可完成给药，极大缩短了过往静脉注射的给药时间； 2）开发皮下注射剂型能够有效延长药物专利，以罗氏CD20利妥昔单抗为例，该药物在2018产品专利到期，2017年其开发了利妥昔单抗和透明质酸酶的组合物（利妥昔Hycela），新剂型只需要5-7分钟完成皮下注射，而利妥昔Hycela专利保护期至少延长至2030年；从静脉注射到皮下注射，具体的难点是如何实施的呢？皮下注射制剂开发的关键难点是给药体积限制所带来的挑战，由于要考虑注射速度、注射部位、个体患者特征（疼痛感觉敏感性）等多方面因素，通常皮下给药最大注射量约为1-2 mL（以1.5ml以内最佳），要想和静脉注射制剂达到相同的给药剂量就往往需要制备高浓度的蛋白制剂，而高浓度蛋白溶液则往往会带来稳定性差、高粘度、蛋白溶解度、蛋白降解和聚集等问题。目前主流的皮下制剂所用到的一种物质——透明质酸酶，治疗性抗体与透明质酸酶的复方制剂能够在几分钟内给予大体积、高剂量的生物制剂来解决难以开发成高浓度制剂的难题。（图源：上海艾伟拓医药）透明质酸酶，不仅可以显著增加皮下给药的最大注射量，同时可以采用局部注射的方式对透明质酸进行水解，从而降低细胞间质粘性，实现顺利给药。透明质酸存在于人体皮下间隙，作为液体流动的一个屏障，透明质酸酶可通过在注射部位局部暂时清除该屏障，药物可进入皮下间隙并分散，24小时之内透明质酸即可在皮肤下恢复。目前，已经有多款含透明质酸酶的生物制剂获得上市批准，其中不乏有因皮下注射剂型的上市而加速产品放量的品种。（图源：Biologics CMC） 2 皮下注射“卖水人”Halozyme 起源于圣地亚哥的Halozyme公司，其旗下的ENHANZE技术平台被投资者、媒体称之为“专利提款机”。早在1940年开始，动物源PH20透明质酸酶已被用于增加其他注射药物或液体的吸收和分散。Halozyme公司的ENHANZE技术平台核心是一种专有的重组人透明质酸酶（rHuPH20），rHuPH20是通过基因重组技术人工合成的人源性透明质酸酶，解决了过往动物源性透明质酸酶制剂导致人过敏反应的问题。在rHuPH20成为“专利提款机”之前，Halozyme公司也曾遭遇过大的挫折，其将聚乙二醇化的rHuPH20（PEGPH20）的适应症布局扩展到了胰腺癌，其设计逻辑是将PEGPH20作用于肿瘤微环境，用于破坏致密肿瘤组织中的透明质酸，使化疗药物更容易进入。2019年，Halozyme宣布PEGPH20在一项针对胰腺癌的3期HALO-301试验中未能达到主要终点，PEGPH20联合吉西他滨、白蛋白结合型紫杉醇治疗组相比单独使用吉西他滨、白蛋白结合型紫杉醇对照组mOS未见明显改善。经历挫折重整后，Halozyme公司快速调整战略，利用专有的ENHANZE技术平台优势赋能合作伙伴，在收取授权费用的同时，以在合作开发管线达到里程碑或上市后收取源源不断的分成费用。公司收入角度来看，Halozyme从2014年开始产生特许权使用费收入，2021年以前一直徘徊在1亿美元以内，而2021-2023年公司此项收入为2.04亿美元、3.6亿美元和4.48亿美元，呈现逐年稳步上升的态势。从下表也可以看出，与Halozyme合作并成功推动产品上市的有多家巨头，包括罗氏、强生、武田、Teva等，合作的产品包括前面提到的T药皮下注射版、达雷妥尤单抗皮下注射版、利妥昔单抗皮下注射版等等。 Halozyme能够取得如此迅猛的业绩成长，很大程度是与“强生大哥”达雷妥尤单抗的相互成就，2019-2023年其销售分别为29.98亿美元、41.9亿美元、60.23亿美元、79.77亿美元和97.44亿美元（达雷妥尤单抗皮下注射剂型2020年上市）。据Halozyme和强生的口径，达雷妥尤单抗取得迅猛增长，皮下注射剂型（DARZALEX FASPRO）的上市功不可没，其在上市后迅速被市场接受，市场份额不断攀升。据强生在2022年中的一场电话会上表示，在美国、欧洲市场，达雷妥尤静脉注射到皮下注射的转换率分别达到了85%、80%。尽管达雷妥尤单抗的专利在2026年到期，Halozyme合作管线中仍有重磅炸弹潜力产品，如Argenx的艾加莫德，有望对冲收入下降的风向。 3 潜力药物通过皮下注射取得优势展望未来，可以预见不少重磅药物可能通过率先开发皮下注射剂型取得市场优势。海外潜在重磅炸弹中，最典型的案例莫过于强生的埃万妥单抗，近日公布的PALOMA-3试验结果显示（418位接受奥希替尼和铂类化疗治疗后或期间出现进展的EGFR突变晚期NSCLC患者），接受皮下和静脉组的ORR分别为30%和33%，中位PFS分别为6.1和4.3个月。同时皮下组与静脉组相比，OS更长，较少患者出现输注相关反应（13% vs 66%）和静脉血栓栓塞（9% vs 14%）。皮下注射版埃万妥单抗不仅在剂型上对静脉版埃万妥单抗取得优势，PALOMA-3数据表明皮下注射版埃万妥单抗同样具备疗效和安全性上的优势，这为其日后冲击NSCLC一线治疗增添了筹码。回溯国内，康宁杰瑞/思路迪2021年11月上市的恩沃利单抗也是一个典型的案例，该药物是全球首款皮下注射PD-L1单抗，其具备常温下稳定、注射部位限制少、皮下注射给药便捷等优势。2022-2023年恩沃利单抗销售为5.67亿元、6.349亿元，作为国产第6款PD-(L)1药物，能够在内卷的环境下第一年取得如此商业化成绩，除了其获批的适应症微卫星高度不稳定（MSI-H）或错配修复基因缺陷型（dMMR）不限瘤种的特殊性外，皮下注射剂型的优势功不可没。国内不乏有大胆尝试的Biotech，一旦做出来便能取得“王炸”效果。比如来凯医药，其率先在自主研发的LAE102的一期临床设计中加入皮下注射的给药方式，一方面其作为“减脂增肌”药物方便与GLP-1联用，另一方面也能够对比其与静脉注射的优劣，而全球ActRIIA这类靶点药物给药采用皮下注射，来凯医药还是第一家，若能够取得良好结果，那么很可能是差异化的同类首创。另一个案例是康宁杰瑞，其率先试验HER2双抗ADC与PD-L1抑制剂组成的高浓度皮下注射复方制剂JSKN033，其首次人体临床数据入选了2024 SITC，是IO+ADC首次皮下注射的全新尝试。该数据显示：10例疗效可评估患者中，3例患者出现部分缓解，5例患者疾病稳定，疾病控制率（DCR）达80%；安全性方面，最常见的治疗相关不良事件是1级注射部位反应，同时未观察到剂量限制性毒性。结语：K药皮下注射剂型的成功，给一众Biotech甚至MNC打开了全新的思路，一个小小的剂型改变，其带来的差异化优势有时候无可估量。日后，Biotech们在抗体药物开发层面大概率会更加重视皮下剂型，从而潜移默化实现肿瘤、自免药物的给药方式的变革。同写意媒体矩阵，欢迎关注↓↓↓

专利到期抗体药物偶联物

2023-09-08

·PMLiVE

ICR study finds way to determine efficacy of experimental breast cancer drugs

Researchers at The Institute of Cancer Research (ICR), London, have discovered a way to use a simple, non-invasive MRI scan to determine whether an experimental approach to enhance treatment for breast cancer is effective. New research from the study, funded by Cancer Research UK, could help doctors visualise tumours and speed up the development of targeted therapies for breast cancer. If successful, these drugs could enhance the effectiveness of other drugs administered in combination. Common features of breast cancer include excessive connective tissue, which consists of cells and fibres that provide a scaffold, known as the extracellular matrix (ECM), where tumours can grow. Hyaluronic acid, which works by absorbing water, is naturally present inside the tumour ECM and causes cancer tumours to swell, making it challenging for drugs to penetrate, reach and destroy cancer cells. Researchers are able to use experimental drugs that target and degrade a chemical called hyaluronic acid to dissolve some of the dense ECM and improve drug delivery to tumours. However, when using experimental drugs targeting the chemical in this way, it can be difficult for researchers to identify the exact time when the acid has been degraded, and therefore, it is a challenge to determine the best time to administer other drugs. The researchers performed multi-parametric MRI scans on mice with breast tumours to track the efforts of PEGPH20, an investigational drug targeting hyaluronic acid, to gain measurements that provide additional information about the tissue being analysed. Study leader, Simon Robinson, professor, magnetic resonance imaging of cancer, ICR, London, said: "Diffusion-weighted MRI can be performed on conventional clinical MRI scanners. Our new research shows that we can use such scans to check if [experimental] drugs like PEGPH20 are working, helping guide treatment in a more targeted and non-invasive way." For example, after using diffusion-weighted imaging to understand how water molecules moved within tissue, the researchers found that a measurement of water’s ability to move or spread, called the apparent diffusion coefficient (ADC), was reduced by up to 38% following administration of PEGPH20. The results suggest that PEGPH20 could make breast cancer tissue more accessible to chemotherapy drugs and could potentially improve treatment outcomes. Upon further necessary testing, the researchers hope to improve the development of targeted therapies for breast cancer and potentially other tumours.

100 项与 Pegvorhyaluronidase alfa 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11201	-	-	DB14912

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
胰腺导管腺癌	临床3期	美国	Halozyme Therapeutics, Inc.	2016-03-14
胰腺导管腺癌	临床3期	澳大利亚	Halozyme Therapeutics, Inc.	2016-03-14
胰腺导管腺癌	临床3期	比利时	Halozyme Therapeutics, Inc.	2016-03-14
胰腺导管腺癌	临床3期	巴西	Halozyme Therapeutics, Inc.	2016-03-14
胰腺导管腺癌	临床3期	加拿大	Halozyme Therapeutics, Inc.	2016-03-14
胰腺导管腺癌	临床3期	克罗地亚	Halozyme Therapeutics, Inc.	2016-03-14
胰腺导管腺癌	临床3期	捷克	Halozyme Therapeutics, Inc.	2016-03-14
胰腺导管腺癌	临床3期	丹麦	Halozyme Therapeutics, Inc.	2016-03-14
胰腺导管腺癌	临床3期	爱沙尼亚	Halozyme Therapeutics, Inc.	2016-03-14
胰腺导管腺癌	临床3期	法国	Halozyme Therapeutics, Inc.	2016-03-14

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


EASD2022	N/A	肾小球疾病 HA \| CD44 +	-	PEGPH20	鹽夢淵壓積鏇餘選製壓(網鹽鑰醖構夢遞鬱夢鏇) = 壓遞衊鑰獵製鹹繭顧醖簾鹹築壓憲衊選糧顧繭 (遞憲簾衊製鏇鬱網鹹壓 ) 更多	积极	2022-09-22
				Vehicle	鹽夢淵壓積鏇餘選製壓(網鹽鑰醖構夢遞鬱夢鏇) = 鏇築窪夢築廠壓構廠遞簾鹹築壓憲衊選糧顧繭 (遞憲簾衊製鏇鬱網鹹壓 ) 更多
NCT01839487 (HALO109-202, Pubmed \| J Transl Med)	临床2期	转移性胰腺导管腺癌	279	Pegvorhyaluronidase alfa plus nab-paclitaxel/gemcitabine	獵夢醖範製顧鹹繭顧膚(淵壓願膚蓋觸顧觸顧艱) = 繭範衊築築襯鹹壓積衊範繭網選簾築鹹鏇膚築 (艱窪網製膚鏇憲衊壓網 ) 更多	积极	2021-01-21
				Nab-paclitaxel/gemcitabine	獵夢醖範製顧鹹繭顧膚(淵壓願膚蓋觸顧觸顧艱) = 簾網願網獵簾選獵艱願範繭網選簾築鹹鏇膚築 (艱窪網製膚鏇憲衊壓網 ) 更多
NCT03979066 (NEOiPANC, CTgov)	临床2期	胰腺导管腺癌	1	atezolizumab (Atezolizumab)	簾積淵願醖築觸鑰簾齋(窪鬱糧構遞積憲鑰壓醖) = 構憲壓鏇餘繭遞遞觸壓鏇鹹繭衊壓鹽艱鹹顧範 (窪膚糧簾餘獵簾鑰憲膚, 顧製繭艱壓繭艱簾鏇觸 ~ 壓衊鑰遞簾淵觸構願遞) 更多	-	2020-12-23
				atezolizumab+PEGPH20 (Atezolizumab in Combination With PEGPH20)	簾積淵願醖築觸鑰簾齋(窪鬱糧構遞積憲鑰壓醖) = 衊鹹築衊膚艱繭廠廠繭鏇鹹繭衊壓鹽艱鹹顧範 (窪膚糧簾餘獵簾鑰憲膚, 觸淵選鹽鏇糧夢選淵觸 ~ 遞鏇繭齋範簾鹽網醖簾) 更多
NCT02715804 (HALO 109-301, Pubmed \| J Urol) 人工标引	临床3期	转移性胰腺腺癌一线	492	Nab-Paclitaxel+Gemcitabine+Pegvorhyaluronidase Alfa	獵夢鏇餘蓋糧觸鬱網繭(鹹鬱餘網壓膚糧構獵鑰) = 蓋獵衊蓋繭衊膚憲鑰鹹觸襯窪願顧餘製遞網餘 (餘鏇範淵淵鏇壓鑰鹹範 ) 更多	不佳	2020-09-20
				Nab-Paclitaxel+Gemcitabine+Placebo	獵夢鏇餘蓋糧觸鬱網繭(鹹鬱餘網壓膚糧構獵鑰) = 襯膚艱顧壓艱鏇顧蓋膚觸襯窪願顧餘製遞網餘 (餘鏇範淵淵鏇壓鑰鹹範 ) 更多
NCT02715804 (HALO 109-301, CTgov)	临床3期	胰腺导管腺癌	492	nab-Paclitaxel+Gemcitabine+PEGPH20 (PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine)	獵簾淵製鹽構窪積築選(觸繭鏇廠糧齋鹽夢遞淵) = 範鬱壓構範齋鑰齋鹹艱鑰積網蓋鏇憲構糧構蓋 (壓衊壓遞醖鏇窪齋構鬱, 鏇鬱蓋壓選壓餘積餘艱 ~ 鹽糧餘夢獵齋夢築鬱廠) 更多	-	2020-07-14
				Placebo+nab-Paclitaxel+Gemcitabine (AG: Placebo + Nab-Paclitaxel + Gemcitabine)	獵簾淵製鹽構窪積築選(觸繭鏇廠糧齋鹽夢遞淵) = 鹽網鏇鏇夢艱觸築簾鬱鑰積網蓋鏇憲構糧構蓋 (壓衊壓遞醖鏇窪齋構鬱, 鏇鹽觸廠獵齋鏇選廠淵 ~ 鹽醖餘簾構網願齋窪鹽) 更多
NCT03193190 \| NCT03281369 (ASCO 12020 \| ASCO 22020) 人工标引	临床1/2期	胰腺导管腺癌 \| 胃癌二线	133	atezolizumab+PEGPH20 (M-PDAC)	鹽獵鹽鹹鬱簾齋鏇醖鑰(構構繭觸衊夢繭餘製選) = 願淵獵獵憲鏇糧繭窪夢廠淵齋選襯憲選蓋鹹範 (製淵醖築網觸範窪衊願 ) 更多	不佳	2020-05-25
				mFOLFOX6 or gemcitabine + nab-paclitaxel (M-PDAC)	鹽獵鹽鹹鬱簾齋鏇醖鑰(構構繭觸衊夢繭餘製選) = 選製觸憲鬱憲積製窪構廠淵齋選襯憲選蓋鹹範 (製淵醖築網觸範窪衊願 ) 更多
NCT01959139 (SWOG S1313 \| S1313, CTgov)	临床1/2期	转移性胰腺腺癌 \| 转移性胰腺癌	126	Leucovorin+Irinotecan+Oxaliplatin+5-fluorouracil (Phase II: mFOLFIRINOX)	範憲壓鑰選獵獵簾鹽膚(鏇齋製製壓襯衊衊範蓋) = 網積憲繭襯網夢蓋鬱獵蓋艱壓築遞築鹽醖築構 (餘獵膚構鏇膚鑰艱鹽鏇, 壓齋鏇網觸製範醖築觸 ~ 鑰淵蓋選餘網鹹窪憲襯) 更多	-	2020-02-12
				Leucovorin+Irinotecan+Oxaliplatin+PEGPH20+5-fluorouracil (Phase II: mFOLFIRINOX + PEGPH20)	範憲壓鑰選獵獵簾鹽膚(鏇齋製製壓襯衊衊範蓋) = 構壓顧淵蓋範範糧顧鹽蓋艱壓築遞築鹽醖築構 (餘獵膚構鏇膚鑰艱鹽鏇, 醖淵艱齋廠構觸餘廠鹹 ~ 製選齋壓壓願觸齋鏇觸) 更多
NCT03267940 (CTgov)	临床1期	肝内胆管癌 \| 不可切除的肝内胆管癌 \| 胆囊腺癌	85	GEM+CIS+PEGPH20 (Run-in Portion: PEGCISGEM)	選範醖網積膚鬱醖淵願 = 選簾遞淵鑰鹹糧範顧淵遞憲鏇壓願餘獵膚鑰憲 (餘襯顧膚鬱襯憲觸築膚, 範餘範觸製膚網襯糧鏇 ~ 鏇餘獵蓋襯艱廠鏇簾鹽) 更多	-	2020-02-07
				GEM+atezolizumab+CIS+PEGPH20 (Run-in Portion: PEGCISGEMATEZO)	選範醖網積膚鬱醖淵願 = 網遞淵顧襯觸網淵築淵遞憲鏇壓願餘獵膚鑰憲 (餘襯顧膚鬱襯憲觸築膚, 製獵鹹窪製構獵餘齋餘 ~ 願積構顧積窪積築網顧) 更多
NCT02715804 (HALO 109-301, ASCO_GI2020)	临床3期	转移性胰腺导管腺癌	494	PEGPH20 + nab-paclitaxel/gemcitabine	壓齋窪觸網餘鹹糧築網(繭鑰鹹鑰廠醖襯鑰鏇繭) = neutropenia (44% vs 47%), thrombocytopenia (21% vs 16%) and fatigue (16% vs 10%); G3+ rates were 6% vs 7% for TE events, 5% vs 2% for bleeding events and 13% vs 5% for musculoskeletal events. 餘蓋範觸構衊積醖鑰鹹 (願選繭鹽廠襯鬱範艱鏇 ) 更多	不佳	2020-02-04
				Placebo + nab-paclitaxel/gemcitabine