Atezolizumab/Hyaluronidase-tqjs

Bristol Myers Squibb has won FDA approval for an injectable version of its blockbuster cancer immunotherapy Opdivo, a regulatory decision that gives patients a more convenient dosing option and provides the pharmaceutical giant a new way to fend off coming competition. The pivotal test for injectable Opdivo evaluated the drug in renal cell carcinoma, but the approval announced late Friday spans all of the approved solid tumor indications covered by approvals for intravenously infused Opdivo as a monotherapy. BMS will market the new injectable drug as Opdivo Qvantig. Opdivo belongs to the class of therapies called checkpoint inhibitors. The drug itself is an antibody designed to block PD-1, a checkpoint protein on immune cells that stops them from recognizing cancer cells. First approved in 2014 as a treatment for melanoma, the drug has gone on to win numerous approvals in additional cancers. In the first nine months of 2024, Opdivo, in all of its approved indications, accounted for $6.8 billion in sales. The immunotherapy is BMS’s top-selling cancer product. Health IT Reducing Clinical and Staff Burnout with AI Automation As technology advances, AI-powered tools will increasingly reduce the administrative burdens on healthcare providers. By Dr. Michael Blackman, Chief Medical Officer at Greenway Health Antibody drugs are typically administered as intravenous infusions; dosing of Opdivo takes about 30 minutes. BMS said an injection of Opdivo Qvantig takes three to five minutes. In a Phase 3 test that compared monthly injections of Opdivo Qvantig to every-two-week infusions of Opdivo as a treatment for advanced or metastatic clear cell renal cell carcinoma, results showed the injectable version met the main goal of achieving comparable exposure throughout the body and similar efficacy. Results also showed the new injectable version’s safety profile was comparable to that of Opdivo. Beyond Opdivo Qvantig’s approval in all of the solid tumor indications for Opdivo, the new injectable product is approved as a monotherapy maintenance treatment after a patient has completed treatment with Opdivo plus Yervoy, a different BMS immunotherapy. The injectable version of Opdivo may also be used in combination with chemotherapy or the cancer drug cabozantinib. Opdivo Qvantig is not approved for use in combination with intravenously infused Yervoy. “Over the last decade, Opdivo has evolved as an immunotherapy option used in many indications across tumor types,” Adam Lenkowski, BMS’s executive vice president and chief commercialization officer, said in a prepared statement. “With this new option, we look forward to further helping cancer patients with an administration method that gives them faster delivery.” The faster delivery of Opdivo Qvantig is made possible by Enhanze, a drug delivery technology developed by biotech company Halozyme. Enhanze consists of an engineered enzyme that enables biologic drugs to be administered as subcutaneous injections. The key patent for Opdivo will expire in 2028, opening the door to competition from biosimilar versions of the IV infused drug. Opdivo Qvantig could help BMS retain some of its immunotherapy market share with a patent-protected alternative dosing option. presented by Health IT Transforming Patient Care: The Role of AI-Powered Assistants The progress in artificial intelligence (AI) is reshaping patient care, across various dimensions, from facilitating faster discharge to curating treatment plans and suggesting lifestyle changes. By IT Medical Other pharma giants are also pursuing subcutaneous dosing for their respective checkpoint inhibitors. In September, Roche won FDA approval for Tecentriq Hybreza, the injectable version of its PD-L1 inhibitor Tecentriq. Like Opdivo Qvantig, the Roche immunotherapy is made with Halozyme’s technology. Meanwhile, Merck last month posted positive Phase 3 data for an injectable version of its blockbuster PD-1 inhibitor, Keytruda. Injectable Keytruda employs enzyme technology from Alteogen.

延续十年之久的KO大战，出现了些许变数。 2024年12月28日，FDA批准了BMS的Opdivo皮下注射剂Opdivo Qvantig（nivolumab加透明质酸酶）上市，用于所有已批准的Opdivo适应症。 此次批准，意味着Opdivo成为全球首款获批上市的PD-1皮下制剂。 今年5月，BMS宣布FDA更改了Opdivo皮下制剂的生物制品许可申请（BLA）的PDUFA日期，从2025年2月28日提前至2024年12月29日。 此次Opdivo皮下制剂如期获批，主要基于随机开放标签的III期CheckMate-67T研究（N=495）数据。试验结果表明，Opdivo皮下制剂在药代动力学和反应上显示出与静脉注射Opdivo非劣效性，皮下制剂组ORR为24.2%，而静脉注射组为18.2%。安全性方面，Opdivo皮下制剂与静脉注射版本表现相似，最常见的不良反应包括疲劳、肌肉骨骼疼痛等。 其次，PD-1皮下制剂与传统PD-1/PD-L1抗体相比最大的优势，就是提高便捷性。作为即用型制剂，Opdivo皮下制剂可在3-5分钟内完成给药，而静脉输注剂型则需要30-90分钟，极大缩减了给药时间，提高患者生活质量，节约医疗资源。 Opdivo皮下制剂由Opdivo与Halozyme专有的重组人透明质酸酶PH20（rHuPH20）组成。 通过使用重组透明质酸酶PH20，实现皮下给药是目前较为常见的剂型改变方式，旨在增加皮下给药的最大注射量。 想要实现皮下给药的核心，是提高浓度制剂，这对药物的亲疏水性、稳定性、粘度等有很高要求。而当药物浓度提高到一定限度仍然不能满足给药剂量时，可以考虑采取一些办法增大给药体积。 此时，我们可以通过透明质酸酶在注射部位局部分解透明质酸，帮助大量的液体在皮下间隙并分散，且透明质酸在24小时之内即可在皮肤下恢复。 透明质酸，就是我们常说的玻尿酸。是一种存在于人体组织中的多糖，具有很高的黏度和保水性，可以保持组织的结构和水分。在皮下组织中，透明质酸形成了一个致密的网状结构，它会限制大分子药物的扩散和吸收。 今年9月，FDA批准了罗氏PD-L1抗体Tecentriq的皮下制剂版本Tecentriq Hybreza （Tecentriq和透明质酸酶-TQJS），也是运用此机制。此外通过透明质酸酶也有望开发ADC的皮下制剂，今年11月药时代报道了DS-8201皮下制剂的相关消息。 在过去几十年中，免疫疗法在肿瘤学领域确立了其革命性的地位，PD-（L）1的出现更是改变了癌症治疗的传统模式。 2014年，Opdivo在日本获批上市，成为第一款获批上市的PD-1药物。两个月后，9月，Keytruda率先获得美国FDA批准，成为FDA批准的首款PD-1新药。3个月后，12月22日，Opdivo也获得FDA批准上市。你追我赶之间，KO大战就此展开，也点燃了全球PD-（L）1的研发热潮。 时至今日，人手“一款PD-（L）1”成为业内常态，PD-（L）1也成为了目前全球药企之间最为拥挤的细分市场之一。在此背景下，从“卷”产品到“卷”适应症，从寻求差异化创新到出海，成为了所有PD-（L）1厂家的必经之路。 皮下制剂，便是“卷”剂型的必然结果。此次Opdivo皮下制剂的获批，带领着全球PD-（L）1进入下一站。目前，默沙东的Keytruda、辉瑞的sasanlimab在临床进度上处于全球前列，有望继Opdivo皮下制剂之后相继上市。 国内方面，康宁杰瑞、百济神州、恒瑞医药、君实生物等众多药业也均布局了PD-（L）1皮下制剂的开发。其中，君实生物的特瑞普利单抗皮下制剂临床进展最快，已于今年5月启动三期临床。 可以预见的是，随着此次Opdivo皮下制剂的获批，一场关于皮下剂型的竞逐已升温至白热化阶段。药时代将持续关注。 参考资料： 1.FDA官网 2.3亿美元！第一三共开发DS-8201皮下制剂（药时代文章） 3.PD-1的尽头是皮下注射剂？罗氏、默沙东、BMS、君实……肿瘤免疫市场下一轮开卷（医药经济报） 4.其他公开资料 封面图来源：豆包AI 2024：生物制药行业的这些经典“教训”，给行业提了个醒！ 2024-12-27 国务院开会，指出「罕见病创新药」减免临床试验！ 2024-12-26 药明康德出售WuXi ATU英、美业务，业界看法不一 2024-12-25 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 点击，查看更多精彩!