Metreleptin

关注并星标CPHI制药在线从2025年起至2029年，多款生物制剂将陆续面临专利保护终止的节点，涵盖肿瘤、自身免疫、代谢紊乱及罕见病等多个高价值治疗领域（图1）。这些面临专利悬崖的重要药物不仅在全球药品销售榜上长期占据前列，也在各大跨国药企的收入结构中扮演核心角色。随着专利期的结束，生物类似药的进入将加速重塑市场竞争格局，为仿制药企打开数十亿美元级别的商业机会，同时也迫使原研药企加快布局生命周期管理、差异化竞争与市场准入策略的调整。专利悬崖不仅意味着法律地位的转变，更预示着一个新的竞争周期的开启。　　图1. 2025-2029年部分生物制剂专利到期时间轴。2025年：HER2靶向格局或生变，自免仿制潜力渐显2025年将成为HER2阳性乳腺癌治疗领域的一个转折点。基因泰克的Perjeta（Pertuzumab，帕妥珠单抗，中国商品名：帕捷特）专利即将到期，这款与Herceptin联用的疗法是乳腺癌靶向治疗的重要基石。尽管生物类似药的开发在结构与疗效比对上仍有一定技术门槛，但已有多家公司布局相关管线，预示着HER2靶向治疗未来将走向价格优化与市场细分并行的格局。同样在2025年面临专利悬崖的GSK的Benlysta（belimumab，贝利尤单抗，中国商品名：倍力腾）是系统性红斑狼疮领域的首个生物制剂。其结构相对传统，开发难度较低，因此生物类似药的进入预计将更加迅速，有望打破目前该领域的高价垄断，扩大治疗的可及性。Blincyto（Blinatumomab，贝林妥欧单抗，中文商品名：贝利妥）为Amgen开发的双特异性抗体，用于治疗急性淋巴细胞白血病，其构建机制复杂、剂型特殊，对生物类似药开发提出更高挑战，仿制企业需具备扎实的双抗工艺平台。Elelyso（taliglucerase alfa）则针对戈谢病这一罕见病种，尽管市场规模有限，但在专利到期后，价格的适度下降可能带来治疗的边际人群扩大。2026年：自身免疫与软组织肿瘤治疗面临洗牌2026年，基因泰克的另一款 HER2阳性乳腺癌药物Kadcyla（ado-trastuzumab emtansin）专利即将到期。虽Kadcyla专利保护期将尽，但其作为 ADC模态的药物具有复杂的生产工艺和药代动力学特性，使得仿制门槛依然很高。其潜在生物类似药需在连接子稳定性、毒素释放效率等多个维度实现一致性，预计市场进入将较为谨慎。礼来的Lartruvo（Olaratumab，奥拉鲁单抗）尽管曾获FDA加速批准用于软组织肉瘤，但由于后期研究未达预期已退出市场，其专利到期更多具象征意义。而礼来另一款单抗药物Taltz（Ixekizumab，依奇珠单抗，中文商品名：拓咨）则是礼来在银屑病和银屑病关节炎领域的重要布局产品之一，其结构较为常规。随着IL-17通路药物竞争日趋激烈，Taltz的专利到期可能刺激同类产品价格联动式下调，也为生物类似药打开切入口。2027年：代谢病与罕见病治疗双线释放机会2027年，代谢性疾病治疗将成为焦点。礼来的Trulicity（Dulaglutide，度拉糖肽，中文商品名：度易达）为GLP-1受体激动剂类生物药，其在全球2型糖尿病管理中占据重要地位。尽管目前GLP-1药物以多肽新药（如semaglutide和tirzepatide）为主导，但生物类似药仍可能凭借医保放量和价格优势切入市场，特别是在发展中国家。需要指出的是，虽然度拉糖肽的名称似乎显示其分子模态为多肽，但根据FDA的标准，该药物属于蛋白质（氨基酸残基数量远大于40）。Repatha（Evolocumab，依洛尤单抗，中文商品名：瑞百安）则是降脂治疗领域的明星产品，靶向PCSK9，技术结构相对清晰，安进的原研市场或将迎来仿制挑战者。另一方面，罕见病药物如Myalept（metreleptin，中文商品名：美曲普汀）与Sylvant（siltuximab，司妥昔单抗，中文商品名：萨温珂）分别用于脂肪营养不良与Castleman病，尽管患者基数较小，但在定价上长期维持高位，仿制药若成功推出，将显著影响药企盈利结构。2028年：免疫肿瘤黄金时代走向价格重估2028年将是免疫肿瘤药物市场重新洗牌的关键时刻。默沙东的Keytruda（Pembrolizumab，帕博利珠单抗，中文商品名：可瑞达）与BMS的Opdivo（Nivolumab，纳武利尤单抗，中文商品名：欧狄沃）这两大令人高山仰止的肿瘤学产品均将步入专利到期周期，这两款超巨重磅炸弹PD-1免疫检查点抑制剂几乎主导了全球多个癌种的一线免疫治疗格局。尽管其结构相对标准，技术仿制障碍较低，但监管机构对生物类似药在免疫肿瘤领域的临床一致性要求极高，加之其适应症广泛，将使得生物类似药的开发必须精细划分适应症并分阶段获批，逐步蚕食市场份额。专利到期将加速PD-1药物在中低收入市场的普及，也可能促使原研药大幅调整定价策略，以留存市场份额。2029年：自身免疫与血液瘤市场再迎竞逐到2029年，更多大体量产品将面对专利悬崖 。强生的Darzalex（Daratumumab，达雷妥尤单抗，中文商品名 ：兆珂）作为CD38靶点的多发性骨髓瘤生物制剂，在全球范围内维持了稳定的市场扩张，是多发性骨髓瘤治疗的主力产品，随着其全球销售额突破百亿美元，专利到期后的市场争夺战料将激烈。其复杂糖基化模式以及Fc改造机制为仿制企业带来技术挑战，但在高价格驱动下，已有多家企业提前展开布局。Ocrevus（ocrelizumab，奥瑞珠单抗）则是罗氏在多发性硬化治疗中的核心资产，兼具高效与安全性，其结构仿制可行，但治疗窗要求精细，后续药物可能更注重使用便捷性与长期随访数据。诺华的Cosentyx（Secukinumab，司库奇尤单抗，中文名称：可善挺）与安进的Enbrel（Etanercept，依那西普）则均为成熟的自身免疫治疗药物，市场格局已经相对开放，生物类似药的渗透速度预计将更快，并可能引导IL通路及TNF通路药物价格进一步下探。而Enbrel在美国延长专利的多年争议也提醒市场，专利并非铁板一块，法律诉讼、授权模式与市场准入政策同样决定产品生命周期的真正终点。结语：从专利到市场，生物制剂的新周期已然开启随着2025–2029年间一系列重磅生物制剂的专利相继到期，原研药企需要重新审视生命周期管理策略，从新适应症拓展、给药方式创新，到自有生物类似药的内部布局，争取在失去专利保护后依然保有市场份额。而对于仿制药企业而言，技术平台成熟度、质量一致性、监管路径优化以及成本控制将是能否在新一轮“生物仿制潮”中脱颖而出的关键。更值得注意的是，随着医保体系对高值药物价格的持续挤压，以及新兴市场国家生物药仿制能力的提升，这一轮专利悬崖或许将不仅仅是一个商业接力的过程，更可能成为全球药物可及性提升与创新转化效率再平衡的重要契机。附表 2025-2029年面临专利悬崖的部分生物制剂END2025金笔奖征文即将截止，速来投稿！领取CPHI & PMEC China 2025展会门票来源：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~

SAN DIEGO--( BUSINESS WIRE )-- Entos ® Pharmaceuticals (Entos) , a clinical-stage genetic medicines company committed to using its Fusogenix™ PLV™ technology to develop cures and improve the lives of patients and their families, announced today that the California Institute for Regenerative Medicine (CIRM) has awarded the company a $4M USD grant. The funds will support the completion of IND-enabling activities for the development of ENTLEP001, a durable genetic medicine for the treatment of congenital generalized lipodystrophy (CGL). CGL is a rare genetic disorder caused by mutations in the human leptin gene. People with CGL are leptin-deficient and cannot make adipose tissue. The disorder is associated with severe, hard-to-treat diabetes, hypertriglyceridemia, and potential complications affecting the liver and heart. ENTLEP001 is a systemically administered investigational gene therapy using the Fusogenix PLV platform to express unmodified human leptin in the body. The treatment is designed to be durable, redosable, and provide biologically relevant levels of native human leptin expression. Preclinical studies with ENTLEP001 using a leptin-deficient mouse model resulted in clinically relevant leptin expression, disease-modifying activity including normalization of glucose and insulin levels, and decreased weight gain and food intake. The Fusogenix PLV platform is a fusion-powered delivery system for genetic medicines that combines the best aspects of viral and non-viral approaches. Using a completely new mechanism for intracellular delivery of RNA, DNA and gene editing therapies, Fusogenix PLV is suitable for a wide range of best-in-class genetic medicines. Details regarding the platform’s safety, efficacy, and biodistribution in various animal models were published in Cell in September 2024. "Despite advancements in CGL treatment with FDA-approved metreleptin, there are still significant unmet needs," said Steve Chen, MD, CMO of Entos Pharmaceuticals. "Metreleptin requires daily subcutaneous injections and in some patients is associated with significant injection site adverse events. Although rare, there are reported cases of neutralizing anti-leptin antibody in patients receiving metreleptin. In contrast, ENTLEP001 is a genetic medicine that expresses native human leptin and may require dosing only once or twice a year, eliminating injection site reactions, simplifying patient compliance, and improving outcomes.” "This award from CIRM is an important validation for our lead program in CGL as we work to advance our second product into the clinic using the Fusogenix PLV platform,” said John Lewis, CEO of Entos Pharmaceuticals. “We deeply appreciate their support and recognition of the crucial need to address rare genetic disorders like congenital generalized lipodystrophy and the potential for novel genetic medicine approaches like the Fusogenix PLV to create life-changing treatments for patients and their families." About Congenital Generalized Lipodystrophy (CGL) Congenital generalized lipodystrophy (CGL), also known as Berardinelli-Seip syndrome, is a rare genetic disorder characterized by the near total loss of adipose tissue associated with extreme muscularity that is often present at birth or soon thereafter. CGL is associated with metabolic complications related to insulin resistance such as severe diabetes and hypertriglyceridemia. Diabetes associated with CGL is often very difficult to treat. Additional complications affecting the liver and heart can also occur. The symptoms and severity of CGL can vary greatly from one person to another. CGL is caused by mutations in the human leptin gene LEP . About Entos Pharmaceuticals Inc. A new reality in genetic medicine lies ahead, one that will be ushered in with the advent of safe, effective, and re-dosable nucleic acid delivery technologies. Since its inception in 2016, Entos® has been dedicated to advancing next-generation genetic medicines using our proprietary Fusogenix™ PLV™ drug delivery system. The Fusogenix PLV platform is formulated with FAST proteins to enable the delivery of nucleic acid to target cells through direct fusion. Entos is pioneering the development of life-changing medicines for patients and has partnered with global companies, such as Eli Lilly, to accelerate and expand the impact of our platform. Entos Pharmaceuticals Inc. is headquartered in Edmonton, Canada, with its wholly owned U.S. and U.K. subsidiaries based in San Diego, California and London, United Kingdom, respectively. For more information, visit www.entospharma.com , or follow Entos on LinkedIn . About California Institute for Regenerative Medicine (CIRM) At CIRM, we never forget that we were created by the people of California to accelerate stem cell treatments to patients with unmet medical needs, and act with a sense of urgency to succeed in that mission. To meet this challenge, our team of highly trained and experienced professionals actively partners with both academia and industry in a hands-on, entrepreneurial environment to fast track the development of today’s most promising stem cell technologies. With $5.5 billion in funding and more than 150 active stem cell programs in our portfolio, CIRM is the world’s largest institution dedicated to helping people by bringing the future of cellular medicine closer to reality. For more information go to www.cirm.ca.gov . Forward Looking Statements This press release contains forward-looking statements, within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements contained in this press release include statements regarding Entos and its belief as to the mode of action and potential and benefits of the Fusogenix proteolipid vehicle platform and other statements related to anticipated developments in the Company’s business and technologies. In any forward-looking statement in which Entos expresses an expectation or belief as to future results, such expectations or beliefs are expressed in good faith and are believed to have a reasonable basis, but there can be no assurance that the statement or expectation, or belief will be achieved. Such forward-looking statements involve known and unknown risks and uncertainties, which could cause the Company’s actual results to differ materially from those in the forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources to pursue research and development projects, the efficacy of Fusogenix as a nucleic acid delivery vehicle, uncertainties related to the research and development of pharmaceuticals, uncertainties related to the regulatory process and general changes to the economic environment. We may incur expenses or delays relating to such events outside of our control, which could have a material adverse impact on our business, operating results, and financial condition. Investors should consult with the U.S. Securities Commission for additional information on risks and uncertainties relating to the forward-looking statements. Investors are cautioned against placing undue reliance on forward-looking statements. The Company does not undertake any obligation to update these forward-looking statements except as required by applicable laws. Entos ® word mark and design logo, Fusogenix™ and PLV™ are registered trademarks of Entos Pharmaceuticals Inc. All other trademarks and registered trademarks are the property of their respective owners.