Lutetium (177 Lu) Vipivotide Tetraxetan

iStock, cagkansayin To successfully challenge Novartis on two planned fronts, Curium will need to overcome the unique challenges posed by radiopharmaceutical supply to get products to patients and win market share. Novartis’ blockbuster radioligand therapy business faces emerging threats. Curium received FDA approval for Bexlutry, its rival to Novartis’ Lutathera, in September, and the biotech is in talks with the agency about a filing for a separate radiopharma treatment that could challenge the Swiss drugmaker’s Pluvicto. Meanwhile, after agreeing to a $1.65 billion buyout of ITM Isotope Technologies Munich, Telix Pharmaceuticals will soon own therapies that could compete with both Novartis products. The stakes are high. Lutathera and Pluvicto generated $1.7 billion over the first half of the year. Sales of the products are increasing at a time when Novartis’ growth prospects face scrutiny. Competition could increase pressure on Novartis, but the unique, exacting requirements of radioligand therapy (RLT) supply mean FDA approval is only one step toward a viable challenge for treatments currently on the market. To compete, Curium and other potential challengers will need to master three steps. 1. Create a resilient manufacturing footprint Access to lutetium-177 (Lu-177), the radioactive isotope in Lutathera, Pluvicto and Curium’s challengers, is the foundation of RLT supply. While the University of Missouri Research Reactor provides Lu-177 to Novartis, Curium has established multiple lines to produce its own Lu-177, North America CEO Michael Patterson told BioSpace in August, making it currently the only vertically integrated RLT manufacturer. Curium secured access to Lu-177 capacity in 2024 by partnering with NRG PALLAS in the Netherlands and the Institut Laue–Langevin in France. That year, the company also opened a Lu-177 production facility in the Netherlands to support plans to supply the radioisotope to 100,000 patients globally in five years. The actions reflect a broader focus on making the supply chain resilient. Controlling isotope production will enable Curium to adapt to demand, Patterson said, and installing multiple manufacturing lines at an Indiana facility will provide backup options. Initially, Novartis only made Pluvicto in Italy. Lacking supply chain redundancy, the company struggled to get Pluvicto to patients when it suffered manufacturing interruptions, and the RLT ended up on the FDA’s shortage list for part of 2023. Novartis boosted its Pluvicto output and supply resilience by starting production in New Jersey in 2023 and in Indiana in 2024. Manufacturing Western licensing deals for Chinese radioligand therapies to jump in 2027, Sleuth forecasts Deals for Chinese radiopharmaceutical assets have been rare to date and there is a limited pool of potential Western buyers available, Sleuth said. September 21, 2026 · 2 min read · Nick Paul Taylor Read more 2. Reliably get RLTs from plants to patients Patterson, like others in the industry, uses the ice cube analogy to explain the challenge of getting RLTs to patients. Much as an ice cube melts, radioisotopes immediately start to decay, creating a deadline for getting drugs to patients. Lu-177 has a half-life of 6.7 days. The tight turnaround times mean delays that would be inconvenient when shipping other modalities can render RLTs unusable. Created when IBA Molecular and Mallinckrodt Nuclear Medicine merged in 2017, Curium is familiar with these logistical challenges. Curium uses “a combination of truck routes and commercial airlines, weaving in charter aircraft, to make sure that we get product to the physicians on time,” Patterson said. Being based in the Midwest, Curium can reach many U.S. locations by truck and, because they offer more control and reliability, the company favors ground routes where possible, Patterson said. Patterson’s preference for trucks is shared by other radiopharma leaders. However, the mix of a decaying product, treatment centers outside the U.S. mainland and hard-to-predict factors such as weather mean a flexible mix of transport is needed. Curium uses couriers for the last legs of journeys and charters planes when needed, such as during heavy snowstorms last winter, Patterson said. 3. Secure space at treatment centers Curium could master every step from isotope production to last-mile logistics and still struggle to grow sales of its RLTs. That scenario aligns with the assessment of the current constraints on RLT availability that Sleuth, a biopharma intelligence platform, provided in its third-quarter radiopharma report, which points the finger squarely at “delivery infrastructure.” “Watch how the availability of nuclear-medicine chairs, limited radiopharmacy staffing and difficulties in drug reimbursement dampen the growth rate, as no molecule can fix a shortage of treatment slots,” Sleuth said, discussing RLTs in general, not Curium’s assets in particular. Manufacturing Preparing for Novartis showdown, Curium touts value of radiopharma supply resiliency While Novartis’ Pluvicto is a blockbuster, Curium heads into talks with the FDA about the review of its rival drug candidate believing a competing product can make the supply chain more resilient. August 25, 2026 · 4 min read · Nick Paul Taylor Read more Sleuth argued that the sector shifted in 2024, following Novartis’ success at increasing Pluvicto production, from being constrained by manufacturing supply to being limited by treatment capacity. Despite improvements in the supply chain, patients can still face a two- to six-week wait to receive an RLT, Sleuth said. The waits persist despite healthcare providers’ efforts to increase treatment capacity. Novartis currently lists more than 700 Pluvicto treatment centers, compared to 86 in November 2022. Yet Sleuth still sees treatment capacity as a “near-term ceiling” on RLT growth. Adding capacity to administer RLTs poses challenges not seen when working with other modalities. Sites must have infrastructure and processes that support radiation protection and shielding, establish teams with multiple specialties and receive a license. If Curium wins FDA approval, it will be able to draw on long-standing connections to nuclear medicine physicians as it works to win market share. “Certainly, we think that there are benefits to being in nuclear medicine for decades,” Patterson said. Subscribe to Manufacturing Brief! Get a weekly update including our take on the most critical issues impacting manufacturing. June 12, 2025 Read more

全球还没有一款获批：国内首款前列腺癌 PSMA/STEAP1 双抗 ADC 获批临床，家属该怎么看这条消息？ 9 月 9 日，诺诚健华宣布，自主研发的 ICP-B381 获国家药监局药品审评中心（CDE）批准开展临床试验，用于治疗前列腺癌等实体瘤。它同时瞄准两个靶点： PSMA 和 STEAP1 ，是公司第一款双抗 ADC，全球目前也没有同类药物获批上市。 先说结论： 这是 临床试验批件 ，不是疗效数据，目前只有动物实验结果； 它想解决的问题是真实存在的：单靶点药物容易因为肿瘤靶点表达不均一而"漏网"； 但把 PSMA 和 STEAP1 结合做成药物，全球已经有不少前车之鉴，有的因为副作用太大而放弃，有的疗效不够； 目前唯一在人体里跑通、显示出明确疗效的同类思路，是一款 双抗 （不是 ADC）——但它的细胞因子释放综合征发生率很高。 一、PSMA 和 STEAP1 是什么，为什么要"双靶点" PSMA（前列腺特异性膜抗原）和 STEAP1，都是在前列腺癌细胞表面大量出现、正常组织里很少见的蛋白，是这些年药物设计最爱瞄准的两个靶点。 单靶点药物的软肋在于"漏网之鱼"。 同一个病人体内，不同的肿瘤病灶，甚至同一病灶里的不同细胞，PSMA 的表达量可能差别很大；有些患者治疗一段时间后，PSMA 表达还会下降，导致药物"抓不住"肿瘤了。 ICP-B381 的思路是：只要肿瘤细胞表达 PSMA 或 STEAP1 中任意一个，药物就能识别并杀伤它，理论上能扩大覆盖面、降低"因为靶点丢失而耐药"的风险。 这不是全新的想法，全球在 PSMA 和 STEAP1 这两个靶点上，已经各自走过不少弯路，也各自有过突破，值得放在一起看。 二、ICP-B381 目前到了哪一步 药物类型 ：双抗 ADC（抗体偶联药物），由人源化抗 PSMA/STEAP1 抗体，加上公司自研的不可逆连接子和细胞毒性载荷偶联而成，同一套连接子-载荷技术平台也用在公司另外两款单靶点 ADC 上。 目前的证据只有动物实验 ：在 22Rv1 人前列腺癌异种移植模型中，显示出强效、剂量依赖性的抗肿瘤活性；同等剂量下，效果优于对应的单靶点 PSMA-ADC 和 STEAP1-ADC，且耐受性良好。 这次获批的，是开展临床试验的许可 ，也就是可以开始在人体里做安全性和初步疗效的探索，通常从 I 期开始。目前没有任何人体数据。 公司称，全球尚无靶向 PSMA 和 STEAP1 的双抗 ADC 获批上市。 动物实验有效，不代表在人身上一定有效，也不代表安全。 这是新药研发里最容易被忽略的一句话——从临床前到 I 期，再到证明疗效，通常要走好几年，多数在研药物会在这个过程中被淘汰。 三、STEAP1：已经有药物在人体里跑出了数据，但副作用不小 STEAP1 这个靶点上，进展最快的是安进公司的 xaluritamig（AMG 509） ，它不是 ADC，而是一种"双特异性 T 细胞衔接抗体"：一头抓住肿瘤细胞上的 STEAP1，一头抓住免疫系统的 T 细胞，把 T 细胞拉过去杀伤肿瘤。这类药物和你可能听过的 PD-1/PD-L1 抑制剂完全不同，作用机制更直接、也更"暴力"。 在重度经治的转移性去势抵抗性前列腺癌患者中： 整体人群 PSA50 缓解率 （PSA 下降超过 50%）约 49%， PSA90 约 27%–28%； 在较高剂量组，PSA50 可达约 59%，影像学客观缓解率（ORR）约 41%； 缓解持续时间中位数约 9.2 个月（数据仍不成熟）； 但 细胞因子释放综合征（CRS）非常常见 ，剂量爬坡阶段发生率约 97%，扩展阶段约 98%，其中 3 级及以上分别约 23% 和 16%。 这说明 STEAP1 是一个"打得中"的靶点，但代价是相当高比例的细胞因子释放综合征，这是 T 细胞被大量激活后的一种全身炎症反应，需要住院严密监测和及时处理。目前它还在 I 期，正在探索与内分泌治疗联合，以及与镥[177Lu]-PSMA 放射性核素治疗序贯使用的方案。 四、PSMA：这条路上，倒下的药物比成功的多 针对 PSMA 靶点，此前有好几款"双抗 T 细胞衔接剂"先后进入临床，结果大多不理想： 药物 结果 pasotuxizumab（AMG 212） 超 87% 患者出现治疗相关毒性，安进终止研发，转而开发下一代分子 acapatamab（AMG 160） 细胞因子释放综合征发生率约 84%，同时出现明显的抗药抗体问题，2025 年终止研发 JNJ-081 细胞因子释放综合征、抗药抗体问题突出，PSA50 缓解率仅约 8%，试验提前终止 JNJ-80038114 没有观察到影像学缓解，出现神经毒性和高比例的细胞因子释放综合征，提前终止 HPN424（三特异性） 疗效有限、毒性相对明显，PSA50 缓解率约 5% 也就是说， "瞄准 PSMA、拉 T 细胞来打"这条路，此前的几代药物大多倒在了副作用和疗效不够之间 。研发人员现在的思路是调低 T 细胞结合臂的"亲和力"，减少细胞因子释放综合征，比如 TNB-585，但这些都还处在很早期的阶段。 目前唯一获批用于晚期前列腺癌、并且明确靶向 PSMA 的药物，是 镥[177Lu]-PSMA-617 放射性核素治疗 （商品名 Pluvicto），已在美国和欧洲获批，但它是放射性配体疗法，不是抗体或 ADC，机制完全不同。 五、把 ICP-B381 放进这张图里看 这样看，ICP-B381 有两点特别之处： 它是 ADC ，不是 T 细胞衔接抗体。ADC 靠药物本身的化学毒性杀伤肿瘤细胞，不依赖大规模激活 T 细胞，理论上可能避开细胞因子释放综合征这类免疫相关的严重副作用——但这只是理论上的推测，实际安全性如何，要等人体数据。 它是 双靶点 ，而不是单靶点 PSMA 或单靶点 STEAP1。国际上多数在研药物还是单靶点，这条路目前在人体里的成功先例还很少。 换句话说，ICP-B381 想同时避开两类风险：ADC 机制上可能比 T 细胞衔接抗体更温和，双靶点设计想解决单靶点常见的"耐药逃逸"问题。这个设想是合理的，但 目前只是设想，没有一个字的人体证据支持 。 六、家属该怎么看这条新闻 这不是"新药上市"，离能用还很远。 I 期临床通常要先在几十位患者身上摸索安全剂量，之后才谈得上疗效，整个过程往往需要好几年。 "全球首款""国内首创"说明的是技术新颖，不代表已被证明有效或安全。 前面表格里那几款终止的药物，当年也都是"首创"的希望。 如果考虑参加临床试验 ，可以让主治医生帮忙判断入组条件、检测要求（比如是否需要确认肿瘤 PSMA 或 STEAP1 表达）和潜在风险，不要自行联系不明渠道。 现有治疗不变 ：目前晚期前列腺癌的标准武器仍是内分泌治疗、化疗、已获批的 PARP 抑制剂、镥[177Lu]-PSMA 放射性核素治疗等，是否调整方案，请与主治医生商量。 最后 双靶点 ADC 是一个合理的设计思路，也确实是国内药企在这个领域少见的布局。但从这两个靶点过去几年的人体试验历史看， "设计合理"和"人体安全有效"之间，还有很长的路要走 。这类消息值得关注，但现在还不是能影响治疗决策的阶段。 说明 ：本文基于诺诚健华官方公告及多家媒体报道（2026 年 9 月）、xaluritamig（AMG 509）在 ESMO 2023/2024 公布的 I 期数据、多篇关于 PSMA 靶向双特异性抗体的综述文献整理。ICP-B381 目前仅有临床前（动物实验）数据，尚无人体数据。本文不构成诊疗建议，请以主治医生意见为准。 #前列腺癌 #前列腺肿瘤 #前列腺癌症 #前列腺癌晚期治疗 #癌症 #癌症确诊日记