Lutetium (177 Lu) Vipivotide Tetraxetan

诺华正在下一盘大棋！ 近期，诺华大动作频频，不仅以潜在总额53.6亿美元与舶望制药合作开发多款心血管siRNA疗法，还接连加码神经科学领域，先是以超8亿美元与BioArctic合作开发神经退行性疾病新疗法，又斥资22亿美元引进Arrowhead一款治疗帕金森病的siRNA疗法。 剥离了仿制药业务后的诺华，开始全力出击siRNA疗法、聚焦创新药，带来了不少看点。 TONACEA 01 全力出击siRNA疗法 诺华之所以与舶望制药深化心血管领域合作，背后有着深层逻辑。 心血管-肾脏-代谢业务（CRM）是诺华四大核心治疗领域之一，2025年上半年实现收入同比增长26%至51.73亿美元，成为公司第二大收入来源。其中，重磅心衰药物Entresto（沙库巴曲缬沙坦）实现销售额同比增长22%至46.18亿美元，贡献了CRM业务90%的营收，而且占公司总收入的比重近17%%，是诺华第一大支柱产品。 不过，作为一款已上市11年的产品，Entresto面临增长乏力困境，加之专利即将到期、仿制药将进入美国市场，以及2026年开始执行医保价格（降幅53%），销售额将受到较大冲击。 基于此，诺华在今年3月宣布调整心血管业务的商业化战略，将重心转移至其他高潜力心血管药物，包括销售额保持高速增长的Leqvio（inclisiran，英克司兰钠），以及3款肾病新药：CFB抑制剂Fabhalta（伊普可泮）、ETA拮抗剂EXV811（阿曲生坦）和在研IgA肾病新药Zigakibart。 图片来源：华福证券研报 为了补充产品管线，诺华还两度携手RNAi赛道黑马舶望制药：先是就两款心血管siRNA药物达成潜在总额超41亿美元的合作，又在近期就四款siRNA管线达成总额超53亿美元的合作。 根据近期达成的合作协议，舶望制药将授予诺华两款处于发现阶段的下一代siRNA分子（针对重度高甘油三酯血症及混合性血脂异常）的中国境外许可权、一款正在中美两地开展II期临床的BW-00112（ANGPTL3 siRNA）的优先谈判权、一款预计2026年启动Ⅰ期研究的siRNA候选药物的中国境外许可权。 不得不说，诺华对siRNA疗法是真爱啊。 毕竟，长效PCSK9 siRNA降血脂新药Leqvio，自上市以来一直保持高速增长态势，让诺华尝到了甜头，2025年上半年，实现销售额同比增长66%至5.55亿美元，今年有望成为“十亿美元分子”。 Leqvio成功验证了siRNA在慢病领域的商业化潜力，并推动其他RNAi疗法探索高血压、糖尿病等。例如，罗氏和Alnylam在近期宣布，将启动一项III期心血管结局试验（CVOT），以评估RNAi疗法Zilebesiran降低未控制高血压患者发生重大心血管不良事件风险的能力。 值得注意的是，siRNA疗法还有望拓展至中枢神经系统（CNS）疾病领域。就在近期，诺华以潜在总额22亿美元从Arrowhead引进了一款治疗帕金森病的临床前阶段siRNA疗法。 此次合作，不仅彰显了诺华在siRNA药物领域的深度布局，更暗藏其抢占下一个“黄金赛道”的野心。 TONACEA 02 持续加码神经科学 除了CRM业务，神经科学也是诺华四大核心治疗领域之一：2025年上半年，实现收入同比增长23%至27.59亿美元，占公司总收入比例提升至10.11%。 诺华在神经科学领域的主要产品包括：CD20单抗Kesimpta（奥法妥木单抗）、一次性基因疗法Zolgensma（OAV101），2024年分别实现销售额32.24亿美元（+49% ）、12.14亿美元（+2%）。 Kesimpta适用于成人复发型多发性硬化（RMS）。多发性硬化（MS）是一种免疫介导的中枢神经系统炎性脱髓鞘疾病。凭借居家注射的便利性，Kesimpta保持强劲的增长势头，2025年上半年同比增长38%至19.76亿美元，验证了B细胞疗法的市场认可度。 Zolgensma是诺华87亿美元收购AveXis所获得的一种基于腺相关病毒（AAV）载体的基因治疗药物，也是基因疗法领域的首款“重磅炸弹”，用于治疗罕见病脊髓性肌萎缩症（SMA），每剂210万美元（约合人民币1500万元）。 不过，由于市场天花板可见、天价带来的市场准入与支付压力及市场竞争加剧等原因，这两年Zolgensma销售额持续下滑，2025年上半年实现收入同比下降3.11%至6.24亿美元。 可见，诺华的神经科学业务出现了与CRM业务类似的情况：亟待新品补位。 图片来源：方正证券研报 基于此，诺华开启了“买买买”模式：2024年，以11亿美元收购Kate Therapeutics，拓展神经基因治疗领域战略布局；2025年，以超8亿美元与BioArctic合作开发神经退行性疾病新疗法，以22亿美元引进Arrowhead的帕金森病siRNA疗法。 纵观其战略布局，诺华在神经科学领域的规划极具前瞻性，旨在抢占下一代治疗技术的制高点。 例如，诺华选择收购Kate Therapeutics，是为了显著增强其在基因疗法和神经科学创新领域的战略布局。 Kate专注于开发基于AAV的基因疗法，用于治疗遗传性神经肌肉疾病，包括杜氏肌营养不良症（DMD）、面肩肱型肌营养不良症（FSHD），其中最成熟的候选药物KT430，已授权安斯泰来合作开发，用于治疗X连锁肌管性肌病。 与诺华达成授权合作的BioArctic大有来头，后者专注于可以延缓或阻止神经退行性疾病进展的创新疗法。 世界上第一种被证明可以减缓疾病进展并减少早期阿尔茨海默病认知障碍的药物——仑卡奈单抗（lecanemab，Leqembi），正是由BioArctic发现了原型抗体mAb158（仑卡奈单抗的前身），并与负责后期开发、临床试验和商业化的卫材共同开发的。 更关键的是，我们还能从诺华引进帕金森siRNA疗法窥见其差异化战略。 TONACEA 03 将差异化进行到底 诺华的差异化战略，体现在不追热门的ADC、GLP-1赛道，而是“绕过红海、开辟蓝海”，深度布局核药、小核酸药物、细胞与基因疗法。 尤其在核药领域，诺华已经尝到了大甜头：Pluvicto已在2024年成为“重磅炸弹药物”；另一款核药Lutathera今年上半年实现销售额同比增长16%至4亿美元，也有望成为“十亿美元分子”。 为了加强在放射性配体疗法（RLT）领域的领导地位，诺华一直在“买买买”，去年还收购Mariana Oncology，拿下了针对小细胞肺癌（SCLC）的基于锕的先导RLT项目MC-339。 而在小核酸药物板块，诺华主要布局反义寡核苷酸（ASO）和小干扰RNA（siRNA），今年还斥资17亿美元收购肾脏疾病药物研发公司Regulus，获得已进入III期临床的miRNA药物Farabursen。 Farabursen是针对miR-17靶点的下一代寡核苷酸，用于治疗常染色体显性遗传性多囊肾病（ADPKD）这一严重的肾脏疾病。 诺华药品开发部总裁兼首席医学官Shreeram Aradhye表示，“目前ADPKD患者的治疗选择有限，Farabursen作为一种潜在的首创药物，有望在疗效、耐受性和安全性方面优于现有的标准治疗方案。ADPKD是全球范围内，引起肾衰竭最常见的遗传性原因。” 图片来源：方正证券研报 针对siRNA疗法，诺华还将触手伸至CNS领域。此前，艾伯维扬言“明年将成为业内最大的CNS公司”，诺华自然不甘落后。 在帕金森病治疗领域，艾伯维拥有Duodopa（左旋多巴/卡比多巴凝胶）和销售峰值有望超20亿美元的帕金森病复方疗法Vyalev，并收购Cerevel Therapeutics拿下了多巴胺D1/D5受体部分激动剂Tavapadon；反观诺华选择siRNA疗法突围路线，将差异化进行到底。 诺华斥资22亿美元引进的ARO-SNCA，便是一款临床前阶段的siRNA疗法，利用Arrowhead专有靶向RNAi分子（TRiM™）平台进行皮下给药和向中枢神经系统递送，旨在靶向编码α-突触核蛋白的基因，作为帕金森病和其他突触核蛋白病患者的潜在治疗方法。 诺华生物医学研究总裁FionaMar shall表示：“帕金森病等神经退行性疾病影响着全球数百万患者。我们认为ArrowheadTRiM™技术具有巨大潜力，可在关键的大脑结构中实现广泛有效的递送，这对于看到RNA药物在神经退行性病变中的全面益处是必要的。” 正如Leqvio开创了siRNA用于慢性病的新时代，诺华此举也是为了防止在下一代CNS疗法中掉队。若能成功，ARO-SNCA将重塑帕金森病治疗范式，并为诺华带来可观的收入。 此次合作，诺华还将在TRiM™平台开发的产品线之外选择其他合作靶点。可见，TRiM™平台是“会下金蛋的鸡”，诺华看中的是其持续制造“重磅炸弹药物”的潜力。 如此看来，诺华选择重金投入，既是进攻性的开疆拓土，也是防御性的战略卡位。 — 结语 — 在巨头林立的创新药竞赛中，诺华选择了一条差异化且极具前瞻性的突围路径。这一选择的核心驱动力源于对核心产品增长乏力的未雨绸缪。 为此，诺华启动了“买买买”模式、双线并行的“补位”战略。这种聚焦于小核酸、核药等前沿领域的选择，既规避了同质化竞争，又通过深耕技术驱动的创新路径，为其构建了独特的长期壁垒与护城河。 参考资料： 1.诺华的财报、公告、官微 2.《20250822-医药生物行业：诺华2025H1业绩超预期，小核酸药物Leqvio增速领跑》，方正证券研报 3.华福证券研报  喜欢我们文章的朋友点个“在看”和“赞”吧，不然微信推送规则改变，有可能每天都会错过我们哦~ 免责声明 “汇聚南药”公众号所转载文章来源于其他公众号平台，主要目的在于分享行业相关知识，传递当前最新资讯。图片、文章版权均属于原作者所有，如有侵权，请在留言栏及时告知，我们会在24小时内删除相关信息。 信息来源：同写意 往期推荐 本平台不对转载文章的观点负责，文章所包含内容的准确性、可靠性或完整性提供任何明示暗示的保证。

iStock, Oksana Sazhnieva With a flurry of recent Big Pharma investment in radiopharmaceutical therapeutics, the FDA issued draft guidance last month in a move former FDA Commissioner Stephen Hahn sees as the regulator “trying to get ahead on a new set of therapy that they see becoming very important for cancer.” After its March 2022 approval for certain types of castration-resistant prostate cancer, Novartis’ Pluvicto hit blockbuster status last year, clearing $1 billion in sales. Just over three years later, the radiopharmaceutical sector is pushing at the edges, with some projections putting the market at more than $16 billion by 2033 , and powerhouses like AstraZeneca, Bayer and, of course, Novartis are seeking a piece of the pie. Last month, the FDA provided these drugmakers with new draft guidance , a move former FDA Commissioner Stephen Hahn welcomed. “I think what we’re seeing here is the agency trying to get ahead on a new set of therapies that they see becoming very important for cancer,” Hahn, who recently accepted the CEO position at North Carolina–based CDMO Nucleus RadioPharma, told BioSpace in an interview. “It’s nice to see the agency provide some clarity on what expectations should be.” Hahn observed the accelerated trend in new drug applications (NDAs) and investigational new drug (IND) applications for radiopharmaceuticals. When this happens, he said, “it becomes pretty clear to review teams and leadership that there needs to be some consistency in the development process and what’s needed for approval.” In April 2024, Novartis picked up another radiopharmaceutical approval , this time for Lutathera for pediatric patients with gastroenteropancreatic neuroendocrine tumors. Together with Pluvicto, sales totaled more than $2 billion that year. But Novartis could soon face competition, as a spate of large and small companies including specialty outfits like Perspective Therapeutics and giants like Eli Lilly, AstraZeneca and Bristol Myers Squibb also working in the space. Hahn sees the FDA’s actions as providing a greenlight for the industry, with the regulator signaling that it expects to see the flow of radiopharma applications increasing further.With all the considerations that new modalities engender, he said the regulator is trying to keep tabs on issues that might occur down-the-line—an arduous process with which Hahn has first-hand experience. Andrew Tsai, biopharma analyst and senior vice president at Jefferies, agreed that the FDA was driven to issue the guidance based on the increasing number of players in the space. “It’s good to know that the FDA is paying attention, and it suggests that the FDA wants to collaborate by issuing the guidance,” he told BioSpace . “They didn’t have to do this.” A Whole New Field The draft guidance, which is open for comments until Oct. 20, focuses on a range of subjects, particularly dose optimization, clinical trial design and patient selection, as well as safety concerns. Radioligand therapies (RLT) comprise a radioactive isotope conjugated to a targeting molecule that guides the isotope to a specific tissue. In Pluvicto’s case, a lutetium isotope is joined with a prostate-targeting molecule. But the dosing for these types of therapies has often been based on traditional radiation treatments that has been used to treat cancer for more than a century.   Mike Ritchie, chief commercial officer at cancer-focused CRO Champions Oncology, described radiation as “quite literally an external machine that shoots a beam into sites of tumors.” “All of the clinical safeguards were around that type of radiation therapy,” he told BioSpace . “Fast forward to now, there’s a new field where we’re injecting radiation into patients, with a targeting moiety that treats the tumor in a targeted way.” Since targeted radiotherapy is still a new field, the FDA is seeking more details in applications—such as number of doses tested and toxicities that occur—because there is simply less familiarity with the modality at both the agency and across the sector. “They’re saying that ‘we don’t know what we don’t know,’” Ritchie said. Depending on the type of radiotherapy, the FDA may even ask sponsors to show a reading of the level of radiation within each organ, he continued. According to the new guidance, sponsors applying for INDs and NDAs should consider new safety precautions and exposure standards, given that RLTs get isotopes to tissues in a far more precise way than an external beam. For instance, becauseif the antigen is specific enough, RLTs should in theory only accumulate in the target organ. However, because many cancers express genes in off-target tissues, sponsors will need to keep tabs on radiation levels in multiple tissues during clinical trials. Ritchie compared RLTs to a therapy with a similar structure: antibody-drug conjugates. The first ever FDA-approved ADC, Pfizer’s Mylotarg, got the greenlight in 2000 but was later withdrawn from the market later due to safety issues. That’s something the FDA would want to avoid with another new modality, he said.  In the past, “ADCs have been clean in monkeys and in humans there was toxicity,” Ritchie continued. “The FDA is just doing what it should be: keeping patients first.” A Healthy Sign The FDA’s move to issue guidance on radiopharmaceuticals is a healthy sign for a sector that has seen a flurry of activity over the last few years. In 2024, four different Big Pharmas—Novartis, Eli Lilly, AstraZeneca and Bristol Myers Squibb—all made low single-digit billion dollar acquisitions of small radiopharmaceutical companies. “There’s a good amount of money flowing in a space that people didn’t really think about 5, 10 years ago,” Tsai said. “At least in the investor’s lens, it’s caught people’s attention.” To Hahn, the field is already on track to improve patients’ lives. He noted that Pluvicto’s initial approval was limited to subsets of prostate cancer patients, but the therapy has picked up multiple label expansions just this year. “We really didn’t have an alternative to hormones and then chemotherapy in [castration-resistant prostate cancer] and chemotherapy has relatively modest effectiveness in that disease.” There was significant unmet medical need in castration or hormone-resistant prostate cancer, Hahn said, “and being able to apply [radiopharmaceuticals], extend survival, improve quality of life and not make people sick with it is a really important advance.” Hahn said he envisions a world where radiopharmaceuticals can be combined with currently available immuno-oncology agents to double up on both modalities’ effectiveness. “One could imagine that being the pathway of development in diseases that are very difficult to treat,” he said, like breast cancer, lung cancer and malignant melanomas. “There’s a lot of situations where we really don’t have good tools or the tools are pretty toxic,” Hahn told BioSpace . “As you know in oncology . . . there are a lot of unmet medical needs.”