A Phase III, Multicenter, Randomized, Placebo Controlled, Double-blind Study to Assess Efficacy and Safety of Crizanlizumab (5 mg/kg) Versus Placebo, With or Without Hydroxyurea/Hydroxycarbamide Therapy, in Adolescent and Adult Sickle Cell Disease Patients With Frequent Vaso-Occlusive Crises

A phase III, multi-center, randomized, placebo-controlled, double-blind study to assess efficacy and safety of crizanlizumab (5 mg/kg) versus placebo, with or without hydroxyurea/hydroxycarbamide therapy, in adolescent and adult Sickle Cell Disease patients with frequent vaso-occlusive crises.

开始日期2024-10-24

申办/合作机构

Novartis Pharmaceuticals Canada, Inc.

NCT05469828

/ Not yet recruiting临床1/2期IIT

Crizanlizumab Improves Tissue Oxygen Supply Demand Matching in Patients With Sickle Cell Anemia

Hypothesis
Efficient unloading of oxygen to regions of high metabolic demand requires a healthy microvasculature to sense local oxygen tension and regulate flow, accordingly. In sickle cell disease patients, the investigators have demonstrated oxygen supply-demand mismatch, or SDM, in proportion to anemia severity. SDM occurs in both the peripheral circulation and the brain, and four characteristics: 1) Hyperemia beyond expected for the level of anemia, 2) Corresponding loss of vascular dilatory reserve, 3) Impaired oxygen unloading to the tissues, and 4) Tissue hypoxia. In sickle cell disease, red blood cell (RBC) and white blood cell (WBC) adhere to vascular endothelium triggering transient or irreversible microvascular damage as well as releasing vasoactive substances that contribute to microvascular dysregulation. The investigators postulate that ongoing microvascular damage/dysregulation in the setting of increased total blood flow contributes to SDM. The investigators believe SEG101, by lowering RBC and WBC adhesion to the microvasculature, will improve SDM and tissue oxygenation.
Objectives
Primary - The investigators will test whether SEG101 improves SDM in patients with sickle cell anemia by measuring the change in tissue oxygenation measured by near infrared spectroscopy (NIRS).
Secondary/Exploratory - The investigators will identify end-organ disease and whether improvement of SDM by SEG101 occurs in patients with sickle cell anemia.

开始日期2024-07-01

申办/合作机构

Children's Hospital Los Angeles

[+1]

NCT05909618

/ Recruiting临床2期IIT

An Open Label Phase 2 Study of Intravenously Administered Crizanlizumab Alone or in Combination With Nivolumab for Glioblastoma and Melanoma With Brain Metastases

A single-center, open-label, non-randomized phase I/II study to evaluate the efficacy, safety and tolerance of crizanlizumab monotherapy and in combination with nivolumab in patients with advanced glioblastoma (GB) who exhausted standard of care (SOC) therapy, patients with metastatic brain melanoma (MBM) and patients with newly diagnosed unmethylated GB.
Subjects will be screened for up to 28 days prior to treatment initiation. Eligible subjects will be allocated to one of 3 cohorts:
Cohort 1: Patients with metastatic melanoma with primarily diagnosed or newly progressing brain metastases who failed immunotherapy.
Cohort 2: Patients with recurrent or progressing GB following primary radiation therapy and temozolomide. Patients may have failed up to 2 prior systemic treatment lines (including temozolomide as adjuvant therapy) and are candidates for further treatment.
Cohort 3: Patients with newly diagnosed GB who were evaluated for methylguanine-DNA methyltransferase(MGMT) methylation status and have un-methylated MGMT promotor-therefore, they are not candidates for maintenance temozolomide therapy.

开始日期2023-07-11

申办/合作机构

Sheba Medical Center

100 项与 Crizanlizumab-TMCA 相关的临床结果

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100 项与 Crizanlizumab-TMCA 相关的转化医学

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100 项与 Crizanlizumab-TMCA 相关的专利（医药）

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项与 Crizanlizumab-TMCA 相关的文献（医药）

2026-07-01·Cancer research communications

Tumor-Associated Platelets Suppress T-cell Function and Promote Immune Evasion in TNBC via the P-selectin/P-selectin Glycoprotein Ligand 1 Pathway

Article

作者: Kane, Natalie ; Gautam, Deepa ; Davenport, Patricia ; Goggi, Giovanni ; Battinelli, Elisabeth M. ; Sullivan, Megan E. ; Baginska, Joanna ; Garrido-Castro, Ana C. ; Petrarca, Grace C. ; Brown, Jared ; McAllister, Sandra S. ; Roweth, Harvey G. ; Spasic, Milos ; Clarke, Emily M. ; Smith-Oliver, Margaret R.

Abstract:

Tumor-associated platelets (TAP), which are reprogrammed by tumor-derived signals to acquire immunosuppressive properties, represent an emerging mechanism of immune evasion in triple-negative breast cancer (TNBC). Although immune checkpoint inhibitors have shown promise, their efficacy is frequently limited by T-cell exhaustion and therapeutic resistance. In this study, we demonstrate that TAPs, unlike healthy circulating platelets, induce T-cell dysfunction through platelet-derived P-selectin, which engages P-selectin glycoprotein ligand 1 (PSGL-1) on T cells. This interaction promotes immunosuppressive signaling, driving T-cell exhaustion and impairing antitumor cytotoxicity. Using in vitro coculture systems and in vivo TNBC models, we show that disruption of the P-selectin–PSGL-1 axis, including pharmacologic blockade with the FDA-approved anti–P-selectin antibody crizanlizumab, restores T-cell function and enhances responsiveness to immune checkpoint blockade. Notably, PSGL-1, traditionally recognized for its role in leukocyte trafficking and immune regulation, is co-opted by TAPs to suppress T-cell activity, revealing a mechanism of platelet-mediated immune modulation. These findings establish TAPs as active regulators of antitumor immunity and identify the P-selectin–PSGL-1 axis as a therapeutically actionable target to overcome resistance to immunotherapy in TNBC.

Significance::

Tumor-associated platelets help TNBCs evade immune attack by suppressing T-cell function through P-selectin signaling. Blocking this pathway with crizanlizumab restores antitumor immunity and enhances response to immunotherapy, identifying a promising new combination treatment strategy for patients with this aggressive form of breast cancer.

2026-04-01·AMERICAN JOURNAL OF HEMATOLOGY

Advancing Sickle Cell Disease Treatment in Sub‐Saharan Africa: Challenges and Opportunities for Disease Modifying Therapies

Review

作者: Ambrose, Emmanuela E. ; Power‐Hays, Alexandra ; Dei‐Adomakoh, Yvonne

ABSTRACT:

Sickle cell disease (SCD) is a major individual and public health challenge in sub‐Saharan Africa, where over 5 million affected individuals live and where access to disease‐modifying treatment is limited. Despite established safety and efficacy of hydroxyurea, its use is limited across the region due to inconsistent healthcare infrastructure, high medication and laboratory costs, inadequate clinician training, and persistent disease stigma. Practical hydroxyurea dosing strategies, integration into national health plans, and a stronger supply chain are necessary to improve access to this life‐saving medication. Newly approved medications, such as L‐glutamine and crizanlizumab, may provide additional benefits to select patients, but are expensive and unavailable. The increased mortality observed in people on voxelotor in Africa highlights the need to ensure the safety of any new medication in varied settings through high‐quality research conducted on the continent. Overall, holistic strategies are needed to improve SCD care in Africa, such as universal screening with connection to comprehensive care that includes disease‐modifying treatment, community and healthcare worker education, centers of excellence, and capacity building. SCD management in Africa can be transformed by addressing systemic barriers and leveraging collaborative partnerships, leading to reduced mortality and alleviation of the individual and economic burdens of the disease. It is a moral and economic imperative to prioritize access to SCD treatment in Africa, the region with the greatest disease burden globally.

2026-02-10·Blood Advances

Low bone mineral density and pain impact in adults with sickle cell disease

Article

作者: Wun, Ted ; Wu, Qian V. ; Adesina, Oyebimpe O. ; Zemel, Babette ; Nalbant, Hande ; Nardo, Lorenzo ; Voutsinas, Jenna ; Rokni, Mehrad ; Teos, Leyla Y.

Abstract:

Low bone mineral density (BMD) is a prevalent skeletal finding in sickle cell disease (SCD), but its clinical consequences are poorly understood. We hypothesized that low BMD, independent of osteonecrosis (ON), would associate with pain in adults with SCD. In the SCD Bone Pain study, 53 ambulatory adults (64% females; mean age, 38 ± 11 years; 66% hemoglobin [Hb] SS/Sβ0 thalassemia) underwent dual-energy X-ray absorptiometry scans of their lumbar spine, hip, forearm, and whole body. They also completed the Adult Sickle Cell Quality of Life Measurement Information System pain impact questionnaire. Twenty-three participants (43%) had low BMD, defined as lumbar spine, total hip, or femoral neck BMD z scores of −2 or less. In multivariate linear regression, lumbar spine BMD z scores significantly changed by +0.31, −0.29, −0.14, and −1.3 for every unit increase in Hb, indirect bilirubin, and white blood cell count, and with crizanlizumab use, respectively. Pain impact T-scores significantly decreased (worsened) by 6.0 and 6.5 with reduced estimated glomerular filtration rate and chronic opioid therapy but increased (improved) by 3.8 for every unit increase in serum phosphate. The median [interquartile range] pain impact T-scores were significantly lower in participants with low BMD and ON (38.3 [37.4, 40.1]) than those with either low BMD (49.5 [43.6, 54.4]; P = 3 × 10−5) or ON (52.7 [45.3, 57]; P = 2 × 10−4) alone. Whether sickle cell–related low BMD results from impaired bone formation and/or accelerated bone loss remains unclear. Understanding how low bone density, with or without ON, mediates SCD pain warrants further investigation. This trial was registered at www.clinicaltrials.gov as #NCT05283148.

项与 Crizanlizumab-TMCA 相关的新闻（医药）

2026-07-31

·BioPharmaDive

Agios scraps sickle cell drug

Dive Brief:Agios Pharmaceuticals has decided not to further develop one of its more closely watched medicines as a treatment for sickle cell disease due to disappointing results from a mid-stage clinical trial.The drug, called tebapivat, did not demonstrate the level of differentiation required to support continued development, Agios said in a statement. Tebapivat has been billed as a next-generation version of another Agios medicine, mitapivat, which is already approved for use in two blood disorders. These drugs work by activating the pyruvate kinase enzyme thats essential for the health and survival of red blood cells.Shares of Agios were down 6.5%, to about $37.50 apiece, in mid-morning trading Tuesday. Leerink Partners analyst Andrew Berens wrote in a note to clients that, while his team had not yet attributed any of Agios stock value to tebapivat, the drug did represent the companys primary opportunity to differentiate itself in sickle cell disease from Novo Nordisk, which has its own once-daily enzyme activator that recently scored positive Phase 3 results.Dive Insight:Tebapivat is the latest example that drug companies, whether in research or in selling a product, find sickle cell significantly challenging.Just last month, Fulcrum Therapeutics, a Boston-area biotechnology firm, said it made the very difficult decision to stop advancing a potential sickle cell medicine because the Food and Drug Administration had unshakable concerns about safety risks. That medicine, pociredir, had already gone through early-stage human testing. But with no viable regulatory path forward for Fulcrums main asset, the company is now looking into strategic alternatives, including a possible sale.The Fulcrum update came less than a year after Pfizer unveiled underwhelming resultsfor a sickle cell drug it had picked up through the $5.4 billion acquisition Global Blood Therapeutics. In 2024, the pharmaceutical giant pulled a central asset in that deal, Oxbryta, from the market because of safety concerns. Novartis, too, withdrew a sickle cell therapy named Adakveo from the European market after regulators formally revoked the drugs authorization.Elsewhere, Sangamo Therapeutics and Graphite Bio each discontinued development of an experimental genetic medicine in 2023.Agios had another recent setback, disclosing in November mixed results from a late-stage trial evaluating mitapivat against sickle cell. The company is still forging ahead on that front, though, and expects an FDA approval decision by Nov. 1.In his client note, Berens wrote that tebapivats end places greater importance on the commercial execution of mitapivat and a smooth FDA review of the drugs expansion into sickle cell. It also puts more pressure on the company to succeed with its earlier-stage research projects and to take advantage of potential business development opportunities, the analyst added. '

临床3期并购上市批准临床结果细胞疗法

2026-07-02

·BioSpace

Vertex Announces US FDA Approval for Expanded Use of CASGEVY® for the Treatment of People Ages 2 Years and Older With Sickle Cell Disease or Transfusion-Dependent Beta Thalassemia

- First and only approved genetic therapy to treat children as young as 2 years for both severe sickle cell disease and transfusion-dependent beta thalassemia - - Approximately 5,500 additional children in the U.S. are now eligible for this established one-time therapy, expanding upon the prior FDA approval in people 12 years and older - - Regulatory review for label expansion underway in the Kingdom of Saudi Arabia and United Kingdom - BOSTON--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced today that the U.S. Food and Drug Administration (FDA) has approved expanded use of CASGEVY ® (exagamglogene autotemcel) for the treatment of people ages 2 years and older with either sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) or transfusion-dependent beta thalassemia (TDT). CASGEVY is the first approved genetic therapy indicated for children as young as 2 years for both SCD and TDT. “Just as we redefined what is possible in cystic fibrosis, our ambition is to transform the future for people living with sickle cell disease and transfusion-dependent beta thalassemia. The remarkable consistency of results across age groups reinforces the potential of CASGEVY to deliver durable, transformative benefits to those who have historically had limited options,” said Reshma Kewalramani, M.D., Chief Executive Officer and President, Vertex. “We’re deeply grateful to the patients, families and investigators who participated in the clinical trials that led to this historic approval, and we are ready to bring CASGEVY to children and their families across the U.S.” “Today’s approval offers renewed hope for children living with sickle cell disease or transfusion‑dependent beta thalassemia,” said Haydar Frangoul, M.D., M.S., Medical Director of HCA Healthcare’s Sarah Cannon Transplant and Cellular Therapy Program at TriStar Centennial Children’s Hospital, investigator with Sarah Cannon Research Institute (SCRI) and Member of Vertex’s SCD Program Steering Committee. “Earlier access to the transformative potential of this therapy will allow clinicians and families to consider treatment before years of cumulative damage from these life-shortening diseases take hold.” Vertex has established a network of independently operated, authorized treatment centers (ATCs) throughout the U.S. to offer CASGEVY to eligible patients through existing access and reimbursement pathways. Today, there are more than 75 activated ATCs in the U.S. The full list can be accessed at CASGEVY.com . About Sickle Cell Disease (SCD) Sickle cell disease (SCD) is a rare serious, inherited blood disease that is progressive and life‑shortening. The disease causes red blood cells to become rigid and misshapen, restricting blood flow and oxygen delivery to vital organs. Recurrent vaso‑occlusive crises (VOCs), unpredictable episodes of severe pain caused by blocked blood vessels, are a defining feature of SCD and frequently require hospitalization. Many patients experience these complications early in life, and over time, repeated VOCs and chronic anemia lead to progressive and irreversible organ damage, including damage to the brain, lungs, kidneys and heart. SCD places a substantial burden on patients and their families, who must manage frequent medical visits, hospitalizations, school and work disruptions, and the emotional toll of chronic pain and life‑threatening complications. Despite lifelong treatment, people with SCD and recurrent VOCs in the U.S. face shortened life expectancy, with a median age of death of approximately 45 years, report quality‑of‑life scores far below the general population and the estimated lifetime healthcare costs of managing the disease are $4–6 million. About Transfusion‑Dependent Beta Thalassemia (TDT) Transfusion‑dependent beta thalassemia (TDT) is a rare serious, inherited blood disease that is progressive and life‑shortening. The disease impairs the body’s ability to produce sufficient hemoglobin, limiting oxygen delivery to tissues and organs. People with TDT do not have enough functional hemoglobin in their red blood cells and require regular, lifelong blood transfusions, often beginning early in childhood, along with ongoing iron chelation therapy. While transfusions are necessary for survival, many of the long‑term complications of TDT are exacerbated by chronic transfusion therapy and iron overload and cumulative damage to the heart, liver and endocrine system, as well as bone abnormalities and delayed growth and puberty. TDT places a significant and ongoing burden on patients and their families, requiring frequent medical visits and complex lifelong treatment. Despite lifelong treatment, people with TDT in the U.S. face shortened life expectancy, with a median age of death of approximately 37 years, reduced quality of life and productivity, and the estimated lifetime healthcare costs of managing the disease are $5–5.7 million. About CASGEVY ® (exagamglogene autotemcel) CASGEVY is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy for eligible patients with SCD or TDT, in which a patient’s own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene through a precise double-strand break. This edit results in the production of high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. CASGEVY has been shown in clinical trials to reduce or eliminate VOCs for patients with SCD and transfusion requirements for patients with TDT. In the United States, CASGEVY was approved using the Commissioner’s National Priority Voucher. Vertex has also recently completed regulatory submissions in the Kingdom of Saudi Arabia and United Kingdom to expand the use of CASGEVY to children as young as five. About the CLIMB Studies The completed Phase 1/2/3 open-label studies, CLIMB-111 and CLIMB-121, were designed to assess the safety and efficacy of a single dose of CASGEVY in patients ages 12-35 years with TDT or with SCD and recurrent VOCs. Patients were followed for approximately two years after CASGEVY infusion in these studies. CLIMB-141 and CLIMB-151 are ongoing Phase 3 open-label studies, designed to assess the safety and efficacy of a single dose of exagamglogene autotemcel in patients ages 2-11 years with TDT or with SCD and recurrent VOCs. Enrollment and dosing are complete for the 5–11-year-old cohort in both studies. Each patient in these studies is asked to participate in the ongoing long-term, open-label study, CLIMB-131. CLIMB-131 is designed to evaluate the long-term safety and efficacy of CASGEVY in patients with up to 15 years of follow up after CASGEVY infusion. U.S. INDICATIONS AND IMPORTANT SAFETY INFORMATION FOR CASGEVY INDICATION CASGEVY is indicated for the treatment of patients aged 2 years and older with: sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) transfusion-dependent β-thalassemia (TDT) IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Neutrophil Engraftment Failure There is potential risk of neutrophil engraftment failure after treatment with CASGEVY. In the clinical trials, all treated patients achieved neutrophil engraftment and no patients received rescue CD34 + cells. Monitor absolute neutrophil counts (ANC) and manage infections according to standard guidelines and medical judgement. In the event of neutrophil engraftment failure, patients should be infused with rescue CD34 + cells. Granulocyte colony-stimulating factor (G-CSF) is not recommended for 21 days after CASGEVY infusion. Delayed Platelet Engraftment Delayed platelet engraftment has been observed with CASGEVY treatment. There is an increased risk of bleeding until platelet engraftment is achieved. Monitor patients for bleeding according to standard guidelines and medical judgement. Conduct frequent platelet counts until platelet engraftment and platelet recovery are achieved. Perform blood cell count determination and other appropriate testing whenever clinical symptoms suggestive of bleeding arise. Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis can occur due to dimethyl sulfoxide (DMSO) or dextran 40 in the cryopreservation solution. Monitor patients for hypersensitivity reactions during and after infusion. Off-Target Genome Editing Risk The risk of unintended, off-target editing in an individual’s CD34 + cells cannot be ruled out due to genetic variants. The clinical significance of potential off-target editing is unknown. ADVERSE REACTIONS The most common Grade 3 or 4 non‑laboratory adverse reactions (occurring in ≥ 25%) were mucositis and febrile neutropenia in patients with SCD and patients with TDT, and decreased appetite in patients with SCD. All (100%) of the patients with TDT and SCD experienced Grade 3 or 4 neutropenia and thrombocytopenia. Other common Grade 3 or 4 laboratory abnormalities (≥ 50%) include leukopenia, anemia, and lymphopenia. DRUG INTERACTIONS No formal drug interaction studies have been performed. CASGEVY is not expected to interact with the hepatic cytochrome P450 family of enzymes or drug transporters. Use of Granulocyte-Colony Stimulating Factor (G-CSF): G-CSF must not be used for CD34 + HSC mobilization of patients with SCD. Use of Hydroxyurea: Discontinue the use of hydroxyurea at least 8 weeks prior to start of each mobilization cycle and conditioning. There is no experience of the use of hydroxyurea after CASGEVY infusion. Use of Crizanlizumab: Discontinue the use of crizanlizumab at least 8 weeks prior to start of mobilization and conditioning, as their interaction potential with mobilization and myeloablative conditioning agents is not known. Use of Iron Chelators: Discontinue the use of iron chelators at least 7 days prior to initiation of myeloablative conditioning, due to potential interaction with the conditioning agent. Some iron chelators are myelosuppressive. If iron chelation is required, avoid the use of non-myelosuppressive iron chelators for at least 3 months and use of myelosuppressive iron chelators for at least 6 months after CASGEVY infusion. Phlebotomy can be used instead of iron chelation, when appropriate. USE IN SPECIFIC POPULATIONS Pregnancy/Lactation: CASGEVY must not be administered during pregnancy and breastfeeding should be discontinued during conditioning because of the risks associated with myeloablative conditioning. Pregnancy and breastfeeding after CASGEVY infusion should be discussed with the treating physician. Females and Males of Reproductive Potential: A negative serum pregnancy test must be confirmed prior to the start of each mobilization cycle and reconfirmed prior to myeloablative conditioning. Women of childbearing potential and men capable of fathering a child should use effective methods of contraception from start of mobilization through at least 6 months after administration of CASGEVY. Advise patients of the risks associated with conditioning agents. Infertility has been observed with myeloablative conditioning, therefore, advise patients of fertility preservation options before treatment, if appropriate. Please see full Prescribing Information for CASGEVY. About Vertex Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases and conditions. The company has approved therapies for cystic fibrosis, sickle cell disease, transfusion-dependent beta thalassemia and acute pain, and it continues to advance clinical and research programs in these areas. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including IgA nephropathy, neuropathic pain, APOL1-mediated kidney disease, primary membranous nephropathy, autosomal dominant polycystic kidney disease, type 1 diabetes, generalized myasthenia gravis, and myotonic dystrophy type 1. Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry's top places to work, including 16 consecutive years on Science magazine's Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex's history of innovation, visit or follow us on LinkedIn , Facebook , Instagram , YouTube and X . Special Note Regarding Forward-Looking Statements This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, statements made by Reshma Kewalramani, M.D., and Haydar Frangoul, M.D., M.S., in this press release, statements regarding the expected clinical benefits of CASGEVY, expectations regarding the eligible patient population, and expectations for patient access to CASGEVY. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include the risks listed under the heading “Risk Factors” in Vertex's annual report and in subsequent filings filed with the Securities and Exchange Commission at and available through the company's website at . You should not place undue reliance on these statements. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available. (VRTX-GEN) Contacts Vertex Pharmaceuticals Incorporated Investors: InvestorInfo@vrtx.com or +1 617-341-6108 Media: mediainfo@vrtx.com or 617-341-6992

2026-06-03

·药增长

辉瑞$105亿签下12个中国ADC，信达一夜进账$6.5亿——美国国会坐不住了

辉瑞以$6.5亿首付+最高$98.5亿里程碑，签下信达生物12个肿瘤管线——这是继BMS恒瑞$150亿后，美资药企对中国biotech的又一次百亿级押注。Coinbase创始人Brian Armstrong的抗衰老公司NewLimit，拿了$4.35亿C轮，估值冲到$31亿，药还没进临床。礼来一周签三单，总潜在$50亿，同时对340B医院发出"不交数据就停折扣"的最后通牒。Fulcrum因为FDA一纸判决，镰状细胞药扑街，市值跌了50%，开始"卖身"。写在前面这周医药圈有三条线。一条是大钱的方向——辉瑞和信达的$105亿交易，让"中国管线+美国商业化"的公式彻底成型。一条是"不老药"的赌注——NewLimit的$4.35亿C轮，投的不是药，是一个还没进临床的想法。还有一条是输家的故事——Fulcrum被FDA一纸判决判了死刑，Praxis的癫痫药III期扑街，股价双位数崩跌。每一笔交易背后，都是资源对"可能性和确定性"的重新定价。一、辉瑞×信达：$105亿，12个ADC/双抗，中国管线成了硬通货这笔交易有多大？ 5月29日，辉瑞和信达生物宣布达成全球战略合作，围绕12个肿瘤早期项目。信达生物收到$6.5亿首付款，潜在里程碑最高$98.5亿，总交易规模高达$105亿。 12个项目涵盖8个信达自有早期管线和4个辉瑞提议的全新项目，聚焦ADC和多特异性抗体。交易结构分三层： 4个全球独家授权辉瑞——辉瑞承担全球开发成本 4个大中华区外授权辉瑞——辉瑞承担大部分开发成本 4个全球联合开发/商业化——双方分利润信达负责把管线推进到I期临床，之后辉瑞主导全球开发。这不是一锤子买卖。Jeff Legos，辉瑞肿瘤学首席官，在公告中说了一句话："结合信达的发现和早期临床能力与辉瑞的全球研发和商业化能力，我们有机会加速交付能重新定义治疗标准的突破。" 翻译成人话：辉瑞缺早期管线，中国有。为什么这比交易比表面看起来更大？放在一个更大的图景里看： 2025年以来，GSK（$8B+）、Takeda、阿斯利康、礼来、BMS（$150B恒瑞）和辉瑞（$105B信达），6家跨国药企先后跟中国biotech签了百亿级多药合作协议。信达一家就参与了其中3个——加起来潜在收入超过$300亿。 BioPharma Dive的数据显示，2025年全年超过60笔中国药企对外授权交易，2026年已有超过25笔。彭博社直接说：这些交易表明"中国制药企业已发展成为全球新药研发的重要增长极"。但美国国内没那么平静。STAT News 5月18日的报道标题是"Biotech行业在中国药上分裂了：机会还是生存威胁？"一些美国biotech创始人和投资人公开表达担忧——中国管线正在"吃掉"本该属于美国早期创新的资本和注意力。如果你是中国biotech投资者或从业者——信达这笔交易给出了一个路线图：早期资产+高质量数据=I期后就能变现。如果你在跨国药企做BD——不进中国扫货，竞争对手已经在扫了。辉瑞肿瘤学过去几年一直在补管线，Seagen的收购只是第一步。信达这笔交易，是第二步。来源：BioPharma Dive: https://www.biopharmadive.com/news/pfizerinnoventchinaadccancerdrugdeal/821444/ 辉瑞官网: https://www.pfizer.com/news/pressrelease/pressreleasedetail/pfizerandinnoventbiologicsenterglobalstrategic 二、NewLimit的$4.35亿：连老鼠数据都没有，"长寿"两个字值$31亿谁在投？ 6月3日，抗衰老初创NewLimit宣布完成$4.35亿C轮融资，Founders Fund领投，Thrive Capital、Greenoaks、Quiet Capital和礼来风投跟投。投后估值约$31亿。这是2026年生物科技领域最大的风投轮次之一。 NewLimit成立于2021年，创始人是Coinbase CEO Brian Armstrong、前GV合伙人Blake Byers和干细胞生物学家Jacob Kimmel。公司核心是"表观遗传重编程"——简单说，就是通过改变细胞的身份标记，让衰老细胞"返老还童"。但这家公司还没启动第一个临床试验。CEO Kimmel说，计划2027年启动首个肝重编程疗法的人体试验。这个估值疯狂吗？一年内，NewLimit融了三轮：2025年5月$1.3亿B轮，10月再追$4500万，现在$4.35亿C轮。加起来超过$6亿——没有临床数据，没有动物数据公开发表。但这恰恰是新资本逻辑的体现。Founders Fund的Peter Thiel一直公开表达对"抗衰老"的兴趣，Thrive Capital的Josh Kushner也把长寿列为重点赛道。这轮融资的逻辑不是"赌这个药能成药"，而是"赌这个方向值$31亿的入场券"。有意思的是，礼来风投也参与了。礼来今年在减肥药上赚了太多现金（一季度营收增长56%），正在四处撒网——从RNA编辑到抗衰老到GLP2，什么都投。如果NewLimit成功，它改写的不是一种病，而是"衰老"这个最大的未被定义的适应症。如果失败，$6亿将成为生物科技史上最贵的"想法验证"之一。来源：https://www.statnews.com/2026/06/02/longevitystartupnewlimitannounces435millionclinicaltrialfinancing/ BioPharma Dive: https://www.biopharmadive.com/news/newlimitlillyhanmihaiscopraxiscytomxregeneron/821624/ 三、礼来一周签三单：$50亿铺开减肥、中国管线、药物递送礼来在买什么？ 6月2日，礼来一口气宣布了三笔交易： 1. Hanmi Pharmaceutical（韩国）：获得GLP2类似物减肥药sonefpeglutide的全球权益。GLP2靶点不同于GLP1——它可能解决减重后"反弹"的问题。 2. 海思科（中国）：获得最多5个未公开管线的权益，横跨多个治疗领域。 3. Camurus（瑞典）：扩大现有合作，获得药物递送技术的更多权益。三笔交易潜在总金额近$50亿。礼来今年的交易速度令人咋舌——从Kelonia的$32亿收购到现在的三连签，几乎是一周一单。但礼来同时在收紧另一只手同一天，礼来对参与340B药品折扣计划的医院发出了最后通牒：下周一之前交出所有礼来药品的处方报销数据，否则停止340B折扣。 340B是美国联邦计划，要求药企给服务弱势群体的医院提供折扣价。礼来说有些医院在"双重吃折扣"——既拿340B折扣又在Medicaid报销。医院说礼来在非法限缩340B。这场仗不只是礼来在打。诺和诺德今年也推出了类似政策。药企在340B上的总折扣从2021年的$440亿涨到了2025年超过$600亿。礼来的Josh O'Harra在给HHS的信里写道："我们不能让一小撮医院协会阻止一个合法、温和的诚信措施。" 但医院的340B Health CEO Maureen Testoni反击说："如果联邦政府不出手，数百家其他药企也会跟进，大幅增加那些服务弱势患者医院的成本。" 说白了：礼来一手从减肥药赚现金，一手捏住340B的成本端，同时在管线端激进下注。这种打法，只有现金流极度充裕时才能玩。来源： BioPharma Dive: https://www.biopharmadive.com/news/newlimitlillyhanmihaiscopraxiscytomxregeneron/821624/ > BioPharma Dive: https://www.biopharmadive.com/news/elililly340bhospitalultimatumdatasharinghrsa/821744/ 四、Fulcrum：FDA一句话，$3亿市值没了，开始"卖身" 发生了什么？ 6月3日，Fulcrum Therapeutics宣布，其镰状细胞病药物pociredir的开发被彻底终止。原因是FDA在最近的会议记录中得出结论：pociredir的安全性风险太大，"没有可行的监管路径"。关键问题出在PRC2抑制剂这个药物类别上。Ipsen的Tazverik（同靶点药物）3月被撤市，因为在长期随访中发现了高于预期的继发性血液癌症。 Fulcrum争辩说pociredir虽然也抑制PRC2，但结合位点不同，不应该有同样的安全风险。临床数据也确实没看到新的安全信号。但FDA的态度是：不管你机制细节如何，PRC2抑制剂作为一个类别，先亮红灯。 Fulcrum股价一天跌了超50%，现在每股$3出头。CEO Alex Sapir说公司正在"探索战略替代方案"，包括出售资产或整体卖身。公司也在大幅削减运营成本。截至3月31日，账上还有约$3.3亿现金。 Leerink分析师Joseph Schwartz把评级直接降到"观望"，但特意说了一句耐人寻味的话："我们对这个结果感到意外"——因为临床数据本身没有负面信号。镰状细胞病这个赛道，近年来几乎是个"墓园"。2023年，Intellia、Sangamo、Graphite Bio三家的镰状细胞基因疗法相继终止。2024年，辉瑞把花$54亿收购Global Blood得来的Oxbryta因安全问题撤市。2025年，辉瑞和Agios各自的镰状细胞药数据都不理想。诺华的Adakveo也被欧洲撤市。这条赛道，几乎没有一个玩家活得舒服。Fulcrum只是最新的一个。来源：BioPharma Dive: https://www.biopharmadive.com/news/fulcrumstrategicreviewsicklecellfdapociredir/821740/

100 项与 Crizanlizumab-TMCA 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11480	Crizanlizumab-TMCA	B06AX01	DB15271

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
镰状细胞血症	美国	Novartis Pharmaceuticals Corp.	2019-11-15
血管闭塞危机	美国	Novartis Pharmaceuticals Corp.	2019-11-15

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
镰状细胞遗传性状	临床3期	荷兰	Novartis Pharma AG	2021-05-03
新型冠状病毒感染	临床2期	美国	Novartis AG	2020-07-09
阴茎异常勃起	临床2期	美国	Novartis Pharmaceuticals Corp.	2019-10-16
骨髓纤维化	临床2期	澳大利亚	Novartis Pharmaceuticals Corp.	2019-09-26
骨髓纤维化	临床2期	加拿大	Novartis Pharmaceuticals Corp.	2019-09-26
骨髓纤维化	临床2期	丹麦	Novartis Pharmaceuticals Corp.	2019-09-26
骨髓纤维化	临床2期	德国	Novartis Pharmaceuticals Corp.	2019-09-26
骨髓纤维化	临床2期	匈牙利	Novartis Pharmaceuticals Corp.	2019-09-26
骨髓纤维化	临床2期	意大利	Novartis Pharmaceuticals Corp.	2019-09-26
骨髓纤维化	临床2期	荷兰	Novartis Pharmaceuticals Corp.	2019-09-26

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临床结果

适应症

分期

评价

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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


NCT06439082 (SPARKLE, ASH2025)	临床3期	镰状细胞血症	315	Crizanlizumab 5.0 mg/kg	淵膚選觸顧獵鏇鹹壓鏇(憲顧鬱製廠製範遞鏇壓) = 觸壓膚選糧觸鑰繭築顧鹽淵願積遞築簾蓋鑰夢 (艱鑰鹹鹽願衊製餘鹹鹹 ) 更多	积极	2025-12-06
				Placebo	淵膚選觸顧獵鏇鹹壓鏇(憲顧鬱製廠製範遞鏇壓) = 膚構鹽構選壓襯顧壓顧鹽淵願積遞築簾蓋鑰夢 (艱鑰鹹鹽願衊製餘鹹鹹 ) 更多
PS2172 (EHA2025)	N/A	P-selectin	994	Crizanlizumab (Complete biologic responders)	顧範夢蓋願廠廠鏇鹹構(齋膚膚憲積艱範齋餘製) = 鹽選膚廠獵積選衊獵顧衊遞繭選襯蓋鬱廠糧夢 (壓膚膚夢鹹鹹鹹顧鏇製 )	积极	2025-05-14
				Crizanlizumab (Incomplete biologic responders)	顧範夢蓋願廠廠鏇鹹構(齋膚膚憲積艱範齋餘製) = 繭餘觸糧膚構製網憲淵衊遞繭選襯蓋鬱廠糧夢 (壓膚膚夢鹹鹹鹹顧鏇製 )
NCT03814746 (STAND, Pubmed) 人工标引	临床3期	镰状细胞血症	252	crizanlizumabcrizanlizumab 5.0 mg/kg	積醖遞醖襯選糧鹹齋餘(壓繭觸鑰鹽衊蓋網壓艱) = 築窪製淵築築簾願窪廠觸觸糧餘鹽糧顧獵蓋簾 (艱夢鑰簾蓋襯夢齋鹹鹹, 1.90 ~ 3.26) 更多	不佳	2025-04-01
				crizanlizumabcrizanlizumab 7.5 mg/kg	積醖遞醖襯選糧鹹齋餘(壓繭觸鑰鹽衊蓋網壓艱) = 鹹襯壓製獵願醖壓範顧觸觸糧餘鹽糧顧獵蓋簾 (艱夢鑰簾蓋襯夢齋鹹鹹, 1.56 ~ 2.65) 更多
NCT03938454 (SPARTAN, CTgov)	临床2期	阴茎异常勃起 \| 镰状细胞血症	36	Crizanlizumab	鑰選壓餘醖鏇壓顧願構(網艱範憲鬱構顧夢鏇構) = 糧醖鹽積壓積夢選窪憲齋鏇鹹艱觸積顧製壓簾 (餘窪襯糧餘壓築鹹築構, 膚壓觸膚膚顧膚憲夢願 ~ 醖選鬱廠製遞淵壓獵願) 更多	-	2025-03-10
NCT04662931 (CTgov)	临床4期	血管闭塞危机 \| 镰状细胞血症	140	Crizanlizumab	鑰憲鹽簾願鹹遞糧鹹壓 = 餘蓋糧膚壓蓋鏇積淵糧艱夢網鏇廠鹽遞齋廠廠 (獵築糧壓醖憲鬱簾構衊, 襯構獵遞製壓鹽獵鑰選 ~ 鏇膚艱鏇廠憲構遞觸遞) 更多	-	2025-01-08
ASH2024	N/A	镰状细胞血症	-	Crizanlizumab 5.0 mg/kg	鹽簾網範襯選觸簾鑰獵(艱窪齋廠餘衊願廠築窪) = 製齋鏇繭壓積範繭鏇齋鏇遞觸製遞範鑰夢繭窪 (膚糧願膚選糧艱憲襯糧 ) 更多	-	2024-12-07
				Crizanlizumab 8.5 mg/kg	鹽簾網範襯選觸簾鑰獵(艱窪齋廠餘衊願廠築窪) = 壓鏇觸餘遞壓廠繭餘壓鏇遞觸製遞範鑰夢繭窪 (膚糧願膚選糧艱憲襯糧 ) 更多
NCT04611880 (Pubmed \| J Clin Invest)	临床2期	伴脑白质营养不良的视网膜血管病变 exonuclease 3 prime repair exonuclease 1 (TREX1) mutations	11	Crizanlizumab	壓願選選膚夢齋夢艱網(艱積鬱鹽構鏇簾糧鏇獵) = 8 of 11 (72.7%) reporting mild adverse effects such as nausea, fatigue, and gastrointestinal symptoms 淵鹽鬱窪鏇顧蓋鬱積鑰 (鬱鏇鏇繭艱艱齋選鬱繭 )	积极	2024-06-17
ARVO2024	临床2期	伴脑白质营养不良的视网膜血管病变	10	Crizanlizumab 5 mg/kg	簾鹽壓壓夢積夢觸糧積(窪齋選艱醖觸獵膚獵構) = No patients experienced severe adverse events, with mild to moderate events attributed to constitutional symptoms (48%) or gastrointestinal symptoms (35%). 廠鑰構網襯選製願顧醖 (醖鹽簾膚壓製齋鹹襯鑰 )	积极	2024-05-05
NCT03264989 (SOLACE-adults, CTgov)	临床2期	镰状细胞血症	57	Crizanlizumab (Crizanlizumab 5.0 mg/kg)	夢窪願構獵鹽艱齋衊窪(鏇製鬱築艱選廠網壓壓) = 鬱蓋願淵鑰網顧簾壓廠鹹鹹憲衊鹽顧壓選範獵 (範簾膚鏇憲遞夢糧襯製, 2810) 更多	-	2024-04-23
				Crizanlizumab (Crizanlizumab 7.5 mg/kg)	膚膚膚範鬱繭餘廠製獵(構壓蓋餘顧築願構齋築) = 糧餘網鹹繭構蓋構鏇選遞餘鏇糧構積壓構齋餘 (獵積衊製鬱築夢顧膚製, 願膚簾醖簾構憲網網繭 ~ 夢淵獵獵憲積衊襯艱獵) 更多
NCT03814746 (STAND, CTgov)	临床3期	镰状细胞血症	254	Crizanlizumab (SEG101) (Crizanlizumab (SEG101) at 5.0 mg/kg)	醖齋襯憲鑰鏇觸膚鏇壓(壓淵醖餘廠構鬱積淵築) = 製觸鹽廠積窪鬱遞顧淵繭壓膚膚遞襯鹽窪鏇鹽 (網齋糧齋築簾襯觸衊網, 2.98) 更多	-	2024-01-08
				Crizanlizumab (Crizanlizumab (SEG101) at 7.5 mg/kg)	醖齋襯憲鑰鏇觸膚鏇壓(壓淵醖餘廠構鬱積淵築) = 齋積餘鹽糧鹽餘糧衊憲繭壓膚膚遞襯鹽窪鏇鹽 (網齋糧齋築簾襯觸衊網, 2.30) 更多