Sutimlimab
目录号 : GC66348
Sutimlimab 是首创的补体蛋白成分 1，s 亚成分 (C1s)抑制剂，可用于冷凝集素综合征的研究。C1s 是一种丝氨酸蛋白酶，可切割 C4 和 C2 以形成 C3 转化酶。
Cas No.:2049079-64-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Sutimlimab, a first-in-class complement protein component 1, s subcomponent (C1s) inhibitor, can be used for the research of cold agglutinin disease. C1s is a serine protease which cleaves C4 and C2 to form the C3 convertase[1].
| Cas No. | 2049079-64-1 | SDF | Download SDF |
| 分子式 | 分子量 | ||
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Sutimlimab in Cold Agglutinin Disease
N Engl J Med 2021 Apr 8;384(14):1323-1334.PMID:33826820DOI:10.1056/NEJMoa2027760.
Background: Cold agglutinin disease is a rare autoimmune hemolytic anemia characterized by hemolysis that is caused by activation of the classic complement pathway. Sutimlimab, a humanized monoclonal antibody, selectively targets the C1s protein, a C1 complex serine protease responsible for activating this pathway. Methods: We conducted a 26-week multicenter, open-label, single-group study to assess the efficacy and safety of intravenous Sutimlimab in patients with cold agglutinin disease and a recent history of transfusion. The composite primary end point was a normalization of the hemoglobin level to 12 g or more per deciliter or an increase in the hemoglobin level of 2 g or more per deciliter from baseline, without red-cell transfusion or medications prohibited by the protocol. Results: A total of 24 patients were enrolled and received at least one dose of Sutimlimab; 13 patients (54%) met the criteria for the composite primary end point. The least-squares mean increase in hemoglobin level was 2.6 g per deciliter at the time of treatment assessment (weeks 23, 25, and 26). A mean hemoglobin level of more than 11 g per deciliter was maintained in patients from week 3 through the end of the study period. The mean bilirubin levels normalized by week 3. A total of 17 patients (71%) did not receive a transfusion from week 5 through week 26. Clinically meaningful reductions in fatigue were observed by week 1 and were maintained throughout the study. Activity in the classic complement pathway was rapidly inhibited, as assessed by a functional assay. Increased hemoglobin levels, reduced bilirubin levels, and reduced fatigue coincided with inhibition of the classic complement pathway. At least one adverse event occurred during the treatment period in 22 patients (92%). Seven patients (29%) had at least one serious adverse event, none of which were determined by the investigators to be related to Sutimlimab. No meningococcal infections occurred. Conclusions: In patients with cold agglutinin disease who received Sutimlimab, selective upstream inhibition of activity in the classic complement pathway rapidly halted hemolysis, increased hemoglobin levels, and reduced fatigue. (Funded by Sanofi; CARDINAL ClinicalTrials.gov number, NCT03347396.).
Sutimlimab: First Approval
Drugs 2022 May;82(7):817-823.PMID:35412113DOI:10.1007/s40265-022-01711-5.
Sutimlimab (sutimlimab-jome; ENJAYMO™) is a humanized monoclonal antibody developed by Sanofi for the treatment of cold agglutinin disease (CAD). Sutimlimab is an immunoglobulin G, subclass 4 (IgG4) monoclonal antibody that inhibits the classical complement pathway by binding to complement protein component 1, s subcomponent (C1s), a serine protease which cleaves C4 and C2 to form the C3 convertase. Inhibition of the classical complement pathway at the level of C1s prevents deposition of complement opsonins on the surface of red blood cell (RBCs), leading to inhibition of haemolysis in patients with CAD. In February 2022, Sutimlimab received its first approval in the USA to decrease the need for RBC transfusion due to haemolysis in adults with CAD. Sutimlimab is under regulatory review in Japan and the EU for CAD. This article summarizes the milestones in the development of Sutimlimab leading to this first approval for CAD.
Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial
Blood 2022 Sep 1;140(9):980-991.PMID:35687757DOI:10.1182/blood.2021014955.
Sutimlimab, a first-in-class humanized immunoglobulin G4 (IgG4) monoclonal antibody that selectively inhibits the classical complement pathway at C1s, rapidly halted hemolysis in the single-arm CARDINAL study in recently transfused patients with cold agglutinin disease (CAD). CADENZA was a 26-week randomized, placebo-controlled phase 3 study to assess safety and efficacy of Sutimlimab in patients with CAD without recent (within 6 months prior to enrollment) transfusion history. Forty-two patients with screening hemoglobin ≤10 g/dL, elevated bilirubin, and ≥1 CAD symptom received Sutimlimab (n = 22) or placebo (n = 20) on days 0 and 7 and then biweekly. Composite primary endpoint criteria (hemoglobin increase ≥1.5 g/dL at treatment assessment timepoint [mean of weeks 23, 25, 26], avoidance of transfusion, and study-prohibited CAD therapy [weeks 5-26]) were met by 16 patients (73%) on Sutimlimab, and 3 patients (15%) on placebo (odds ratio, 15.9 [95% confidence interval, 2.9, 88.0; P < .001]). Sutimlimab, but not placebo, significantly increased mean hemoglobin and FACIT-Fatigue scores at treatment assessment timepoint. Sutimlimab normalized mean bilirubin by week 1. Improvements correlated with near-complete inhibition of the classical complement pathway (2.3% mean activity at week 1) and C4 normalization. Twenty-one (96%) Sutimlimab patients and 20 (100%) placebo patients experienced ≥1 treatment-emergent adverse event. Headache, hypertension, rhinitis, Raynaud phenomenon, and acrocyanosis were more frequent with Sutimlimab vs placebo, with a difference of ≥3 patients between groups. Three Sutimlimab patients discontinued owing to adverse events; no placebo patients discontinued. These data demonstrate that Sutimlimab has potential to be an important advancement in the treatment of CAD. This trial was registered at www.clinicaltrials.gov as #NCT03347422.
Sutimlimab for treatment of cold agglutinin disease: why, how and for whom?
Immunotherapy 2022 Oct;14(15):1191-1204.PMID:35946351DOI:10.2217/imt-2022-0085.
Therapies for cold agglutinin disease have been directed at the pathogenic B-cell clone. Sutimlimab, a monoclonal antibody that targets C1s, is the first complement inhibitor to be extensively studied in cold agglutinin disease. Sutimlimab selectively blocks the classical activation pathway and leaves the alternative and lectin pathways intact. Trials have documented high response rates with rapid improvement in hemolysis, hemoglobin levels and fatigue scores and low toxicity. Sutimlimab was recently approved in the USA. This drug appears to be particularly useful in severely anemic patients who require a rapid response, in acute exacerbations that do not resolve spontaneously and in patients in whom chemoimmunotherapy is contraindicated or has failed. The choice of therapy in cold agglutinin disease should be individualized.
Sutimlimab: A Complement C1s Inhibitor for the Management of Cold Agglutinin Disease-Associated Hemolysis
Ann Pharmacother 2022 Dec 8;10600280221138802.PMID:36476151DOI:10.1177/10600280221138802.
Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, dosing and administration, and place in therapy of Sutimlimab for the management of cold agglutinin disease (CAD)-associated hemolysis. Data sources: A literature search of PubMed (1966-October 2022) was conducted using the keywords Sutimlimab, BIVV009, and cold agglutinin. Data were also obtained from prescribing information, meeting abstracts, and clinicaltrials.gov. Study selection and data extraction: All published prospective clinical trials, prescribing information, and meeting abstracts on Sutimlimab for the treatment of CAD were reviewed. Data synthesis: Sutimlimab is a first-in-class complement C1s inhibitor indicated for the treatment of CAD-associated hemolysis. This approval was based on the phase III CARDINAL trial, which evaluated Sutimlimab in patients with CAD-associated hemolysis. The primary endpoint of achieving a hemoglobin of ≥12 g/dL or increase of ≥2 above baseline was achieved by 54% of patients with Sutimlimab in the 26-week trial. The phase III CADENZA trial was a placebo-controlled trial in which Sutimlimab has demonstrated a significant improvement in the composite endpoint of hemoglobin increase of ≥1.5 g/dL, avoidance of transfusion, and avoidance of additional CAD therapies (73% Sutimlimab vs 15% placebo). Relevance to patient care and clinical practice in comparison with existing drugs: Sutimlimab rapidly halts hemolysis, improves hemoglobin, and improves quality-of-life in patients with CAD. Safety issues with Sutimlimab include infusion-related reactions and risk of serious infections with encapsulated bacteria. Conclusions: Sutimlimab provides an additional therapeutic option in the treatment of CAD-associated hemolysis that can lead to rapid improvement in hemoglobin and anemia-related symptoms.