Caplacizumab
(Synonyms: ALX-0681; ALX-0081) 目录号 : GC68345Caplacizumab (Cablivi) 是一种人源化抗血管性血友病因子 (vWF) 纳米抗体。Caplacizumab 抑制 vWF 介导的血小板粘附并防止进一步的微血栓形成。Caplacizumab 可用于血栓性血小板减少性紫癜（TTP）的研究。
Cas No.:915810-67-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Caplacizumab (Cablivi) is a humanized anti-von Willebrand factor (vWF) nanobody. Caplacizumab inhibits the vWF-mediated platelet adhesion and prevents further microthrombi formation. Caplacizumab can be used for the research of thrombotic thrombocytopenic purpura (TTP)[1].
[1]. MaËlle le Besnerais, et al. Caplacizumab: a change in the paradigm of thrombotic thrombocytopenic purpura treatment. Expert Opin Biol Ther. 2019 Nov;19(11):1127-1134.
| Cas No. | 915810-67-2 | SDF | Download SDF |
| 别名 | ALX-0681; ALX-0081 | ||
| 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。 | ||
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| 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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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。
Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura
N Engl J Med 2019 Jan 24;380(4):335-346.PMID:30625070DOI:10.1056/NEJMoa1806311.
Background: In acquired thrombotic thrombocytopenic purpura (TTP), an immune-mediated deficiency of the von Willebrand factor-cleaving protease ADAMTS13 allows unrestrained adhesion of von Willebrand factor multimers to platelets and microthrombosis, which result in thrombocytopenia, hemolytic anemia, and tissue ischemia. Caplacizumab, an anti-von Willebrand factor humanized, bivalent variable-domain-only immunoglobulin fragment, inhibits interaction between von Willebrand factor multimers and platelets. Methods: In this double-blind, controlled trial, we randomly assigned 145 patients with TTP to receive Caplacizumab (10-mg intravenous loading bolus, followed by 10 mg daily subcutaneously) or placebo during plasma exchange and for 30 days thereafter. The primary outcome was the time to normalization of the platelet count, with discontinuation of daily plasma exchange within 5 days thereafter. Key secondary outcomes included a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the trial treatment period; recurrence of TTP at any time during the trial; refractory TTP; and normalization of organ-damage markers. Results: The median time to normalization of the platelet count was shorter with Caplacizumab than with placebo (2.69 days [95% confidence interval {CI}, 1.89 to 2.83] vs. 2.88 days [95% CI, 2.68 to 3.56], P=0.01), and patients who received Caplacizumab were 1.55 times as likely to have a normalization of the platelet count as those who received placebo. The percentage of patients with a composite outcome event was 74% lower with Caplacizumab than with placebo (12% vs. 49%, P<0.001). The percentage of patients who had a recurrence of TTP at any time during the trial was 67% lower with Caplacizumab than with placebo (12% vs. 38%, P<0.001). Refractory disease developed in no patients in the Caplacizumab group and in three patients in the placebo group. Patients who received Caplacizumab needed less plasma exchange and had a shorter hospitalization than those who received placebo. The most common adverse event was mucocutaneous bleeding, which was reported in 65% of the patients in the Caplacizumab group and in 48% in the placebo group. During the trial treatment period, three patients in the placebo group died. One patient in the Caplacizumab group died from cerebral ischemia after the end of the treatment period. Conclusions: Among patients with TTP, treatment with Caplacizumab was associated with faster normalization of the platelet count; a lower incidence of a composite of TTP-related death, recurrence of TTP, or a thromboembolic event during the treatment period; and a lower rate of recurrence of TTP during the trial than placebo. (Funded by Ablynx; HERCULES ClinicalTrials.gov number, NCT02553317 .).
Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura
N Engl J Med 2016 Feb 11;374(6):511-22.PMID:26863353DOI:10.1056/NEJMoa1505533.
Background: Acquired thrombotic thrombocytopenic purpura (TTP) is caused by aggregation of platelets on ultralarge von Willebrand factor multimers. This microvascular thrombosis causes multiorgan ischemia with potentially life-threatening complications. Daily plasma exchange and immunosuppressive therapies induce remission, but mortality and morbidity due to microthrombosis remain high. Methods: Caplacizumab, an anti-von Willebrand factor humanized single-variable-domain immunoglobulin (Nanobody), inhibits the interaction between ultralarge von Willebrand factor multimers and platelets. In this phase 2, controlled study, we randomly assigned patients with acquired TTP to subcutaneous Caplacizumab (10 mg daily) or placebo during plasma exchange and for 30 days afterward. The primary end point was the time to a response, defined as confirmed normalization of the platelet count. Major secondary end points included exacerbations and relapses. Results: Seventy-five patients underwent randomization (36 were assigned to receive Caplacizumab, and 39 to receive placebo). The time to a response was significantly reduced with Caplacizumab as compared with placebo (39% reduction in median time, P=0.005). Three patients in the Caplacizumab group had an exacerbation, as compared with 11 patients in the placebo group. Eight patients in the Caplacizumab group had a relapse in the first month after stopping the study drug, of whom 7 had ADAMTS13 activity that remained below 10%, suggesting unresolved autoimmune activity. Bleeding-related adverse events, most of which were mild to moderate in severity, were more common with Caplacizumab than with placebo (54% of patients vs. 38%). The frequencies of other adverse events were similar in the two groups. Two patients in the placebo group died, as compared with none in the Caplacizumab group. Conclusions: Caplacizumab induced a faster resolution of the acute TTP episode than did placebo. The platelet-protective effect of Caplacizumab was maintained during the treatment period. Caplacizumab was associated with an increased tendency toward bleeding, as compared with placebo. (Funded by Ablynx; ClinicalTrials.gov number, NCT01151423.).
Real-world experience with Caplacizumab in the management of acute TTP
Blood 2021 Apr 1;137(13):1731-1740.PMID:33150355DOI:10.1182/blood.2020007599.
The cornerstone of life-saving therapy in immune-mediated thrombotic thrombocytopenic purpura (iTTP) has been plasma exchange (PEX) combined with immunomodulatory strategies. Caplacizumab, a novel anti-von Willebrand factor nanobody trialed in 2 multicenter randomized controlled trials (RCTs) leading to European Union and US Food and Drug Administration approval, has been available in the United Kingdom (UK) through a patient access scheme. Data were collected retrospectively from 2018 to 2020 for 85 patients (4 children) receiving Caplacizumab from 22 UK hospitals. Patient characteristics and outcomes in the real-world clinical setting were compared with Caplacizumab trial end points and historical outcomes in the precaplacizumab era. Eighty-four of 85 patients received steroid and rituximab alongside PEX; 26% required intubation. Median time to platelet count normalization (3 days), duration of PEX (7 days), and hospital stay (12 days) were comparable with RCT data. Median duration of PEX and time from PEX initiation to platelet count normalization were favorable compared with historical outcomes (P < .05). Thrombotic thrombocytopenic purpura (TTP) recurred in 5 of 85 patients; all had persistent ADAMTS13 activity < 5 IU/dL. Of 31 adverse events in 26 patients, 17 of 31 (55%) were bleeding episodes, and 5 of 31 (16%) were thrombotic events (2 unrelated to Caplacizumab); mortality was 6% (5/85), with no deaths attributed to Caplacizumab. In 4 of 5 deaths, Caplacizumab was introduced >48 hours after PEX initiation (3-21 days). This real-world evidence represents the first and largest series of TTP patients, including pediatric patients, receiving Caplacizumab outside of clinical trials. Representative of true clinical practice, the findings provide valuable information for clinicians treating TTP globally.
Cost effectiveness of Caplacizumab in acquired thrombotic thrombocytopenic purpura
Blood 2021 Feb 18;137(7):969-976.PMID:33280030DOI:10.1182/blood.2020006052.
Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by thrombotic microangiopathy leading to end-organ damage. The standard of care (SOC) treatment is therapeutic plasma exchange (TPE) alongside immunomodulation with steroids, with increasing use of rituximab ± other immunomodulatory agents. The addition of Caplacizumab, a nanobody targeting von Willebrand factor, was shown to accelerate platelet count recovery and reduce TPE treatments and hospital length of stay in TTP patients treated in 2 major randomized clinical trials. The addition of Caplacizumab to SOC also led to increased bleeding from transient reductions in von Willebrand factor and increased relapse rates. Using data from the 2 clinical trials of Caplacizumab, we performed the first-ever cost-effectiveness analysis in TTP. Over a 5-year period, the projected incremental cost-effectiveness ratio (ICER) in our Markov model was $1 482 260, significantly above the accepted 2019 US willingness-to-pay threshold of $195 300. One-way sensitivity analyses showed the utility of the well state and the cost of Caplacizumab to have the largest effects on ICER, with a reduction in Caplacizumab cost demonstrating the single greatest impact on lowering the ICER. In a probabilistic sensitivity analysis, SOC was favored over Caplacizumab in 100% of 10 000 iterations. Our data indicate that the addition of Caplacizumab to SOC in treatment of acquired TTP is not cost effective because of the high cost of the medication and its failure to improve relapse rates. The potential impact of Caplacizumab on health system cost using longer term follow-up data merits further study.
Caplacizumab: an anti-von Willebrand factor antibody for the treatment of thrombotic thrombocytopenic purpura
Am J Health Syst Pharm 2020 Jul 23;77(15):1201-1207.PMID:32588878DOI:10.1093/ajhp/zxaa151.
Purpose: The pharmacology, pharmacokinetics, efficacy, safety, dosing and administration, and place in therapy of Caplacizumab, a novel antibody fragment that inhibits von Willebrand factor, for the treatment of acquired thrombotic thrombocytopenic purpura (TTP) are summarized. Summary: Caplacizumab is a humanized anti-von Willebrand factor monoclonal antibody fragment that inhibits the interaction between ultralarge von Willebrand factor multimers and platelets. Caplacizumab is indicated for use in combination with standard-of-care modalities such as plasma exchange and immunosuppressive therapy for the treatment of adults with acquired TTP. By inhibiting von Willebrand factor, Caplacizumab offers a new approach to the management of TTP by preventing the development of potentially life-threatening microvascular thrombosis that can occur in the disease process. In a randomized, placebo-controlled phase 3 trial, patients with acquired TTP treated with Caplacizumab had more rapid platelet level normalization than placebo users; Caplacizumab use also resulted in lower rates of disease recurrence and TTP-related death. The most common adverse events associated with Caplacizumab use are bleeding-related events. In a phase 3 trial, serious bleeding-related adverse events were reported in 8 patients (11%) in the Caplacizumab group and 1 patient (1%) in the placebo group. Caplacizumab is administered as an 11-mg intravenous loading dose 15 minutes prior to plasma exchange, followed by administration of 11 mg subcutaneously daily after plasma exchange. Once-daily Caplacizumab administration can be continued for 30 days after the last plasma exchange. The medication and supplies for administration are provided as a single-use kit; patients should be trained on proper reconstitution and self-administration technique prior to the use of Caplacizumab in the ambulatory setting. Conclusion: Caplacizumab is a first-in-class von Willebrand factor inhibitor approved for the treatment of adults with acquired TTP.