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Motavizumab

(Synonyms: MEDI-524) 目录号 : GC68286

Motavizumab (MEDI-524) 是一种 anti-human RSV (呼吸道合胞病毒) 单克隆抗体。Motavizumab 可用于高危婴儿的呼吸道合胞病毒感染的研究。

Motavizumab Chemical Structure

Cas No.:677010-34-3

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5mg
¥11,520.00
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产品描述

Motavizumab (MEDI-524) is an anti-human RSV (respiratory syncytial virus) monoclonal antibody. Motavizumab can be used in respiratory syncytial virus infection in high-risk infants research[1].

Motavizumab shows activity after F protein initiates interaction with the cell membrane and before virus transcription[2].
Motavizumab inhibits F protein-mediated cell-to-cell fusion[2].

Motavizumab (intraperitoneal injection; 1.25 mg in 0.1 ml of PBS/per mouse; once) treatment shows reductions on RSV replication and concentrations of cytokine and chemokines in RSV-infected mice[1].

Animal Model: Seven-week-old female, pathogen-free BALB/c mice intranasally inoculated with 106.5 PFU RSV-A2[1]
Dosage: 1.25 mg in 0.1 ml of PBS/per mouse
Administration: Intraperitoneal injection; 1.25 mg in 0.1 ml of PBS/per mouse; once
Result: Resulted in significant reductions of RSV loads compared with untreated controls on days 1 and 5.
Showed lower BAL concentrations of IL-1α, IL-12p70, TNF-α and IFN-γ and serum IL-10 and KC compared with RSV-infected untreated mice.

[1]. MejÍas A, et al. Motavizumab, a neutralizing anti-Respiratory Syncytial Virus (Rsv) monoclonal antibody significantly modifies the local and systemic cytokine responses induced by Rsv in the mouse model. Virol J. 2007 Oct 25;4:109.
[2]. Huang K, et al. Respiratory syncytial virus-neutralizing monoclonal antibodies motavizumab and palivizumab inhibit fusion. J Virol. 2010 Aug;84(16):8132-40.

Chemical Properties

Cas No. 677010-34-3 SDF Download SDF
别名 MEDI-524
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Research Update

A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults

Antimicrob Agents Chemother 2013 Dec;57(12):6147-53.PMID:24080653DOI:10.1128/AAC.01285-13.

The study objective was to evaluate the pharmacokinetics (PK), antidrug antibody (ADA), and safety of motavizumab-YTE (Motavizumab with amino acid substitutions M252Y/S254T/T256E [YTE]), an Fc-modified anti-respiratory syncytial virus (RSV) monoclonal antibody. Healthy adults (n = 31) were randomized to receive a single intravenous (i.v.) dose of motavizumab-YTE or Motavizumab (0.3, 3, 15, or 30 mg/kg) and followed for 240 days. Clearance of motavizumab-YTE was significantly lower (71% to 86%) and the half-life (t1/2) was 2- to 4-fold longer than with Motavizumab. However, similar peak concentrations and volume-of-distribution values, indicative of similar distribution properties, were seen at all dose levels. The sustained serum concentrations of motavizumab-YTE were fully functional, as shown by RSV neutralizing activity that persisted for 240 days with motavizumab-YTE versus 90 days postdose for Motavizumab. Safety and incidence of ADA were comparable between groups. In this first study of an Fc-modified monoclonal antibody in humans, motavizumab-YTE was well tolerated and exhibited an extended half-life of up to 100 days. (This study has been registered at ClinicalTrials.gov under registration no. NCT00578682.).

Motavizumab

MAbs 2009 Sep-Oct;1(5):439-42.PMID:20065632DOI:10.4161/mabs.1.5.9496.

Motavizumab (MEDI-524, Numax) is a second generation monoclonal antibody (mAb) derived from palivizumab (Synagis) using affinity maturation techniques. Motavizumab is currently undergoing US Food and Drug Administration review as a treatment for respiratory syncytial virus (RSV) prophylaxis. It has been evaluated in large-scale clinical studies, and has demonstrated efficacy in reducing the disease burden of RSV in high-risk infant populations.

Motavizumab for the prevention of respiratory syncytial virus infection in infants

Expert Opin Biol Ther 2009 Oct;9(10):1335-45.PMID:19764889DOI:10.1517/14712590903287499.

Background: Respiratory syncytial virus (RSV) is the most important respiratory viral pathogen of infancy. The only unequivocally effective pharmacological compound for the management of RSV infection is palivizumab, a monoclonal antibody against the fusion protein of RSV. Recently, Motavizumab, a similar but more potent monoclonal antibody, has been developed and tested against palivizumab. Objective: In this review, we summarize data comparing the safety and efficacy of the two monoclonal antibodies in prevention of RSV infection. Other therapeutic options also are discussed. Methods: We reviewed all published articles listing Motavizumab or palivizumab in the title or keywords. Results/conclusion: In a large comparative clinical trial for which peer review is pending, Motavizumab proved noninferior to palivizumab for prevention of RSV-related hospital admission in infants with underlying conditions placing them at high risk for hospitalization after RSV infection. In this trial, Motavizumab in comparison to palivizumab significantly reduced the severity of illness among those infants hospitalized with RSV infection, as well as the number of outpatient lower respiratory infections caused by RSV. Safety profiles of each of the two compounds were excellent. Based on these data, Motavizumab should eventually replace palivizumab in the prevention of RSV infection.

Motavizumab for prophylaxis of respiratory syncytial virus in high-risk children: a noninferiority trial

Pediatrics 2010 Jan;125(1):e35-51.PMID:20008423DOI:10.1542/peds.2008-1036.

Objective: Palivizumab reduces respiratory syncytial virus (RSV) hospitalization in children at high risk by approximately 50% compared with placebo. We compared the efficacy and safety of Motavizumab, an investigational monoclonal antibody with enhanced anti-RSV activity in preclinical studies, with palivizumab. Methods: This randomized, double-blind, multinational, phase 3, noninferiority trial assessed safety and RSV hospitalization in 6635 preterm infants aged Motavizumab monthly. Secondary end points included outpatient medically attended lower respiratory tract infections (MALRIs), RSV-specific LRIs, otitis media, antibiotic use, development of antimotavizumab antibodies, and Motavizumab serum concentrations. Results: Motavizumab recipients had a 26% relative reduction in RSV hospitalization compared with palivizumab recipients, achieving noninferiority. Motavizumab was superior to palivizumab for reduction of RSV-specific outpatient MALRIs (50% relative reduction). Overall, adverse events (AEs) were not significantly different between groups. Cutaneous events were reported in 2 percentage points more Motavizumab recipients (7.2% vs 5.1%); most were mild, but 0.3% resulted in dosing discontinuation. Antidrug antibodies (ADA) were detected in 1.8% of Motavizumab recipients. Patients with anti-drug antibody reported 6 RSV events and 17 cutaneous events. Conclusions: Children receiving prophylaxis with Motavizumab or palivizumab had low rates of RSV hospitalization; Motavizumab recipients experienced 50% fewer RSV MALRIs than palivizumab recipients. AEs were similar in both groups, although cutaneous AEs were higher for Motavizumab recipients. Motavizumab may offer an improved alternative in prophylaxis for serious RSV disease in infants and children at high risk.

Motavizumab treatment of infants hospitalized with respiratory syncytial virus infection does not decrease viral load or severity of illness

Pediatr Infect Dis J 2014 Jul;33(7):703-9.PMID:24356256DOI:10.1097/INF.0000000000000240.

Background: This study was conducted to determine whether treatment with Motavizumab, an anti-respiratory syncytial virus (RSV) monoclonal antibody, would decrease viral load and improve clinical outcomes in previously healthy term infants hospitalized with RSV lower respiratory tract infection. Methods: Infants hospitalized with lower respiratory tract infection and a positive RSV test performed locally were randomized to receive 1 intravenous dose of Motavizumab (30 or 100 mg/kg) or placebo. Nasal wash samples were tested by real-time reverse transcriptase polymerase chain reaction at a central laboratory to determine viral load. Clinical data were collected during RSV hospitalization and at 12-month follow up. Results: Of 118 infants, 112 were confirmed RSV positive by real-time reverse transcriptase polymerase chain reaction. In each study group, median (range) RSV load (log10 copies/mL) decreased at a similar rate from baseline to study day 7 [Motavizumab 30 mg/kg: 8.35 (2.5-9.5) to 5.03 (2.5-6.8); Motavizumab 100 mg/kg: 8.22 (5.5-9.7) to 4.25 (2.5-8.0); placebo: 8.02 (6.7-9.8) to 5.17 (2.5-7.3)]. Median (range) duration of hospitalization was 3.05 (0.8-16.0), 2.99 (1.0-25.0) and 2.88 (0.8-11.7) days for the Motavizumab 30 mg/kg, Motavizumab 100 mg/kg and placebo groups, respectively. Six (8%) Motavizumab and 0 placebo recipients were admitted to the intensive care unit and 4 required mechanical ventilation. The incidence of wheezing episodes during the 12-month follow up was comparable for all 3 groups. Conclusions: Motavizumab had no appreciable effect on RSV viral load measured in the upper respiratory tract of children hospitalized for RSV lower respiratory tract infection. No differences were observed for duration of hospitalization, severity of illness measures or wheezing episodes during 12-month follow up in children treated with Motavizumab or placebo.