奈瑞莫单抗(Nerelimomab) - 药物靶点：TNF_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

Nerelimomab (USAN/INN)、Norasept、BAY 1351

+ [2]

靶点

TNF

作用机制

TNF抑制剂(肿瘤坏死因子抑制剂)、免疫抑制剂

治疗领域

感染其他疾病

在研适应症-

非在研适应症

脓毒性休克

原研机构

Celltech Oy

在研机构-

非在研机构

Celltech Group Plc

Chiron Corp.

Bayer AG

+ [1]

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

登录后查看时间轴

关联

100 项与奈瑞莫单抗相关的临床结果

登录后查看更多信息

100 项与奈瑞莫单抗相关的转化医学

登录后查看更多信息

100 项与奈瑞莫单抗相关的专利（医药）

登录后查看更多信息

3

项与奈瑞莫单抗相关的文献（医药）

2003-01-01·Drugs in R&D4区 · 医学

CDP 571

4区 · 医学

ReviewOA

作者: &NA;

CDP 571 [anti-TNF monoclonal antibody, BAY 103356, BAY W 3356, Humicade] is a recombinant humanised antibody directed against tumour necrosis factor (TNF). CDP 571 has an advantage over the mouse/human chimera anti-TNF-alpha antibody, nerelimomab, in that it is suitable for multiple dosing as it is not so immunogenic. Celltech constructed CDP 571 by grafting the section of mouse antibody that recognises TNF onto a human IgG4 antibody. In the third quarter of 1999, Celltech merged with Chiroscience to form Celltech Chiroscience. In January 2000, Medeva was merged into Celltech Chiroscience, which was renamed as Celltech Group. The research division of Celltech Group is now called Celltech R&D (formerly Celltech Chiroscience Discovery) and the manufacturing and marketing division is called Celltech Pharmaceuticals (formerly Celltech Medeva Pharma). Celltech has completed two phase III trials, involving around 670 patients with moderate-to-severe Crohn's disease; however, both these trials failed to meet their primary endpoints. Biogen and Celltech group will review the scope of their collaboration following additional analysis of the phase III data and discussions with regulatory authorities. The Celltech Group intends to devote significant resources towards enhancing the capability of Celltech Pharmaceuticals to market CDP 571 and other new drugs (such as CDP 860 and CDP 870) as specialised hospital products. Phase II trials were underway in the United Kingdom for use of the drug in the treatment of type 2 diabetes mellitus. However, these trials have also been discontinued. Celltech Group is no longer developing CDP 571 for septic shock, based on negative results with the related compound nerelimomab. The compound was in phase III trials for septic shock in France, Belgium, the United Kingdom, Germany and the US. Celltech also plans to investigate the use of CDP 571 in psoriasis via a collaboration with Biogen (USA). In January 2002, AFX (Agence France-Presse and the Financial Times Group) reported that analysts at Morgan Stanley have forecast Humicade trade mark to reach sales of 250 million US dollars in 2008--at that time, the market value for anti-TNF products to treat rheumatoid arthritis and Crohn's disease will exceed 4 billion US dollars, according to Morgan Stanley.

2000-06-19·Intensive care medicine1区 · 医学

Hypothermia and cytokines in septic shock

1区 · 医学

Article

作者: Zaloga Gp ; Marik Pe

BACKGROUND:

Hypothermic patients with sepsis have been reported to have a higher mortality than febrile septic patients. The failure to mount a febrile response in sepsis is poorly understood. Since the proinflammatory cytokines play a crucial role in the genesis of fever, we postulated that hypothermic patients with sepsis would have lower circulating levels of these cytokines than febrile patients.

METHODS:

Patients with septic shock who were enrolled into the placebo limb of the North American study of the safety and efficacy of murine monoclonal antibody to tumor necrosis factor for the treatment of septic shock (NORASEPT II) were analyzed. Body temperature, interleukin-6, tumor necrosis factor alpha, soluble tumor necrosis factor receptor-55, and soluble tumor necrosis factor receptor-75 concentrations were measured at enrollment. The study population was divided into a hypothermic (temperature < 35.6 degrees C) and a febrile group (temperature > or = 38.3 degrees C) according to the core temperature at enrollment (normothermia was an exclusion criteria). Clinical, demographic, and cytokine data were extracted, allowing for comparisons between these two groups of patients. In addition, the correlation between the core body temperature and cytokine levels at enrollment was determined.

RESULTS:

A complete data set was available for 930 patients; 195 patients (21%) were hypothermic at enrollment. The 28-day survival of these patients was significantly lower than that of the febrile patients (34% vs. 59%, p < 0.001). Hypothermia (and enrollment temperature) were independent predictors of mortality. The hypothermic patients had a higher incidence of organ dysfunction at enrollment than the febrile patients. There was no significant difference in the cytokine profile between the two groups of patients. In addition, there was no correlation between the core body temperature at enrollment and the circulating levels of cytokines measured.

CONCLUSION:

Hypothermic patients with septic shock have a significantly higher mortality with a higher incidence of organ dysfunction than febrile septic shock patients. The hypothermia in these patients cannot be explained by lower levels of circulating proinflammatory cytokines.

1996-09-01·Critical care medicine1区 · 医学

INTERSEPT

1区 · 医学

Article

作者: Carlet, J ; Cohen, J

OBJECTIVE:

To determine the safety and efficacy of BAY x 1351, a murine monoclonal antibody to recombinant human tumor necrosis factor (TNF)-alpha, in patients with sepsis.

DESIGN:

An international, multicenter, prospective, placebo-controlled trial in patients with sepsis, stratified into shock/nonshock groups.

SETTING:

Forty acute clinical care facilities in 14 countries.

PATIENTS:

Of the 564 patients enrolled in the study, 553 patients received study drug or placebo.

INTERVENTIONS:

Patients received 15 mg/kg or 3 mg/kg of BAY x 1351, or placebo, as a single intravenous infusion.

MEASUREMENTS AND MAIN RESULTS:

The patients were well matched for severity of illness and for risk factors known to influence the outcome of sepsis. There was no difference in 28-day mortality rates between groups (placebo group 66 [39.5%] of 167;3 mg/kg group 57 [31.5%] of 181; 15 mg/kg group 87 [42.4%] of 205). Approximately 9 months after this study had begun, an interim safety examination of NORASEPT, a North American Sepsis Trial using the same monoclonal antibody, indicated that there was no benefit to patients in the nonshock group and further enrollment of these nonshock septic patients into INTERSEPT was stopped. The analysis therefore focused on the 420 patients in shock. The primary efficacy variable was the 28-day, all-cause mortality rate: placebo group 57 (42.9%) of 133; 3-mg/kg group 51 (36.7%) of 139; and 15-mg/kg group 66 (44.6%) of 148 (not significant). Two secondary efficacy variables were identified prospectively: shock reversal and frequency of organ failures. Life-table analysis showed that in patients who survived 28 days, there was a more rapid reversal of shock in both treatment groups compared with placebo (15-mg/kg group vs. placebo group log-rank statistic p = .007, 3-mg/kg group vs. placebo group p = .01). Similarly, in patients surviving 28 days, there was a significant delay in the time to the onset of first organ failure (log rank 15 mg/kg vs. placebo p = .03, 3 mg/kg vs. placebo p = .07), and more patients in the placebo group developed at least one organ failure: 15-mg/kg group 33 (40.2%) of 82; 3-mg/kg group 39 (44.3%) of 88; and placebo group 45 (59.2%) of 76 (15 mg/kg vs. placebo p = .03, 3 mg/kg vs. placebo p = .06). No significant adverse events were associated with the monoclonal antibody treatment.

CONCLUSIONS:

INTERSEPT provides additional clinical data implicating TNF-alpha as an integral mediator of septic shock. The study suggested a possible role for anti-TNF antibody as adjunctive therapy, but this possibility requires confirmation by another clinical trial.

100 项与奈瑞莫单抗相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D05146	奈瑞莫单抗	-	-

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
脓毒性休克	临床3期	美国	-	-
脓毒性休克	临床3期	法国	Celltech Group Plc	-
脓毒性休克	临床3期	德国	-	-
脓毒性休克	临床3期	英国	Celltech Group Plc	-
脓毒性休克	临床3期	-	Bayer AG	-
脓毒性休克	临床3期	-	Chiron Corp.	-
脓毒性休克	临床3期	-	Celltech Oy	-