2017年8月30日，美国FDA批准了公司VABOMERE注射剂（美罗培南+VABOMERE）用于成人复杂性尿路感染（cUTI）的治疗，包括由敏感肠杆菌（大肠杆菌、克雷白氏杆菌、阴沟肠杆菌）引起的肾盂肾炎。
VABOMERE由美罗培南（一种抗菌药物）和vaborbactam（可以抑制某些细菌的耐药性）组成。
VABOMERE可以应对产生了β-内酰胺酶的革兰氏阴性菌的感染，这类细菌在美国和欧洲传播广泛，尤其是产生肺炎克雷伯菌碳青霉烯酶(KPC)的细菌。产生KPC酶让肠杆菌科细菌对大量的碳青霉烯抗生素产生耐药，并已经被美国疾病控制中心列为紧急抗菌素耐药性威胁。
VABOMERE获得了FDA的优先审评资格并被授予合格传染病产品（QIDP）认定，这次获得批准，VABOMERE将拥有5年的市场独占期，这意味着该药物美国地区的专利权及排他性将会到2031年。VABOMERE由The Medicines Company的感染疾病业务部开发，是对该公司感染类疾病产品线的强力补充。
相关研究
VABOMERE获得批准的支持数据来自TANGO-1研究，这是一项多中心、随机、双盲、双模拟临床3期试验，研究了VABOMERE相比哌拉西林-他唑巴坦治疗复杂性尿路感染（包括急性肾盂肾炎）的有效性、安全性及耐受情况。试验共入组了550名成人患者，被随机按照1:1分别接受每8小时内3个小时的VABOMERE (美罗培南 2g-vaborbactam 2g)静脉注射治疗或每8小时内30分钟的哌拉西林 4g–他唑巴坦 500mg的治疗，两组患者均持续治疗10天以上。
该项研究在微生物学上意向治疗群体(m-mITT)中进行了主要的评估，主要疗效终点被定义为“临床结果的整体成功”（治愈或改善）以及微生物学的根除结果（基线细菌病原体降低到< 104 CFU/ml）。整体试验成功结果方面，VABOMERE组有183/186 名患者 (98.4%)达到该标准，哌拉西林-他唑巴坦组达到该标准的人数为165/175 名患者 (94.3%)，两组有4.1%的差异（95% CI: 0.3% - 8.8%）。VABOMERE组最常见不良反应有头痛、注射部位不适和腹泻。
TANGO临床研究项目的数据（包括多中心、随机开标的、与“最佳疗法“相对照的TANGO-2试验，患者为已知或疑似碳青霉烯耐药的肠杆菌感染患者）将会于10月4-8日在圣地亚哥召开的IDWeek 2017上公布。就在上个月，依照独立数据和安全监测委员会的建议，TANGO-2的患者招募暂停，原因为已得到数据的风险-获益分析(http://www.chemdrug.com/sell/76/)结果无法支持其他待入组患者随机分配到“最佳疗法”对照组。
VABOMERE被预计可以在2017年第四季度上市。VABOMERE获得FDA的批准，可以让VABOMERE之前的所有权公司Rempex Pharmaceuticals获得4000万美元的里程碑款项
VABOMERE™ (meropenem and vaborbactam) for injection
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use VABOMERE safely and effectively. See full prescribing information for VABOMERE.
VABOMERE™ (meropenem and vaborbactam) for injection, for intravenous use
Initial U.S. Approval: 2017
INDICATIONS AND USAGE
VABOMERE (meropenem and vaborbactam) is a combination of meropenem, a penem antibacterial, and vaborbactam, a beta‑lactamase inhibitor, indicated for the treatment of patients 18 years and older with complicated urinary tract infections (cUTI) including pyelonephritis caused by designated susceptible bacteria. (1.1)
To reduce the development of drug‑resistant bacteria and maintain the effectiveness of VABOMERE and other antibacterial drugs, VABOMERE should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. (1.2)
DOSAGE AND ADMINISTRATION
Administer VABOMERE 4 grams (meropenem 2 grams and vaborbactam 2 grams) every 8 hours by intravenous infusion over 3 hours for up to 14 days, in patients 18 years of age and older with an estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m2. (2.1)
Dosage adjustment is recommended in patients with renal impairment who have an eGFR less than 50 mL/min/ 1.73m2. (2.2)
a As calculated using the Modification of Diet in Renal Disease (MDRD) formula; b All doses of VABOMERE are administered intravenously over 3 hours; c Doses adjusted for renal impairment should be administered after a hemodialysis session; d The total duration of treatment is for up to 14 days.
See Full Prescribing Information for instructions for constituting supplied dry powder and subsequent required dilution. (2.3)
See Full Prescribing Information for drug compatibilities. (2.4)
DOSAGE FORMS AND STRENGTHS
VABOMERE 2 grams (meropenem and vaborbactam) for injection, is supplied as a sterile powder for constitution in single‑dose vials containing meropenem 1 gram (equivalent to 1.14 grams of meropenem trihydrate) and vaborbactam1 gram. (3)
CONTRAINDICATIONS
Known hypersensitivity to the components of VABOMERE (meropenem and vaborbactam) or anaphylactic reactions to beta‑lactams. (4)
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions were reported with the use of VABOMERE. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterial drugs. Discontinue infusion if signs of acute hypersensitivity occur. (5.1)
Seizures and other adverse Central Nervous System experiences have been reported during treatment with meropenem, a component of VABOMERE. (5.2)
Clostridium difficile-associated diarrhea has been reported with nearly all systemic antibacterial agents, including VABOMERE. eva luate patients if diarrhea occurs. (5.3)
Co-administration of meropenem with valproic acid or divalproex sodium reduces the serum concentration of valproic acid potentially increasing the risk of breakthrough seizures. (5.4, 7.1)
ADVERSE REACTIONS
The most frequently reported adverse reactions occurring in ≥3% of patients treated with VABOMERE were headache, phlebitis/infusion site reactions, and diarrhea. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact The Medicines Company at 1-888-977-6326 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. |
