A U.S. Food and Drug Administration advisory panel will weigh the evidence that ulipristal acetate can be used as an emergency contraceptive if taken within 120 hours of unprotected intercourse or known or suspected contraceptive failure.

Ulipristal acetate is a new chemical entity with a different mechanism of action from levonorgestrel, the currently approved emergency contraceptive (EC). It is a selective progesterone receptor modulator, and would be the first in this class to receive approval for EC in the United States. If approved, it would be marketed in the United States by HRA Pharma under the trade name Ella. It was approved by the European Medicines Agency in May 2009.

The drug would be able to be used later after unprotected intercourse than levonorgestrel which is indicated for emergency contraception up to 72 hours after unprotected intercourse. Two phase III clinical trials “provide support for the safety and efficacy of ulipristal acetate for EC from zero to 120 hours after [unprotected intercourse],” FDA officials wrote in a briefing document released before the June 17 meeting of the Reproductive Health Drugs Advisory Committee.

The FDA and HRA Pharma seem to be in broad agreement that the two Phase III studies for EC show ulipristal acetate to be safe and effective.

Overall, FDA said, ulipristal acetate reduced the observed pregnancy rate in both trials to a level “statistically lower than the expected pregnancy rate in the absence of EC and lower than the clinical relevance threshold of 4%.”

There were no deaths or unexpected adverse outcomes in any of the clinical trials, according to the briefing documents, which noted “the most common adverse reactions were nausea, headache, dysmenorrhea, abdominal pain, fatigue and dizziness.”

The possible effect of ulipristal acetate on fetal development if a woman taking it does become pregnant remains “unknown,” Dr. Carole Ben-Maimon, who served as president of the research division of Barr Laboratories during the time Plan B was in development, said in an interview. This is as a result of the smaller amount of safety data available on the new drug as compared to the older one, although a relatively large number of spontaneous abortions occurred in the patients who got ulipristal acetate in the clinical trials, she said.

However, “the FDA has always been comfortable with emergency contraception,” Dr. Ben-Maimon, who will be speaking at the advisory panel meeting, said.

In addition to the basic safety and efficacy questions, the FDA will also ask the advisory committee to review the pharmacovigilance plan HRA Pharma has put in place in Europe and determine whether it is sufficient; whether the labeling should include specific advice for certain subpopulations, such as women with a body mass index of more than 30 kg/m², in whom the drug seems to be less effective; and whether additional steps are needed to prevent off-label use.

美国食品药品管理局(FDA)顾问专家组将评估以下证据，即醋酸ulipristal可在无保护性交或已知(或怀疑)避孕失败120 h内作为紧急避孕剂使用的效果。

 

醋酸ulipristal是一种新化学实体，其作用机制与左炔诺孕酮不同，目前已获批用于紧急避孕(EC)。醋酸ulipristal是一种选择性孕酮受体调节剂，并将是这类药品中第一个获美国批准用于EC的药物。如果获批，则其将由HRA Pharma公司在美国市场销售，商品名为Ella。该药已在2009年5月得到欧洲药品局批准。

 

目前左炔诺孕酮标明适用于无保护性交72 h内紧急避孕，而醋酸ulipristal可在这之后更长时间内使用。FDA官员在一份于生殖健康药品顾问委员会6月17日会议之前发布的简报文件中写道：两项III期临床试验“提供了在(无保护性交后)0~120 h内使用醋酸ulipristal进行紧急避孕安全和有效的证据”。

 

FDA和HRA Pharma公司似乎达成了广泛共识，即这两项有关EC的III期临床研究显示，醋酸ulipristal安全且有效。

 

FDA称，总的来说，在这两项试验中，醋酸ulipristal将观察到的妊娠率减少至 “统计学上低于预期的缺乏EC的妊娠率，并低于4%的临床相关阈值。”

 

根据简报文件，在两项临床试验中，未发生任何死亡或意外的不良结果。“最常见的不良反应是恶心、头痛、痛经、腹痛、乏力和头晕。”

 

在B计划开发阶段担任巴尔实验室研究部总裁的Carole Ben-Maimon博士在接受采访时说，如果妇女服用该药时已经怀孕，则醋酸ulipristal对胎儿发育的可能影响“尚不清楚”。这是因为现有关于该新药的安全性数据较少(与较老的药品相比)，尽管在临床试验中，服用醋酸ulipristal的患者中发生自然流产的比例相对较高，她说。

 

然而，Ben-Maimon博士说： “对于紧急避孕，FDA一直信心十足。”她将在顾问委员会会议上发言。

 

除了基本的安全和有效性问题，FDA还将要求顾问委员会审查HRA Pharma已在欧洲实施的药物警戒计划，并确定其是否足够；标签是否应包括针对某些亚组人群的具体意见，例如体重指数>30kg/m²的妇女，其效能可能较低；是否需要额外的措施来防止标签外使用。

 

醋酸ulipristal最初由美国国立卫生研究院的国立儿童健康与人类发展研究所开发。HRA Pharma在2000年得到生产许可。这家法国公司已得到为日内瓦PregLem公司开发治疗子宫肌瘤的药物的许可，这种药物正在进行III期临床试验。

 

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