—Addyi被美国FDA批准第一个治疗绝经前妇女（低性欲）
2015年8月18日，美国食品和药品监管局(FDA)批准Addyi(flibanserin 中文药名 氟班色林)治疗在绝经期前妇女中获得性，普遍性活力减低性性欲障碍(HSDD)。Addyi的批准前，在男性或妇女中对于性欲障碍没有被FDA-批准的治疗。
FDA的药品评价和研究中心(CDER)主任Janet Woodcock，M.D.说：“今天的批准为被她们低性欲苦恼妇女提供一种被批准的治疗选择，” “FDA努力保护和促进妇女健康，而我们承诺支持对女性性功能障碍安全和有效治疗的发展。”
HSDD的特征是低性欲引起显著苦恼或人际交往困难和不是由于共同存在一种医疗或精神状况，相互关系内部问题，或药物或其它药物物质的作用。HSDD是获得性当它以前没有与性欲问题患者中发展。HSDD是普遍性当它发生不管性活力的类型，情况或性伴侣。
Woodcock医学博士继续说：“因为与酒精潜在地严重相互作用，将只能通过认证卫生保健专业人员和认证的药房得到用Addyi治疗，” “考虑使用Addyi治疗前患者和开处方者应充分了解伴随使用的风险。”
Addyi可能严重地引起低血压(低血压)和意识丧失(昏厥)。当患者饮酒或Addyi与某些药物服用(已知为中度或强CYP3A4抑制剂)干扰Addyi在体内分解这些风险增加和更严重。因为酒精相互作用，当服用Addyi时禁忌酒精。卫生保健专业人员必须处方Addyi之前评估患者可靠弃用酒精的可能性。
Addyi正在被批准与一个风险评估和减灾战略(REMS)，其中包括确保安全使用要素(ETASU)。FDA正在要求这个REMS因为由于Addyi和酒精间相互作用严重低血压和昏厥的增加风险。REMS要求that处方者通过纳入和完成训练用REMS计划被认证。被认证处方者必须与患者商量使用一个患者-提供者协议格式关于严重低血压和昏厥的增加风险和关于用Addyi治疗期间不饮酒的重要性。此外，药房必须通过用REMS程序纳入和完成训练被认证的。认证的药房必须只分发Addyi至患者用一个处方来自一位被认证的处方者。此外，发放前药剂师必须与患者商讨用Addyi治疗期间不饮酒。
Addyi还正在被批准有一个黑框警告强调在用Addyi治疗期间饮酒患者，在那些使用中度或强CYP3A4抑制剂，和那些有肝受损严重低血压和昏厥的风险。在这些患者中禁忌Addyi。此外，FDA正在要求公司拥有Addyi在妇女更好了解已知的Addyi和酒精间相互作用的严重风险进行三个设计良好研究。
Addyi是一个5羟色胺1A受体激动剂和一个5羟色胺2A受体拮抗剂，但是通过什么药物改进性欲和相关苦恼的机制不知道。Addyi被服用每天1次。它被在睡前时给药有助于减低不良事件风险发生由于可能性低血压，昏厥和中枢神经系统抑郁(例如嗜睡和镇静)。如治疗8周后她们没有报告性欲和关联苦恼改进她们应终止治疗。
在三项24-周随机化，双盲，安慰剂-对照试验在约2,400例绝经前妇女有获得性，普遍性HSDD中评价100 mg睡前剂量Addyi 的有效性。试验参加者平均年龄为36 岁，有一个HSDD平均时间约五年。在这些试验中，妇女计数满意性事件数，报道性欲超过以前四周(评分范围1.2 至6.0)和报道与低性欲相关苦恼(范围0至4)。用Addyi治疗平均超过安慰剂增加满意性事件数增加0.5至1附加事件每月超过安慰剂增加性欲评分0.3至0.4，和超过安慰剂减低与性欲相关苦恼0.3至0.4。开拓另外分析是否用Addyi改善对患者是否有意义，考虑见到在哪些患者报道感觉非常改善或非常全面提高中治疗影响。跨越三项试验，约10%以上Addyi-治疗患者比安慰剂-治疗患者报告在满意性事件，性欲或苦恼中有意义的改善Addyi未曾显示增强性能力[sexual performance]。
在临床试验中约3,000例一般健康绝经前妇女有获得性，普遍性HSDD曾给予100 mg睡前剂量Addyi，其中约1,700例接受治疗共至少6个月和850例接受治疗共至少一年。
伴随使用 Addyi相关最常见不良反应是眩晕，嗜睡，恶心，疲乏，失眠和口干。
FDA已认识到为女性性功能障碍发展治疗涉及挑战已有些时间了。在2014年10月27日和10月28日FDA举办一个关于女性性功能障碍的公众患者-关注药物开发会议和科学讨论会，直接从患者自己的病情和其对日常生活的影响，广泛征求观点，和探讨有关开发治疗这些疾患药物的科学挑战。FDA继续鼓励在这个领域药物开发。
消费者和卫生保健专业人员被鼓励报告来自使用Addyi不良反应至FDA的MedWatch不良事件报告程序在www.fda.gov/MedWatch或通过电话1-800-FDA-1088。
Addyi由总部在北卡罗来纳州罗利市 Sprout制药上市。

Sprout Pharmaceuticals Receives FDA Approval Of Addyi™ (flibanserin 100 mg)
Flibanserin, a Medical Treatment for Female Hypoactive Sexual Desire Disorder
Flibanserin( Addyi�)is a new drug being investigated for the prevention of HSDD in woman. HSDD, is a relatively new term developed to describe Hypoactive Sexual Desire Disorder which basically means a woman whose is otherwise healthy has a lacking libido, or a lack of sexual desire. Studies show that about 10-20% of women face this problem and some say HSDD outnumbers men with sexual problems. Flibanserin is classified as a 5-HT serotonin receptor agonist and a dopamine D4 receptor partial agonist. It is a Non-Hormonal agent that in essence increases dopamine and noradrenalin while reducing Serotonin in the brain. This in return seemingly has a positive effect on a woman's sexual craving who was otherwise lacking in this area. The benefits of it being Non-Hormonal are that it will not have the problems associated with other hormonal treatments such as a negative altered mood among other issues.
New Drugs Online Report for flibanserin
Information
Generic Name: flibanserin  
Trade Name: Addyi (US) 
Synonym: Girosa, BIMT17, BIMT17BS 
Entry Type: New molecular entity  
Development and Regulatory status
UK: None 
EU: None 
US: Approved (Licensed) 
UK launch Plans: Available only to registered users
Actual UK launch date:  
Comments
Aug 15: FDA approves Addyi for Hypoactive Sexual Desire Disorder in Premenopausal Women with a risk evaluation and mitigation strategy in place to assure safe use [21]. 
19/08/2015 14:43:32 
Jul 15: An editorial in JAMA from three of the advisory panel members notes serious concerns about a possible FDA approval. The members are troubled by the lobbying and social media campaign that resulted in an 18 to 6 FDA panel vote [20].
10/07/2015 08:39:53 
Jun 15: No information available on plans for development in countries other than the US [19].
08/06/2015 17:03:10 
Jun 15: The FDA´s Bone, Reproductive and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee vote in favour of approval of flibanserin for HSDD in premenopausal women, subject to the implementation of a risk management option beyond labelling [18].
08/06/2015 16:58:46 
Jun 15: In briefing documents posted ahead of a panel meeting on11 June, FDA staff acknowledge a consistent if modest HSDD benefit across flibanserin´s three PIII trials but noted that a litany of safety concerns, including risks of fainting and symptoms of depression, could render the drug unapprovable [17].
08/06/2015 16:31:25 
Feb 15: Sprout Pharmaceuticals resubmitted NDA to US FDA for flibanserin for treatment of Hypoactive Sexual Desire Disorder in Premenopausal Women. The resubmission comes after Sprout received a Complete Response Letter from the FDA for flibanserin in 2013. Sprout appealed the FDA´s decision, and at the request of the Agency, completed a Phase 1 pharmacokinetic study and a Phase 1 driving study. Results from these studies were included in the resubmission package [16]. 
18/02/2015 09:48:52 
Feb 14: The FDA has responded to the company´s Formal Dispute Resolution and given clear guidance on the regulatory pathway. Sprout will resubmit a marketing application in the US by Q3 2014. The FDA has requested that the company complete two additional PI drug interaction studies and a PI driving simulator study. Each study is expected to include ~ 25-50 healthy volunteers [16]. 
11/02/2014 18:02:20 
Dec 13: Sprout Pharmaceuticals announces it has received and appealed the FDA´s Complete Response Letter for flibanserin through the Formal Dispute Resolution process. The company believe they have satisfied the requirements for approval, & expects a response from the FDA on the appeal in 1Q 2014 [15].
12/12/2013 10:30:56 
Mar 13: Re-filed in the US for treatment of hypoactive sexual desire disorder in pre-menopausal women. The manufacturer expects FDA action before end 2013. The filing is based on positive results of a PIII trial involving 1,100 women. Boehringer discontinued development of the compound but then sold it to Sprout in 2011 [12,13].
27/06/2013 13:12:39 
Oct 10: Development discontinued. [11]
08/10/2010 16:46:57 
Jun 10: The FDA panel voted unanimously that an acceptable risk/benefit profile for the drug had not been demonstrated. As a consequence, the drug is unlikely to receive approval by the FDA [10].
21/06/2010 21:03:42 
Apr 10: The FDA´s reproductive health drugs advisory panel will review flibanserin on 18 June [7].
27/04/2010 22:23:42 
US launch anticipated late 2010 (6)
23/03/2010 13:20:04 
EU submission anticipated Q1 2011 (6)
23/03/2010 13:19:08 
EU submission anticipated 2012 (4)
12/08/2009 12:02:32 
Phase III (1)
19/04/2009 20:56:41 
Trial or other data
May 13: PIII trial involving 1,100 women (mean age 36.6 years) published in the Journal of Sexual Medicine. Flibanserin resulted in statistically significant improvements in the number of satisfying sexual events, as well as increase in sexual desire when compared with placebo. Flibanserin was further associated with significant reductions in distress associated with low desire, a hallmark of HSDD. The drug was well tolerated during patients´ 24 weeks of use and the most frequently reported adverse events in the flibanserin group were somnolence, dizziness and nausea. However, 9.6% of women receiving flibanserin discontinued due to adverse events versus 3.7% on placebo [12,14].
27/06/2013 13:13:50
Jun 10: In papers for the advisory panel meeting on 18th June, FDA staff state that the drug “failed to demonstrate a statistically significant improvement” in sexual desire and was linked to appendicitis, depression and loss of consciousness. Side effects led about 15% of women to stop treatment with the drug [9].
16/06/2010 20:08:15
May 10: The findings of a pre-specified pooled analysis from two PIII studies (DAISY and VIOLET) were presented at the ACOG meeting. The analysis included 1,378 pre-menopausal women with HSDD treated with either flibanserin 100mg or placebo for 24 weeks. The women assessed their overall improvement in ‘bothersome decreased sexual desire’ using the Patient´s Global Impression of Improvement (PGI-I) on a 7-point scale. By 24 weeks, 48.3% vs 30.3% of patients respectively reported feeling improved (p<0.0001). More women on flibanserin responded positively to the question - Overall, do you believe that you have experienced a meaningful benefit from the study medication? - (40.5% vs 25.2%; p<0.0001). In the PP population flibanserin 100mg significantly increased the frequency of satisfying sexual events vs placebo (increase of 2.1 events vs. 0.9 events; p<0.0001). The most commonly reported AEs were mild to moderate and emerged during the first 14 days of treatment and include somnolence, dizziness, fatigue, anxiety, dry mouth, nausea and insomnia. 15% of women on flibanserin vs 7% on placebo discontinued treatment due to AEs [8]. 
27/05/2010 09:48:06
Apr 10: An 28 week open-label PIII extension study (NCT01103362) started in Apr 10 and is expected to complete Nov 11. The purpose of the study is to generate long-term safety and efficacy data on flibanserin in premenopausal women and to establish long-term safety and tolerability of flibanserin naturally postmenopausal women with HSDD who have completed a prior clinical trial of flibanserin (Trial 511.130, 511.147, or 511.156). 1140 women will be enrolled [7].
19/04/2010 09:30:50
Feb 10: NCT01057901 is a PIII study starting Jan 10 assessing the safety and efficacy of 24-week course of flibanserin for the treatment HSDD in naturally postmenopausal women. 900 women will be treated with flibanserin 100mg or placebo once daily. The primary outcome is change from baseline in the number of satisfying sexual events based on the score on the Female Sexual Function Index (FSFI) desire domain. Estmated completion date Apr 11 [5]. 
08/02/2010 10:33:08
Jul 09: Results of the pivotal PIII studies from the BOUQUET programme are expected to be released in late 2009 [DAHLIA, ROSE, VIOLET, DAISY, ORCHID, MAGNOLIA, SUNFLOWER] (3)
12/08/2009 12:09:41
As of Apr 09, there are 3 ongoing PIII studies. NCT00491829 is a 24 week placebo controlled EU study in 900 women of flibanserin 50mg or 100mg daily. The other two studies (NCT00601367 and NCT00441558) are longer term safety studies due to complete 2H 2009 (2).
19/04/2009 21:18:21
Four PIII trials have been completed. NCT00360529 24 week placebo controlled study in North America in 886 women given 50mg and 100mg/daily flibanserin. Study completed Apr 2008. NCT00360243 was again a 24 week study in North America which completed in Apr 08; in this study 1392 women randomised to one of four arms: placebo or 25mg or 50mg twice daily, or 50mg daily of flibanserin. NCT00360555 also had 4 arms: placebo, 25mg or 50mg flibanserin twice daily or 100mg at night. This study was conducted in N America and in the EU including the UK, enrolling 1584 women, it completed Mar 08. NCT00277914 was a 12 month study in 749 women which completed in Jul 07 (2)
19/04/2009 21:12:26 
References  
Available only to registered users
 Category
BNF Category: Obstetrics, gynaecology, and urinary-tract disorders (07)
Pharmacology: Serotonin receptor agonist/ antagonist  
Epidemiology: Prevalence approx 6-13% in EU and 6-19% in USA, increasing with age.  
Indication: Female sexual dysfunction 
Additional Details: hypoactive sexual desire dysfunction in pre-menopausal women 
Method(s) of Administration  
Oral 
Company Information
Name: Not Known 
US Name: Sprout 
Further Information
Anticipated commissioning route (England) - 
High cost drug list? Awaiting Update
Tariff CCG
Implications Available only to registered users