U.K. drug experts called for GlaxoSmithKline's diabetes therapy Avandia (rosiglitazone) to be withdrawn two months ago because of side effects, a British Medical Journal article published online Sept. 6 has revealed.

 

However, the lack of transparency in the European Union regulatory process prevented public access to the views of the Commission on Human Medicines, the U.K.'s top medicines advisory body, the article claims.

 

In a statement, the U.K. regulator, the Medicines and Healthcare Regulatory products Agency, which takes advice from the CHM, confirmed the accuracy of the claims but indicated that it could not take action straight away because its hands were tied by European regulations.

 

"The CHM advised in July 2010 that the risks of rosiglitazone outweigh its benefits and that it no longer has a place on the U.K. market," the MHRA said. But this advice had to be reviewed by other European regulators.

 

"Rosiglitazone is licensed on a Europe-wide basis by the European Medicines Agency (EMA), not directly by the MHRA ... it has therefore been necessary to review the balance of risks and benefits of this medicine throughout Europe, in response to emerging evidence," the MHRA explained.

 

The MHRA said that it would use the CHM advice "to robustly put forward the U.K.'s position in Europe."

 

On July 26, the MHRA sent out a "dear doctor" letter to all U.K. healthcare professionals, which advised that they should closely observe the current contraindications, warnings and precautions and monitoring requirements for rosiglitazone, and should consider alternative treatments where appropriate. But there is no mention of the CHM's views.

 

The revelations have caused a furor in the U.K, which is only expected to increase after the airing of a BBC TV "Panoroma" programme entitled "A Risk Worth Taking?" on the evening of Sept. 6 that discusses the controversy surrounding Avandia.

 

EMA Moves Avandia Discussion Forward

 

And in a surprise move announced on Sept. 3, the EMA revealed that it was holding an extraordinary meeting of the Committee for Medicinal Products for Human Use (CHMP) on Wednesday, Sept. 8, to discuss the risks and benefits of Avandia. Previously, the CHMP said that it would discuss Avandia at its scheduled meeting on September 20-23 ('The Pink Sheet' DAILY, July 27, 2010).

 

"Because of the complexity of the data being assessed, the committee is holding this additional meeting outside of its usual monthly schedule," EMA said. However, a decision is not expected until its scheduled meeting at the end of September, the agency added.

 

The CHMP advises the European Commission on the licensing or withdrawal of drugs, and its advice is usually followed by the commission, and applied across Europe. However, all CHMP meetings are held in private, and no minutes are publicly released - the outcomes of discussions are disseminated via statements on its website.

 

GSK: Nothing To Hide

 

In a further twist, GSK has put an audio tape recording on its website of a meeting between Avandia critic Steven Nissen from the Cleveland Clinic and four GSK medical and clinical experts, held in May 2007. The recording was subpoenaed from Nissen by GSK, which alleges that Nissen made the tape covertly.

 

The BMJ article contrasts the non-transparent approach of European regulators with the more open attitude of those in the U.S. It notes that the U.S. FDA's advisory panel meeting on Avandia in July was held in front of a packed audience, including the world's media ('The Pink Sheet' DAILY, July 14, 2010), and the results of the FDA's deliberations on the matter were expected shortly.

 

GSK said it understood the Panorama programme would feature the recording, and Panorama pre-publicity materials suggested that it was a "secret tape the drug company would rather you didn't hear." The company has therefore subpoenaed the tape and put it on its website, "so that all interested parties can hear all the comments made at this meeting in their full context."

《英国医学杂志》(BMJ)9月6日在线发表的一篇文章披露， 英国药品专家曾在2个月前就呼呼，鉴于葛兰素史克(GSK)公司生产的降糖药文迪雅(Avandia，罗格列酮)的副作用，应尽快令其撤市。

 

该文章称，欧盟监管程序的不透明使英国最权威的医疗产品咨询机构——人类药品委员会(CHM)的专家意见并没有公诸于众。

 

作为英国的监管机构，英国药品和健康产品监管局(MHRA)通常会征求CHM的意见。MHRA在一份声明中证实了这篇文章的真实性，但指出由于受到欧盟条款的限制，他们不能直接采取行动。

 

MHRA表示：“CHM于2010年7月向我们建议，鉴于罗格列酮的风险已经超过了其能产生的效益，因此不应继续在英国市场上销售。”但这项建议必须经过欧盟监管机构的审核。

 

MHRA解释道：“罗格列酮是经欧盟药品管理局(EMA)批准可以在全欧洲市场上销售，并不是直接由MHRA批准的……因此如今出现了这些新的证据，也必需是在整个欧洲范围内对该药的风险和效益进行评估。”

 

MHRA称将基于CHM的建议“向欧盟监管机构强烈表达英国的立场。”

 

7月26日，MHRA向全英所有的医务人员发送了一份警示信，建议其密切关注罗格列酮的现有禁忌证、警告与注意事项以及监测要求，并在恰当的时候考虑改用其他治疗。但信中并没有提到CHM的观点。

 

此事一经披露，便在英国掀起了一场轩然大波，9月6日晚BBC TV “Panoroma”栏目一期名为“值得这样冒险吗？”的节目对围绕文迪雅事件的各方争论进行了讨论，估计节目播出以后这个事件还会再次升级。

 

EMA就文迪雅事件展开讨论

 

9月3日，EMA出乎意料地宣布，将于周三也就是9月8日召开人用医疗产品委员会(CHMP)特别会议，讨论文迪雅的利弊问题。之前，CHMP曾表示原计划是在9月20~23日开会讨论文迪雅的问题('The Pink Sheet' DAILY, July 27, 2010)。

 

EMA表示：“鉴于所评估数据的复杂性，该委员会是在其每月的例行会议安排之外召开这次特别会议。”但EMA补充道，预计最终决议还是要等到其原定日期，也就是9月底才会公布。

 

按惯例，CHMP会向欧盟委员会建议批准或撤销某种药物，而且欧盟委员会通常都会采纳CHMP的建议，并在全欧洲范围内实施。但所有的CHMP会议都是私下召开的，从不对外公布具体的会议内容，只是通过其官网上的声明公布讨论结果。

 

GSK：没什么可隐瞒的

 

令事情更加曲折的是，GSK在其官网上公布了一份录音带，这份录音带记录了2007年5月文迪雅的反对者美国克利夫兰诊所的Steven Nissen医生与4名GSK医学和临床专家之间展开的一次讨论。GSK声称Nissen是在背地里录下了这段录音，因此要求Nissen交出这份录音带。

 

GSK表示他们早就知道Panorama栏目组会在这份录音带上下功夫，节目播出前的宣传语称这是“一份药品生产商希望你永远都不要听到的秘密录音带。”因此，GSK要求拿到这份录音带并把它放到了网上，“这样一来，对此事感兴趣的所有人都可以完整地听到这次讨论会的所有内容。”

 

这篇BMJ文章将欧盟监管机构的不透明程序与美国所持的更加公开的态度进行了对比。文章指出，美国FDA针对文迪雅事件于今年7月召开的顾问专家小组会议是当着满屋子的听众召开的，其中包括来自全球各地的媒体('The Pink Sheet' DAILY, July 14, 2010)，而且FDA对此事的审议结果很快就会公布。