Novartis ousted scientists before reporting drug data manipulation


2019-08-15 14:01:00 Financial Times


Novartis placed senior scientists on administrative leave more than a month before it told the US regulator that it suspected data manipulation in early studies on gene therapy submitted as part of an approval for the world’s most expensive drug. The pharmaceutical company said on Wednesday that two brothers who were scientists at AveXis, the unit that Novartis bought for $8.7bn last year, had not been involved in any operations at the company since early May and have since left. A person close to the company said that a few other scientists had left with the Kantar brothers and investigations were continuing. The news of the timing of the administrative leave comes after analysts and politicians have raised questions about whether Novartis should have informed the FDA before it approved the drug on May 28. The company waited another month, until it had completed an internal investigation and the drug was approved, to tell the FDA. Brian Kaspar, chief scientific officer, and Allan Kaspar, senior vice-president of research and development, were placed on leave before Novartis informed the Food and Drug Administration that it suspected there had been a problem with some of the data used in animal studies during the development of Zolgensma, a gene therapy treatment for spinal muscular atrophy that is now on the market for $2.1m. The Kaspar brothers did not respond to request for comment on Wednesday. The FDA said it is now investigating data manipulation at the Novartis unit, warning that the company could face civil or criminal penalties. But the regulator has stressed its confidence in the treatment remaining on the market. Trials in humans demonstrated that the drug was safe and effective enough for approval, the FDA said. The US Senate finance committee is investigating the incident. Senator Chuck Grassley has written to Vas Narasimhan, Novartis chief executive, asking questions about the timeline of events and who is being held responsible. The Kaspar brothers will be replaced by Page Bouchard, who will take on both the roles of senior vice-president of research and chief scientific officer. He has been with Novartis for ten years and was most recently the global head of pre-clinical safety for the Novartis institutes for BioMedical Research. Novartis said it began its investigation in mid-March 2019 after it received allegations of data manipulation with a subset of its data in mice. From mid-March to mid-May, it conducted an independent investigation with support of external counsel to determine if the claims were true. In early May, Novartis began a second part of its investigation by its internal quality organisation to determine if they needed to update their regulatory filings. Novartis is waiting for approval for Zolgensma in Japan and the EU and has informed regulators in both regions of the data manipulation. Approval in the EU is taking longer than expected and was temporarily paused in June because of questions that Novartis said were unrelated to the data integrity issue. Novartis said it believed that the accelerated review status was dropped because of the complexity of gene therapy products, as it had with other drugs. Novartis ADRs fell 2 per cent to $89.24 in late afternoon trading in New York, slightly less than the wider market. Zurich-traded shares lost 1.2 per cent.
诺华( Novartis )在一个多月前向美国监管机构表示,在提交的基因治疗早期研究报告中,该公司怀疑存在数据操纵行为,这是全球最贵药物获得批准的一部分。 这家制药公司周三表示,诺华(Novartis)去年以87亿美元收购的艾维斯公司( AveXis )的两位科学家兄弟自5月初以来从未参与过该公司的任何业务,自那以后也没有参与。 一位与该公司关系密切的人士表示,其他一些科学家已经离开了 Kantar 兄弟公司,调查仍在继续。 在此之前,分析师和政界人士对诺华(Novartis)是否应该在5月28日批准该药之前通知 FDA 提出了质疑。该公司又等了一个月,直到完成了一项内部调查并获得批准,才告诉 FDA 。 首席科学官 Brian Kaspar 和研发高级副总裁 Allan Kaspar 在诺华(Novartis)通知美国食品和药物管理局( Food and Drug Administration )其怀疑 Zolgensma 研发过程中使用的一些动物研究数据存在问题之前被停职。目前市场上售价210万美元的脊肌萎缩症基因治疗。 卡斯帕兄弟周三没有回应记者的置评请求。 FDA 表示,目前正在调查诺华(Novartis)公司的数据操纵行为,警告该公司可能面临民事或刑事处罚。但监管机构强调,它对市场上依然存在的待遇充满信心。美国食品和药物管理局说,人体试验表明,这种药物足够安全和有效,可以获得批准。 美国参议院财政委员会正在调查此事。参议员查克•格拉斯利( Chuck Grassley )已致函诺华(Novartis)首席执行官瓦丝•纳拉西汉( Vas Narasimhan ),询问有关事件时间表和谁应对此事负责的问题。 卡斯帕兄弟将由佩奇·布查德取代,布查德将同时担任研究高级副总裁和首席科学官。他在诺华工作了十年,最近是诺华(Novartis)生物医学研究所临床前安全全球主管。 诺华(Novartis)表示,该公司在2019年3月中旬开始调查,此前该公司收到了一项指控,称其数据中的一小部分是老鼠数据。 3月中旬至5月中旬,它在外部律师的支持下进行了独立调查,以确定这些指控是否属实。今年5月初,诺华( Novartis )开始了其内部质量组织调查的第二部分,以确定是否需要更新其监管申报文件。 诺华(Novartis)正在等待日本和欧盟批准佐尔甘斯曼,并已向两个地区的监管机构通报了数据操纵情况。欧盟的审批比预期时间要长,由于诺华(Novartis)表示与数据完整性问题无关的问题,6月暂时暂停审批。诺华(Novartis)公司表示,它认为,由于基因治疗产品的复杂性,加速审评的地位下降了,就像其他药物一样。 诺华( Novartis )美国存托凭证( ADR )在纽约午后交易中下跌2%,至89.24美元,略低于大盘。苏黎世上市股票下跌1.2%。