FDA Says Some Preclinical Data was Manipulated for Novartis’ $2.1 Million Gen...

FDA 称,诺华(Novartis)公司210万美元的临床前数据被篡改。。。

2019-08-07 23:53:31 BioSpace

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In May, the U.S. Food and Drug Administration (FDA) approved Novartis’ gene therapy Zolgensma as a one-time treatment for spinal muscular atrophy. On Monday though, the regulatory agency revealed that data manipulation was involved in the preclinical process but suggests that the therapy remain on the market. In an announcement Monday, the FDA said on June 28, more than a month after the agency approved the gene therapy, AveXis Inc., a Novartis subsidiary, informed the FDA “about a data manipulation issue that impacts the accuracy of certain data from product testing performed in animals submitted in the biologics license application.” The FDA said it is carefully assessing the information and situation, but “remains confident” that Zolgensma should remain on the market. The FDA said its concerns are “limited to only a small portion of the product testing data that was contained in the marketing application.” That testing data was used by AveXis to support the development of its production process, the FDA said, but added that the data does not change the agency’s positive assessment of the information from the human clinical trials that were conducted as part of the development program. “The totality of the evidence demonstrating the product’s effectiveness and its safety profile continues to provide compelling evidence supporting an overall favorable benefit-risk profile. However, the integrity of the product testing data used in the development of the product’s manufacturing process is still a matter that we are continuing to evaluate and take very seriously,” the FDA announced Monday. In a statement issued Tuesday, Novartis said it stands behind the Zolgensma data. Novartis said the assays in question were used for initial product testing and are not currently used for commercial product release. “We maintain that the totality of the evidence demonstrating the product’s effectiveness and its safety profile continue to provide compelling evidence supporting an overall favorable benefit-risk profile. We remain steadfast that this important treatment remain available to pediatric patients with SMA less than two years of age,” Novartis said in its statement. “At no time during the investigation did the findings indicate issues with product safety, efficacy or quality. We remain fully capable of releasing high-quality, fully compliant Zolgensma to patients in need.” Zolgensma was approved in May as a treatment for children younger than two years old who have been diagnosed with SMA with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene. SMA is a rare, genetic neuromuscular disease caused by a defective or missing SMN1 gene. Infants with SMA lose the motor neurons responsible for muscle functions such as breathing, swallowing, speaking and walking. The disease can lead to death. Zolgensma is the first and only gene therapy approved by the FDA for the treatment of SMA, including those who are pre-symptomatic at diagnosis. At the time of its approval, Novartis Chief Executive Officer Vas Narasimhan said the company believes Zolgensma will create a “lifetime of possibilities” for children who are eligible for the treatment. He also said the therapy will be “life-changing” for the patients, as well as their families. While the FDA remains confident about the efficacy and safety of Zolgensma, which has a price tag of $2.1 million, the agency said AveXis became aware of the data manipulation issue prior to the FDA’s approval of the therapy. The FDA said it will “use its full authorities to take action” if necessary. That could include civil or criminal penalties, the agency said. The FDA said it is conducting a “thorough assessment” of the information from a recently complete inspection of AveXis’ California manufacturing facility. The assessment will allow the FDA to review its own scientific review of the Zolgensma data from the BLA and provide the agency with an opportunity to make any necessary amendments. Novartis said it does not anticipate the issues regarding the preclinical data manipulation to impact the timing of our ongoing Zolgensma regulatory filings.
今年5月,美国食品药品监督管理局(Food and Drug Administration)( FDA )批准诺华(Novartis)的基因治疗佐尔甘斯玛作为脊柱肌肉萎缩症的一次性治疗。不过,周一,监管机构透露,数据操纵涉及到临床前的过程,但暗示疗法仍在市场上。 在周一发布的一份公告中, FDA 表示,6月28日是该机构批准基因治疗一个多月后,诺华(Novartis)子公司 AveXis Inc .告知 FDA “一个数据操纵问题,影响生物制剂许可申请中提交的动物产品测试的某些数据的准确性”。FDA 表示正在仔细评估相关信息和情况,但“仍有信心”佐尔甘马应该继续留在市场上。 FDA 表示,它的担忧“仅限于市场应用程序中包含的一小部分产品测试数据。”FDA 说, AveXis 公司使用这些测试数据来支持其生产工艺的开发,但补充说,这些数据并没有改变 FDA 对作为开发计划一部分进行的人体临床试验信息的积极评估。 “证明产品有效性及其安全状况的证据总体上继续提供令人信服的证据,支持总体有利的利益风险状况。然而,在产品制造过程的开发过程中使用的产品检测数据的完整性仍然是一个我们继续评估并非常认真的问题,” FDA 周一宣布。 诺华(Novartis)在周二发布的一份声明中表示,它支持佐尔甘马的数据。诺华(Novartis)公司表示,这些检测方法用于初步产品测试,目前还没有用于商业产品发布。 “我们认为,证明产品有效性及其安全状况的所有证据继续提供令人信服的证据,支持整体有利的利益风险状况。诺华(Novartis)公司在声明中表示:“我们仍然坚定地认为,这种重要的治疗方法仍然适用于两岁以下的儿童 SMA 患者。”“在调查期间,调查结果没有显示产品安全、疗效或质量方面的问题。我们仍然完全有能力向需要的患者释放高质量、完全符合要求的佐尔甘马。” Zolgensma 于5月被批准用于治疗两岁以下的儿童,这些儿童被诊断为患有存活运动神经元1( SMN1)基因的双等位基因突变的 SMA 。SMA 是一种罕见的遗传性神经肌肉疾病,由缺陷或缺失的 SMN1基因引起。患有 SMA 的婴儿失去了负责肌肉功能的运动神经元,如呼吸、吞咽、说话和行走。这种疾病可能导致死亡。Zolgensma 是 FDA 批准的第一个也是唯一的治疗 SMA 的基因疗法,包括那些在诊断前有症状的。 在获得批准之时,诺华(Novartis)首席执行官 Vas Narasimhan 表示,该公司认为 Zolgensma 将为符合治疗条件的儿童创造“终生可能性”。他还表示,这种疗法将改变患者及其家人的生活。 虽然 FDA 对 Zolgensma 的有效性和安全性仍然充满信心, Zolgensma 的价格标签是210万美元,但该机构表示, AveXis 在 FDA 批准该疗法之前就已经意识到了数据操纵的问题。FDA 表示,必要时将“利用其全部权力机构采取行动”。该机构表示,这可能包括民事或刑事处罚。 美国食品和药物管理局表示,正在对 AveXis 加州制造工厂最近完成的一次检查中的信息进行“彻底评估”。该评估将使 FDA 能够审查自己对 BLA 中的佐尔甘马数据的科学审查,并为 FDA 提供进行任何必要修改的机会。 诺华(Novartis)公司表示,预计与临床前数据操纵有关的问题不会影响我们正在进行的 Zolgensma 监管申报的时间。

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