Novartis Blames Zolgensma Data Manipulation on Two Fired Senior Executives

Regulatory NewsRegulatory News | 24 September 2019 |  By 

In its response to a US Food and Drug Administration (FDA) Form 483, Novartis said in a document released Tuesday that two senior executives at its subsidiary AveXis “could not offer a credible explanation for revisions to and inconsistencies in the data” and were later fired from their positions in August.

The firings follow the revelation last month that AveXis manipulated some of the nonclinical data included in the biologic license application for its billion-dollar spinal muscular atrophy gene therapy Zolgensma (onasemnogene abeparvovec-xioi). However, FDA confirmed that the data manipulation does not impact the approval or benefit-risk determination for Zolgensma.

The 483 response also follows a pledge made by Novartis earlier this month that the company will inform FDA within five business days of any credible allegation related to data integrity.

But how FDA will react to Novartis’ response to the Form 483 remains unknown.

Acting FDA Commissioner Ned Sharpless did not mention Novartis by name, but clearly singled the company out in his remarks before the Research!America 2019 National Health Forum earlier this month. Sharpless said: “So it should not be surprising to me now at FDA that if people will lie to get their paper published or get their grant funded, then people will also lie to get a billion dollar medical product approved.”

As far as why Novartis waited to report the data manipulation to FDA, which raised eyebrows when first announced, the 483 response says the timing “was based in part on the fact that the investigation into the data integrity manipulation issues was highly complex, and involved review of a significant amount of data, including manual comparisons of raw data on the individual mouse data sheets and cage cards, and identification of technical experts to assess the impact.”

Novartis also said that it engaged with an independent third-party cGMP consultant to assess AveXis’s data integrity controls and oversight and to investigate the extent of the data integrity deficiencies noted in the 483 and the data manipulation issues previously reported by the company to FDA.

AveXis also said it’s undergoing a company-wide Compliance Action Plan, and said it is confident that the plan, alongside the actions described in AveXis’s specific responses to the 483 observations, “will fully address any data integrity and broader GxP compliance concerns raised in the 483.”

Form 483 Response


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