FDA says some data supporting approval of Novartis' gene therapy Zolgensma may have been manipulated

The FDA on Tuesday stated that it was recently notified by Novartis' AveXis unit that some data submitted as part of its filing seeking approval of the gene therapy Zolgensma (onasemnogene abeparvovac-xioi) may have been manipulated. Nevertheless, the FDA believes the $2.1-million therapy, which was authorised in May for the treatment of certain patients with spinal muscular atrophy, should remain on the market given that its concerns "are limited to only a small portion of the product testing data that was contained in the marketing application." 

However, the FDA noted that AveXis did not inform the agency until June 28 of the data manipulation issue that "created inaccuracies" in the filing, despite being aware of the problem prior to Zolgensma's approval. Acting FDA Commissioner Ned Sharpless stressed that the agency depends "on truthful scientific data to make regulatory decisions, and we take the issue of data integrity very seriously." He indicated that "in this case, the agency will use its full authorities to take action, if appropriate, which may include civil or criminal penalties."

According to the FDA, the product testing data in question were used by Novartis to support the development of its production process for Zolgensma. "These data do not change [our] positive assessment of the information from the human clinical trials that were conducted as part of the development programme," the agency said, adding that "the totality of the evidence demonstrating the product's effectiveness and its safety profile continues to provide compelling evidence supporting an overall favourable benefit-risk profile." 

The FDA indicated that it is carefully assessing the issue and also evaluating findings from a recently completed inspection. "In part, this will allow us to determine the implications for the FDA's scientific review of the information in the [filing] and...amend our publicly posted [filing] reviews, as appropriate," the agency said.

Novartis, whose shares fell as much as 3.6% on the news, gained rights to Zolgensma, also known as AVXS-101, as part of its $8.7-billion purchase of AveXis in 2018. The Swiss drugmaker explained that the issue relates to "a specific animal testing procedure," adding that "the assays in question...are not currently used for commercial product release." Novartis conducted a probe into the matter, noting "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."

For related analysis, see ViewPoints: Novartis' Zolgensma sets the new status quo. See also ViewPoints: Payers hopeful that Zolgensma may spark new thinking in gene therapy cost models.

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