Zolgensma data: ‘Heavy-handiness’ of FDA a warning to industry, not just Novartis

The US FDA may have made an example of Novartis in the way it handled the revelation of Zolgensma data manipulation, says the Alliance for Regenerative Medicine.

A month after the US Food and Drug Administration (FDA) approved the one-time gene therapy Zolgensma (onasemnogene abeparvovec), marketing authorization holder Novartis alerted the agency to a data manipulation issue that impacted the accuracy of certain data from product testing performed in animals submitted in the biologics license application (BLA).

In its response, the FDA inspected a quality control laboratory in San Diego, California, run by Novartis subsidiary AveXis, and on August 2 issued a Form 483.

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Days later, Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research (CBER) issued a statement about the incident asserting: “The agency will use its full authorities to take action, if appropriate, which may include civil or criminal penalties.”


Janet Lambert, CEO of industry advocacy group the Alliance for Regenerative Medicine (ARM), said the FDA has always been supportive of cell and gene therapy sponsors and its statement may be more directed to the wider industry rather than just to Novartis/AveXis.

Speaking at Biotech Week Boston this month, she said that while she did not know the specific details of the Zolgensma case she was “a bit surprised at the heavy-handiness of the FDA’s announcement.”

In response to a question from Bioprocess Insider, Lambert said the FDA’s statement wasn’t subtle, but rather “a very firm announcement,” and “when I read that announcement it seems to me they weren’t just talking to one sponsor, they were trying to talk to sponsors at large.”

The FDA, she continued, “has been such a good partner to this sector and so willing to work with sponsors who have in many cases been working on rare diseases and have a pretty limited data,” but “it’s possible that they really wanted to say ‘hey look, we are a good partner to you but we’re expecting a certain behavior from sponsors too,’” with these actions.

“That said, I think sponsors at large are trying to get this right and do right by their submissions and so I think in that sense it won’t necessarily change anyone’s behavior.”

Lambert’s views seem to be supported by comments made by acting FDA Commissioner Ned Sharpless at 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,” Zachary Brennan from RAPS reported recently.

483 response and ‘terminated’ executives

The FDA, meanwhile, has published AveXis’ initial response to the 483, which blames two senior executives on the data manipulation. Both executives have lost their jobs, the reply states:

“As FDA is aware, the July/August 2019 Inspection followed AveXis’s June 28, 2019 self-reporting to the agency of data manipulation issues involving a mouse potency assay – known as the in vivo relative potency assay (IVRPA) – used as a product release test during the early clinical phase of Zolgensma (onasemnogene abeparvovec-xioi),” the Novartis subsidiary wrote.

“Specifically, it was alleged that two AveXis senior executives altered or instructed others to alter a small amount of raw data used to run the IVRPA. Such conduct is unacceptable, and the two AveXis senior executives have been terminated.”