Questions Pile up for Novartis as Senators Call on FDA to Take Action

Why wait three months to tell the US Food and Drug Administration (FDA) about manipulated data? Why wait two months between documenting an initial issue and opening a nonconformance report (NCR)? And how harshly will FDA act?

These questions and more are piling up for Novartis, following last week’s announcement that FDA is investigating the company for manipulating data linked to its $2.1 million gene therapy Zolgensma (onasemnogene abeparvovec-xioi). In Europe, regulators have already pulled the gene therapy’s accelerated assessment for a longer, standard assessment.

There also seem to be discrepancies between what Novartis CEO Vasant Narasimhan has said and what FDA has found. For instance, Narasimhan said in an investor call that the company launched an internal investigation into the data manipulations as soon as it learned of them in mid-March before launching a “full technical quality investigation” in May.

But the recently released FDA Form 483 said there is “no documentation” as to why an NCR was not opened until 15 May when the initial allegation is documented as having been reported on 14 March. FDA also said, “There is no documentation in this NCR that an audit of all other potentially impacted data, studies, and reports was conducted or is planned to determine if there was evidence of data mismanagement or manipulation or a justification for not conducting or planning such an audit.”

A July memorandum from Wilson Bryan, director of FDA’s Office of Tissues and Advanced Therapies, also notes that this will not be resolved in a quick manner and how the results from the Phase 3 trial do not appear to be impacted.

“A complete assessment of the impact of the data manipulation will require additional investigation, discussions both internally within CBER and with AveXis, will probably require that AveXis submit and FDA review one or more BLA supplements, and may take at least several months,” Bryan wrote. “The data manipulation seems likely to impact the interpretation of the Phase 1 clinical trial results, as well as the interpretation of the results of some, but not all, of the nonclinical studies in the original BLA. At this time, the data manipulation does not appear to impact the interpretation of the results of the animal toxicology studies or the Phase 3 clinical trial.”

Five Democratic senators (including presidential hopefuls Bernie Sanders and Elizabeth Warren) pounced on the data manipulation, saying this “scandal smacks of the pharmaceutical industry’s privilege and greed.” They also called on FDA to hold Novartis’s AveXis accountable and they questioned whether FDA has plans to re-issue a final rule on falsified data that the agency withdrew.

AveXis spokeswoman told Focus: "We have and will continue to work in close cooperation with the FDA to appropriately update our BLA submission and address any quality gaps identified." 

And Zolgensma aside, this is not the first time FDA has raised concerns about Novartis’s clinical trial operations in recent months.