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8:21 PM
Aug 09, 2019
 |  BioCentury  |  Regulation

Timeline of a debacle: Novartis missteps hold lessons for diligence, new modalities

How the Zolgensma debacle unfolded and signs Novartis might have missed

Editor's Note: This story has been updated to reflect the fact that Brian Kaspar, former CSO of Novartis AG's AveXis unit, has not been involved in the unit's operations since May. This article was updated on Aug 14, 2019 at 1:37 PM PDT

Aside from all the questions about who knew what when, and how they should have acted, the Zolgensma data fiasco reveals that Novartis’ due diligence team missed some warning signs. The case has the hallmarks of a cautionary tale for deals of new modalities, where bringing the right skill sets to the room and giving them long enough to sort out the issues should trump fear of missing out.

Novartis AG was rocked on Aug. 6 when FDA’s CBER Director Peter Marks issued a statement accusing the company of data manipulation related to SMA gene therapy Zolgensma onasemnogene abeparvovec-xioi. During a July 24-Aug. 2 inspection of Novartis’ San Diego manufacturing facility, FDA found multiple instances of data manipulation surrounding an in vivo mouse assay used to assess the potency of the early production lots for Zolgensma. The gene therapy will stay on the market as FDA deemed that the safety and efficacy of Zolgensma are not in question.

FDA released the inspection report, form 483, which detailed the findings and revealed that Novartis management had known about the data fudging as early as March, four months before FDA informed the public and two months before Zolgensma was approved.

Novartis received the 483 report and FDA statement at the same time it was released to the public, putting the pharma in damage control mode as it attempted to justify the lag in notifying the agency (see “Novartis Resolute That it Acted in Good Faith on Zolgensma”).

For FDA, Marks’ statement and release of the 483 report was done to ensure accuracy of the public record. The data in question were included in the BLA, details of which are publicly available on the FDA website.

However, the gush of information was uncharacteristic, as most 483 inspection reports are available to the public in FDA’s FOIA reading room, and rarely released with such fanfare.

“If AveXis had informed FDA of this issue prior to the BLA approval, I believe that the approval would have been delayed beyond the PDUFA goal date.”

Wilson Bryan, FDA

Perhaps the most comparable manufacturing issue to garner as much public attention was the 2009 contamination at Genzyme Corp.’s Allston facility, a misstep that led to the biotech’s eventual acquisition by Sanofi in 2011 (see “Allston, We Have a Problem”).

It’s unlikely that the Zolgensma data fudging will be Novartis’ undoing,...

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