Novartis, under fire for manipulating data for its gene therapy Zolgensma and for delays in alerting the FDA, has come up with a late fix that could for once put it ahead of its pharma peers, transparency-wise.
The Swiss drugmaker has "voluntarily and proactively" pledged to the FDA that it will inform the agency within five business days about "any credible allegation of a data integrity issue of any filing in the Novartis Group that reaches our quality organization," Novartis CEO Vas Narasimhan said at an investor conference in London Monday.
Novartis' AveXis unit included the promise in a response to the FDA Form 483 issued after the company finally disclosed the data problem to the agency, Novartis told FiercePharma.
That agency citation raised questions about the Novartis unit's handling of the data problems, including who knew what—and when. Besides answering specific knocks in that Form 483, the carefully worded pledge also might sway the FDA as it weighs penalties against the company for the tainted data, which was included in its application for Zolgensma approval.
In early August, the FDA announced that AveXis had informed it in late June about problems with certain animal testing data included in that application. Novartis later said its internal investigation had confirmed in early May that the data were falsified.
Zolgensma was approved May 24, some days after the in-house confirmation but a full month before AveXis actually turned itself in to the FDA. Critics argue the company might have deliberately withheld the information to ensure the FDA ruling came on time.
“We did not delay any of the [investigation] due to the timing of the Zolgenmsa BLA,” Narasimhan said during an investor call shortly after the news broke. Instead, after the early May finding, the company launched a detailed search as “a full technical quality investigation” to see whether it needs to update the regulatory filings, he said at the time.
During an on-site inspection at AveXis’ lab in California, though, inspectors found the company didn’t open a formal internal probe, known as a nonconformance report, until May 15, two months after an AveXis scientist told management about the falsified data. That delay was cited in the Form 483.
Novartis, in response to FiercePharma a few days ago, said it was doing the first phase of the investigation during that period. “This was a highly complex investigation given the high variability of the assay and the need to obtain a data trail to conduct the assessment,” it said.
Detailed explanations of this two-phase investigation and answers to why it waited so long to make disclosures to the FDA have been included in its response to the Form 483 it filed August 23, Novartis said.
As for Narasimhan, the CEO first said “we did the best we could” as the data crisis developed, but later admitted to Swiss newspaper Schweiz am Wochenende that he saw where Novartis could have done a better job.
And now, Narasimhan says Novartis should have considered the fact that Zolgesma would be a new gene therapy approved by the agency. That unique situation “is something that should be taken into account with regard to timing of FDA notifications of data integrity investigations,” he told investors at Monday’s event. Still he insisted the company had done everything “fully in line with regulations, [...] past industry precedents and with our own standard operating procedures.”
In addition to the FDA, Novartis “will take a similar approach in other jurisdictions, absent a specific local regulation to the contrary” in disclosing any data problems within five business days, he said.
Still, Novartis has yet to navigate through the Zolgensma scandal at hand, as the FDA has said it is evaluating possible civil or criminal penalties even though it believes the drug should stay on the market.