Novartis faced tough questions from investment bank analysts Wednesday morning in the aftermath of revelations that some of the preclinical data for its recently approved gene therapy were manipulated and that the company did not disclose the findings to the agency until after the therapy was approved.
The Food and Drug Administration had revealed Tuesday that some data from a potency assay used to test Zolgensma (onasemnogene abeparvovec-xioi) in mice had been manipulated. Furthermore, AveXis – the developer of Zolgensma that the Swiss drugmaker acquired last April for $8.7 billion – had learned about the issue in the middle of March, but did not inform the agency until late June – more than a month after Zolgensma’s May 24 approval for spinal muscular atrophy in infants.
On the conference call, Novartis CEO Vas Narasimhan defended the company and its product.
“First and foremost, we are fully confident in the safety, quality and efficacy of Zolgensma,” Narasimhan said in his opening remarks on the call. “The FDA supports the continued marketing and use of Zolgensma for patients with spinal muscular atrophy at less than 2 years of age. And we maintain that the totality of evidence demonstrating the product’s effectiveness and its safety profile continue to provide compelling evidence supporting an overall favorable benefit-risk profile and – importantly in my mind – an important benefit for these babies.”
The company’s shares had fallen by as much as 4 percent on the Nasdaq following the Tuesday revelation, and the FDA’s statement suggested the possibility of civil and criminal legal action. On Wednesday, Novartis’ shares were down nearly 3 percent on the SIX Swiss Exchange in Zurich, but up very slightly on the New York Stock Exchange.
Narasimhan said on the call that AveXis had discontinued use of the in vivo potency assay in question around June of last year and has since relied on the current assay. He also emphasized that a particular issue raised in the FDA’s statement – that Novartis had delayed informing the agency until after approval, as informing it prior to that would have delayed the FDA’s decision – was not due to the timing of its approval application. Rather, he said, the company sought to conduct a thorough investigation before going to the agency.
“We made the decision to progress our quality investigation prior to informing the FDA and other regulatory authorities so that we could provide the best information and technical analysis, which we did promptly on completion, on June 28,” he said.
Nevertheless, analysts grilled the CEO and other executives on the call, seeking reassurance that the reason for not disclosing the information more promptly was solely for the sake of data collection and that the manipulation was not part of a larger systemic issue at AveXis.
“This was an isolated incident of certain individuals,” Narasimhan said, adding that the scientists in question would be fired from the company. He also said it occurred prior to Novartis’ acquisition of the company.
AveXis President David Lennon, who was also on the call, noted that AveXis has changed almost its entire management team since the Novartis acquisition and hired nearly 1,000 people, and the manipulation issue was “historic in nature.”
The data manipulation issue is also the reason why the European Medicines Agency dropped Zolgensma from accelerated assessment, Lennon said, stating that the volume of questions the company had received and the time needed to address them meant Zolgensma would lose accelerated assessment. However, it is still on track for approval in the fourth quarter, while other indications for Zolgensma in the U.S. likewise remain on track.
The European regulator had previously said it would remove the therapy from accelerated assessment – meaning it would be reviewed in 210 days instead of the expedited 150 days – but did not explain why. Novartis had told the Regulatory Affairs Professionals Society’s online publication Regulatory Focus that the longer review would give the EMA time to review “the robust amount of data we are providing to answer their questions.”
Photo: Novartis
