Novartis AG did not inform the U.S. Food and Drug Administration about inaccurate data on its gene therapy Zolgensma while the agency was reviewing the drug for approval, even though the Swiss pharmaceutical giant had known as early as mid-March.
But Novartis CEO Vas Narasimhan said on Aug. 7, "We tried to do the right thing in this instance."
Zolgensma, a $2.1 million gene therapy developed by AveXis Inc. for rare infant disorder spinal muscular atrophy, was approved by the FDA on May 24. Novartis acquired AveXis in April 2018.
As the drug was being reviewed, Novartis had been conducting an independent investigation with external counsel to validate the data manipulation claims. In early May, the investigation confirmed that a "small number" of scientists at AveXis had manipulated a test in mice during preclinical work to achieve certain outcomes.
Novartis CEO Vas Narasimhan.
Narasimhan said the company had confirmed during this period that the data inaccuracies stemming from the older test, which was discontinued in July 2018, would not affect the ultimate drug's efficacy, safety and product quality.
Novartis "proactively" informed the FDA of its findings June 28, Narasimhan said during the Aug. 7 call. The FDA conducted onsite inspections in early August, and the information was made public Aug. 6, with the regulatory agency stating that "civil or criminal penalties" may be appropriate.
Nevertheless, the FDA agreed that the data integrity issues should not impact Zolgensma's benefits as shown during clinical trials.
"We did exactly what we do in every case, which is inform the agency once we actually understand the information we have in hand," said Rob Kowalski, Novartis' head of regulatory affairs.
Kowalski said Novartis would have informed the FDA before conducting the independent investigation only if patients were in immediate danger, "which was not the case here."
"We want to emphasize we did not delay any of the above due to the timing of Zolgensma's [biologics license application]," Narasimhan said.
However, HSBC Global Research analyst Steve McGarry believes that Zolgensma's approval would likely have been delayed if the FDA had been informed prior to its approval decision.
"For a company that has stated ethics and conduct are a top priority ... the company has some explaining to do," McGarry wrote in an Aug. 7 note.
Narasimhan pointed out that as of July 1 and 2, Novartis has informed European and Japanese regulatory authorities, who had been reviewing Zolgensma's application for approval.
As the company has since received a large volume of questions after the revelation of data inaccuracies in early animal models, Zolgensma has been moved out of the accelerated assessment process originally granted by the EU's regulatory authorities, AveXis president David Lennon confirmed.
Narasimhan said the data issues should not impact the company's development programs, including plans to approve Zolgensma for an additional intrathecal administration method.
But McGarry warned that, regardless of whether or not the FDA pursues civil or criminal penalties, Novartis "can expect a higher degree of regulatory scrutiny for any new drug filing."
A 'historic,' not systemic issue
Novartis is in the process of "exiting" the individual scientists involved with the data manipulation, with plans to get in place new leaders in AveXis, Narasimhan said.
He added that the development of the manipulated mouse assay happened prior to Novartis' acquisition of AveXis, and Lennon emphasized that the issue is "historic in nature."
"Is this a systemic issue at AveXis, I don't believe so — it was an isolated incident," Narasimhan said.
In addition to reshuffling the AveXis team, Novartis is retesting products that had been used in any early trials to ensure they conform to the current testing being used for Zolgensma's commercial release, Lennon said.
The company is also initiating outreach to its key opinion leaders, medical experts and advocacy groups to answer questions regarding Zolgensma.
"We are committed to rebuild trust with society, deeply from me personally all the way through the leadership team as a broader organization," Narasimhan said. "It's a long road and sometimes it's bumpy."