In a 56-page response to the investigation from the U.S. Food and Drug Administration, Novartis said the Kaspar brothers personally manipulated or instructed others to alter some of the preclinical data that ultimately led to the approval of the $2.1 million priced SMA therapy.
Novartis continues to hold former AveXis scientists Brian and Allan Kaspar responsible for the data manipulation of Zolgensma, its gene therapy treatment for spinal muscular atrophy and stressed the brothers impeded an internal investigation.
In a 56-page response to the investigation from the U.S. Food and Drug Administration, which was made public Tuesday, Novartis said the Kaspar brothers personally manipulated or instructed others to alter some of the preclinical data that ultimately led to the approval of the $2.1 million priced SMA therapy. The company noted in its response that the manipulation primarily concerned the recorded date of death of some of the mice used in the preclinical studies. Novartis, the parent company of AveXis, insists that the data manipulation did not have any impact on the safety or effectiveness of Zolgensma. Novartis acquired AveXis last year for $8.7 billion.
The Kaspar brothers were fired from AveXis last month in the wake of the revelations regarding the data manipulation. When the terminations were announced, Novartis said the Kaspar brothers had not been involved in any operations at AveXis since early May, which was ahead of the FDA’s approval of Zolgensma.
Novartis said AveXis began an internal investigation into the allegations of data manipulation in March of this year. The company tapped outside counsel to conduct the investigation over concerns the Kaspar brothers could impede or influence the investigation, Novartis said. The Swiss pharma giant said it was informed of the internal investigation on March 28. The company noted that the investigation, which required more than 2,000 man-hours, was “drawn out” due to the “lack of cooperation and categorical denial of the allegations” by the Kaspars.
Through an attorney statement to Reuters, Brian Kaspar continues to deny any wrongdoings. Kaspar said he cooperated with the investigation, according to the attorney’s statement. Allan Kaspar did not provide comment.
In August, the FDA revealed that data manipulation was involved in the preclinical process of Zolgensma’s development. The FDA said the data manipulation was “limited to only a small portion of the product testing data that was contained in the marketing application.” But stressed that the company knew about the manipulation while the FDA was in the process of reviewing the treatment. AveXis only notified the FDA about the manipulation following the regulatory approval, the regulatory agency said at the time.
In the wake of the scandal, Novartis pledged it will be more forthcoming with any concerns over data manipulation with the FDA and other regulatory agencies. Chief Executive Officer Vas Narasimhan said the company is committed to notifying the FDA within five business days of any allegations regarding data integrity that could impact any pending applications.
Additionally, Novartis said it has helped AveXis develop and implement a company-wide compliance plan that will help it address any future data integrity concerns. The parent company also said it understands the need to “further instill a culture of quality in AveXis’s operations,” which will require a structured plan and “engagement of personnel at every level.”
AveXis has also hired senior executive compliance personnel with previous Novartis experience to facilitate the further integration of AveXis into the parent company’s organization, Novartis said. Additionally, Novartis said it will roll out its “SpeakUp” program across AveXis, which will provide employees a “clearly defined pathway for reporting concerns regarding potential misconduct or fraud.”
