The US Food and Drug Administration (FDA) has issued a statement saying the agency is investigating AveXis, a Novartis company, for knowingly submitting "manipulated data" in its application for onasemnogene abeparvovec-xioi (Zolgensma), the first gene therapy approved for spinal muscular atrophy (SMA).
AveXis "became aware of the issue of the data manipulation that created inaccuracies in their BLA [Biologics License Application] before the FDA approved the product, yet did not inform the FDA until after the product was approved," Peter Marks, MD, PhD, director of the Center for Biologics Evaluation and Research at the FDA, said in a statement released August 6.
Marks said the FDA will use its "full authorities to take action, if appropriate, which may include civil or criminal penalties."
At the same time, the FDA said Zolgensma should remain on the market for now.
SMA is caused by a mutation in the survival motor neuron 1 (SMN1) gene. The gene encodes the SMN protein critical for the maintenance and function of motor neurons. Zolgensma is an adeno-associated virus vector-based gene therapy that addresses the genetic root cause of SMA by replacing the defective or missing SMN1 gene to halt disease progression. The one-time infusion costs more than $2 million, making it the world's most expensive drug.
The FDA approved this product on May 24, as reported by Medscape Medical News.
On June 28, AveXis Inc informed the FDA about a data manipulation issue that affects the accuracy of certain data from product testing performed in animals submitted in the application reviewed by the FDA.
"It is the manufacturer's responsibility to submit complete and accurate information in marketing applications for evaluation by the FDA," said Marks. "If we become aware of a concern with data submitted to the agency as part of our review of a product application, it is in the best interest of patients, their caregivers, and the public that we disclose such information, to the extent permitted by law."
He said the FDA is "carefully assessing the situation and remains confident that Zolgensma should remain on the market."
The agency's concerns at this time are limited to a small portion of the product testing data contained in the marketing application.
"These data do not change the agency's positive assessment of the information from the human clinical trials that were conducted as part of the development program. The totality of the evidence demonstrating the product's effectiveness and its safety profile continues to provide compelling evidence supporting an overall favorable benefit-risk profile," said Marks.
"However, the integrity of the product testing data used in the development of the product's manufacturing process is still a matter that we are continuing to evaluate and take very seriously," he added.
In a statement released by Novartis one day after the FDA announcement, the company said it stands behind Zolgensma and notes "the data in question were a small portion of our overall submission and are limited to an older process no longer in use."
"At no time during the investigation did the findings indicate issues with product safety, efficacy or quality. We have and will continue to work in close cooperation with the FDA to appropriately update our submission and address any quality gaps identified," the statement reads.
"AveXis is committed to taking appropriate action to prevent future incidents across its portfolio of development programs," the company said.
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Cite this: Megan Brooks. FDA Calls Out Drug Company for 'Manipulated' Data - Medscape - Aug 09, 2019.