FDA statement on data accuracy issues with recently approved gene therapy

Aug. 7, 2019

Shortly after the Food and Drug Administration approved Zolgensma, a gene therapy product for children less than two years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 gene, the Director of Center for Biologics Evaluation and Research (CBER), Dr. Peter Marks MD PhD, issued a statement related to the product’s safety and data accuracy. SMA is a leading genetic cause of infant mortality and this type is the most severe form of the disease.

On June 28, following the FDA’s approval of the product in May, the agency was informed by AveXis Inc., the product’s manufacturer, about a data manipulation issue that impacts the accuracy of certain data from product testing performed in animals submitted in the biologics license application (BLA) and reviewed by the FDA.

“As a public health agency, we believe that it is critical to facilitate the development of innovative safe and effective medical products, like the cellular and gene therapy products that have shown enormous potential to treat previously untreatable diseases,” Marks stated. “As part of the approval process for biological products, the agency reviews extensive information submitted by manufacturers, including details of how the product is made in a reproducible manner, how it has been tested in animals, and how it has been investigated in human clinical trials to demonstrate its safety and efficacy.”

The FDA said it is carefully assessing this situation and remains confident that Zolgensma should remain on the market. Out of the large amount of submitted information reviewed by the agency, FDA expressed concerns limited to only a small portion of the product testing data that was contained in the marketing application. This product testing data was used by the manufacturer to support the development of its production process.

FDA said 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. However, the integrity of the product testing data used in the development of the product’s manufacturing process is still a matter that the agency is continuing to evaluate and take very seriously.