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. 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. 

It is the manufacturer’s responsibility to submit complete and accurate information in marketing applications for evaluation by the FDA. 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.

On May 24, the FDA approved Zolgensma, a gene therapy product intended to treat children less than two years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 gene — the most severe form of SMA. SMA is a leading genetic cause of infant mortality. Subsequently, on June 28, following the FDA’s approval of the product, 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. 

The FDA 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, our concerns at this time are 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 for the product. 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 we are continuing to evaluate and take very seriously.

Ensuring truthful, complete and accurate data in product applications is a critical component of industry’s responsibility as they work to demonstrate the safety, purity, and potency of biological products. The submission of such truthful, complete and accurate data is also critical for the FDA to be able to protect the public health, and the law requires it. We are carefully assessing the issue of the manipulation of the product testing data used in the production process and are conducting a thorough assessment of the information from a recently completed inspection.  In part, this will allow us to determine the implications for the FDA’s scientific review of the information in the BLA and will allow us to amend our publicly posted BLA reviews, as appropriate.

We are also aware that AveXis became aware of the issue of the data manipulation that created inaccuracies in their BLA before the FDA approved the product, yet did not inform the FDA until after the product was approved. The agency will use its full authorities to take action, if appropriate, which may include civil or criminal penalties.

We recognize that parents of, and health care professionals for, children with SMA may have questions or concerns about this information. Parents and health care professionals may contact the FDA at (800) 835-4709 or AveXis for more information. The FDA will continue to provide updates related to this statement as we learn more.

As with all biological products, health care professionals and patients (or for Zolgensma, their caregivers) should be aware of both the product’s benefits and risks. The most common side effects of Zolgensma are elevated liver enzymes and vomiting. Zolgensma has a boxed warning that acute serious liver injury can occur. Health care professionals and caregivers should refer to the product package insert for additional risk information.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

###

---

---

Related Information