FDA Says Some Preclinical Data was Manipulated for Novartis’ Gene Therapy Drug Zolgensma

In May, the U.S. Food and Drug Administration (FDA) approved Novartis’ gene therapy Zolgensma as a one-time treatment for spinal muscular atrophy. On Monday though, the regulatory agency revealed that data manipulation was involved in the preclinical process but suggests that the therapy remain on the market.

In an announcement Monday, the FDA said on June 28, more than a month after the agency approved the gene therapy, AveXis Inc., a Novartis subsidiary, informed the FDA “about a data manipulation issue that impacts the accuracy of certain data from product testing performed in animals submitted in the biologics license application.” The FDA said it is carefully assessing the information and situation, but “remains confident” that Zolgensma should remain on the market.

The FDA said its concerns are “limited to only a small portion of the product testing data that was contained in the marketing application.” That testing data was used by AveXis to support the development of its production process, the FDA said, but added that the data does 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,” the FDA announced Monday.

In a statement issued Tuesday, Novartis said it stands behind the Zolgensma data. Novartis said the assays in question were used for initial product testing and are not currently used for commercial product release.

“We maintain that the totality of the evidence demonstrating the product’s effectiveness and its safety profile continue to provide compelling evidence supporting an overall favorable benefit-risk profile. We remain steadfast that this important treatment remain available to pediatric patients with SMA less than two years of age,” Novartis said in its statement. “At no time during the investigation did the findings indicate issues with product safety, efficacy or quality. We remain fully capable of releasing high-quality, fully compliant Zolgensma to patients in need.”

Zolgensma was approved in May as a treatment for children younger than two years old who have been diagnosed with SMA with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene. SMA is a rare, genetic neuromuscular disease caused by a defective or missing SMN1 gene. Infants with SMA lose the motor neurons responsible for muscle functions such as breathing, swallowing, speaking and walking. The disease can lead to death. Zolgensma is the first and only gene therapy approved by the FDA for the treatment of SMA, including those who are pre-symptomatic at diagnosis.

At the time of its approval, Novartis Chief Executive Officer Vas Narasimhan said the company believes Zolgensma will create a “lifetime of possibilities” for children who are eligible for the treatment. He also said the therapy will be “life-changing” for the patients, as well as their families.

While the FDA remains confident about the efficacy and safety of Zolgensma, which has a price tag of $2.1 million, the agency said AveXis became aware of the data manipulation issue prior to the FDA’s approval of the therapy. The FDA said it will “use its full authorities to take action” if necessary. That could include civil or criminal penalties, the agency said.

The FDA said it is conducting a “thorough assessment” of the information from a recently complete inspection of AveXis’ California manufacturing facility. The assessment will allow the FDA to review its own scientific review of the Zolgensma data from the BLA and provide the agency with an opportunity to make any necessary amendments.

Novartis said it does not anticipate the issues regarding the preclinical data manipulation to impact the timing of our ongoing Zolgensma regulatory filings.