The agency said the gene therapy should remain on the market while it assesses the situation and does not impact their evaluation of data from the human clinical trials.
Peter Marks, MD, PhD
The FDA has released a statement announcing that data from early testing of onasemonogene abeparvovec (Zolgensma, AveXis), the first and only gene therapy approved for spinal muscular atrophy in pediatric patients 2 years of age and younger with mutations in the SMN1 gene, was manipulated. The agency said that the therapy should remain on the market while it assesses the situation.
AveXis Inc., a subsidiary of Novartis, informed the agency of the data manipulation on June 28, just over a month following the therapy's momentous approval. From the large amount of data submitted and reviewed by the agency, at this time, the manipulation concerns are confined to only a small portion of the product testing data that was performed in animals and submitted in the biologics license application. The product testing data was used by AveXis to support the development of its production.
The manipulated information does not change the FDA’s positive assessment of data from the human clinical trials. The agency will continue to evaluate the integrity of the product testing data used in the development of the therapy’s manufacturing process. According to the agency, the evidence demonstrating Zolgensma’s efficacy and safety profile provides convincing evidence supporting an overall favorable risk-benefit profile.
“We are also aware that AveXis became aware of the issue of the data manipulation that created inaccuracies in their 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 FDA’s Center for Biologics Evaluation and Research, said in a statement.1 “The agency will use its full authorities to take action, if appropriate, which may include civil or criminal penalties.”
The European Medicines Agency Committee for Medicinal Products for Human Use recently announced its decision to remove the therapy from its accelerated assessment program and is now under standard approval.2
"At no time during the investigation did the findings indicate issues with product safety, efficacy or quality," Novartis said in a statement.3 "We remain fully capable of releasing high-quality, fully compliant Zolgensma to patients in need. We have and will continue to work in close cooperation with the FDA to appropriately update our submission and address any quality gaps identified. We are committed to ensuring the highest levels of transparency and integrity with health agencies, as well as with the patients and providers we serve. We do not expect this to impact the timing of our ongoing Zolgensma regulatory filings and development programs. AveXis is committed to taking appropriate action to prevent future incidents across its portfolio of development programs."
In a tweet, acting FDA Commissioner Ned Sharpless, MD, said that the agency relies “on truthful scientific data to make regulatory decisions, and we take the issue of data integrity very seriously."
We rely on truthful scientific data to make regulatory decisions, and we take the issue of data integrity very seriously. In this case, the agency will use its full authorities to take action, if appropriate, which may include civil or criminal penalties. https://t.co/lGu4cAw6B5
— Dr. Ned Sharpless (@FDACommissioner) August 6, 2019
A single dose of Zolgensma is currently priced at $2.125 million.
1. Statement on data accuracy issues with recently approved gene therapy. FDA website. https://www.fda.gov/news-events/press-announcements/statement-data-accuracy-issues-recently-approved-gene-therapy. Published Aug. 6, 2019. Accessed Aug. 6, 2019.
2. Novartis’ Zolgensma Joins Growing List of Medicines to Lose Accelerated Assessment Status in EU. https://www.raps.org/news-and-articles/news-articles/2019/7/novartis-zolgensma-joins-growing-list-of-medicine. Accessed Aug. 6, 2019.
3. Novartis stands behind Zolgensma® (onasemnogene abeparvovecxioi) for the treatment of children less than 2 years of age with spinal muscular atrophy [news release]. Basel Switzerland: Novartis; Aug. 6, 2019. https://ml-eu.globenewswire.com/Resource/Download/1e173c4c-a7b7-4b7f-86f7-a9956631843c. Accessed Aug. 6, 2019.