The Food and Drug Administration has quietly closed out an investigation of data violations tied to Novartis' gene therapy Zolgensma, indicating it will not penalize the Swiss drugmaker for submitting manipulated testing results last year.
The violations, documented in an August 2019 inspection of Novartis' AveXis unit, were at the center of a scandal which last year engulfed the pharma and marred a landmark approval for its high-profile spinal muscular atrophy treatment.
In securing the FDA's blessing for the therapy, Novartis had knowingly filed an application containing altered data from preclinical tests in mice. At the time, the FDA warned it would consider civil or criminal penalties against the company, indicating its displeasure that Novartis was aware of the issue but proceeded to ask for approval anyway.
The statement was highly unusual and a signal, former FDA officials said, to other companies in the fast-growing gene therapy field. After seven months of review, however, the FDA has decided against leveling such sanctions, a spokesperson for the agency confirmed to BioPharma Dive.
Instead, the FDA has classified its inspection review as "Voluntary Action Indicated," or VAI, which means violations were found during the inspection but didn't cross the threshold for regulatory action.
"FDA has completed its review of the information and records of the inspection, the evidence collected, and the firm's responses as well as the corrective actions to the inspectional observations, and the agency has classified the inspection as Voluntary Action Indicated," the FDA spokesperson said.
"Based on its review of the information available, FDA continues to find Zolgensma to be safe and effective for its intended use," added the spokesperson. Throughout its investigation, the FDA maintained that it found no evidence human data were changed.
FDA inspections, such as the one conducted of AveXis last August, result in what are known as Form 483s, technical documents that detail potential violations of the Food Drug and Cosmetic Act. Companies are allowed to respond, after which the FDA decides whether to proceed with a formal warning.
Novartis submitted its response to the FDA's inspection in late August last year, pledging to retrain employees and improve quality control oversight. The company placed much of the blame for the manipulation on two senior AveXis executives, Brian and Allan Kaspar, who were fired in mid August. Through his lawyer, Brian Kaspar has publicly denied any wrongdoing.
Novartis also committed to informing the FDA within five business days of any credible allegations related to data integrity questions with any pending drug application in the future.
Novartis disclosed the FDA's Form 483 classification in a presentation Monday of new clinical data for Zolgensma, briefly noting the FDA's decision.
"We are pleased with this positive outcome and reiterate our firm commitment to data integrity and transparency in our engagements with regulators," a Novartis spokesperson said in a statement.
Zolgensma was only the second gene therapy for an inherited disease to win U.S. approval, showing in clinical studies it could keep alive infants who otherwise were likely to die from spinal muscular atrophy, or SMA. The neuromuscular disease robs newborns of a protein needed for muscle development, usually leading in its most severe form to death or permanent ventilation by age two.
Some 200 infants received Zolgensma in 2019, earning Novartis $361 million last year. The one-time therapy costs $2.1 million per patient, making it the most expensive drug in the world on a per-dose basis.