Novartis delayed notifying about gene therapy data manipulation until after approval, FDA says

The US Food and Drug Administration has strongly criticised the Novartis subsidiary AveXis for failing to immediately pass on its discovery that data had been manipulated in the early stages of testing Zolgensma (onasemnogene abeparvovec-xioi), a new gene therapy for spinal muscular atrophy, which at $2.1m (£1.7m; €1.9m) a dose is the most expensive drug in the world.

“AveXis became aware of the issue of the data manipulation that created inaccuracies in their biologics licence application before the FDA approved the product, yet did not inform the FDA until after the product was approved,” said Peter Marks, director of the FDA’s biologics division, in a statement.1

“The agency will use its full authorities to take action, if appropriate, which may include civil or criminal penalties.”

AveXis learnt of the manipulation this March, the FDA said. Zolgensma was approved on 24 May. Only on 28 June did the company notify the FDA of the flawed data. Had the agency known earlier, approval would have been delayed while it investigated.

The data in question did not affect the overall risk-benefit profile of the therapy, the FDA said, and the agency has no plans to reverse its approval. The manipulations “are limited to only a small portion of the product testing data that was contained in the marketing application,” the statement said.

The manipulated results were in animal testing, not human trials, and the tests affected were aimed at supporting the case for a particular manufacturing process, rather than efficacy or safety, said the FDA.

Nevertheless, said the FDA’s acting commissioner, Ned Sharpless, “we rely on truthful scientific data to make regulatory decisions, and we take the issue of data integrity very seriously.”

In a statement Novartis said that when it learnt of the manipulation “an investigation was immediately initiated to rapidly understand any implications and address the situation. Once we had interim conclusions from our investigations, we shared our findings with the FDA.”

Novartis’s share price fell 4% in the hours after the FDA’s 6 August statement. The next day, several company executives, including chief executive Vas Narasimhan, held a conference call with reporters and investment analysts to provide a fuller account.

An AveXis scientist reported the fraud in mid-March, Narasimhan said. By early May a preliminary investigation had confirmed the scientist’s allegations of data manipulation, he said, but Novartis then launched a “full technical investigation,” which was still ongoing when the drug was approved.

“We tried to do all of the right things,” said Narasimhan, adding that his job was to rebuild public trust after recent lawsuits alleging bribery and kickbacks to doctors who prescribed the company’s products. “We understand the agency has a different perspective which we can respect.”

The management team at AveXis has been largely replaced since Novartis acquired it last year, he said.

“We are now in the process of exiting the small number of AveXis scientists involved in these data inaccuracies,” said Narasimhan. “We do not believe this issue extends beyond these individuals.”

The Novartis executives also said that Zolgensma’s approval in Europe was no longer being fast tracked, for unrelated reasons.