Why the FDA Dropped the Hammer on Novartis Data Manipulation Scandal

In early August, the U.S. Food and Drug Administration (FDA) announced that the data involved in the preclinical approval process of Novartis’ gene therapy Zolgensma for spinal muscular atrophy (SMA) was manipulated. The therapy, which was developed by AveXis, a Novartis subsidiary, was approved by the agency in May.

Some have wondered why the agency has hit back at Novartis so hard when the data in question didn’t have any effect on the eventual outcomes of the product’s effectiveness and safety.

In the original announcement, the FDA said AveXis informed the agency “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 data was used by the company to support the development of its production process, and the data does not seem to change the agency’s positive assessment of the information from the human clinical trials.

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research,wrote the original FDA memo that started the crisis and told STAT that any time data is mishandled and leads to a patient being harmed, it sets the entire field back and undermines the public trust in the agency and the pharmaceutical industry. Although as far as is known, nobody has been harmed anywhere along the way in the Novartis Zolgensma development and approval process, Marks cited Jesse Gelsinger, who died in September 1999 during a gene therapy clinical trial.

That clinical trial was run by the University of Pennsylvania and was a gene therapy for ornithine transcarbalmylase deficiency, which includes an inability to metabolize ammonia. Gelsinger had a massive immune response to the gene therapy that led to multiple organ failure and brain death.

“We just so happened to be lucky in this case that when we look at everything, at the end of the day, there’s no concern about this particular product,” Marks told STAT. “But we don’t want anyone to think that it isn’t important to do the right thing and to make sure that the information that we get is correct.”

The data manipulation in the Novartis’ Zolgensma case didn’t undermine the benefits of the therapy. The issues revolved around efforts AveXis researchers took to evaluate the potency of the viruses used in Zolgensma to carry the new genetic material. It was used to compare earlier and later versions of the therapeutic used in clinical trials.

Part of what has made the story so big is simply timing—because of the presidential election cycle, drug pricing is a hot-button issue. The U.S. Senate has weighed in on the issue. Specifically, U.S. Senate Finance Committee Chairman Chuck Grassley (R-IA) has requested details about the data manipulation. Five senators, including presidential candidates Elizabeth Warren (D-MA) and Bernie Sanders (I-VT), wrote a letter to the FDA urging it to take forceful action.

Reportedly the FDA has referred the matter to its Office of Criminal Investigations to launch a preliminary inquiry. Submitting false data to the FDA as part of a New Drug Application (NDA) could be a crime if the investigation finds the actions were intentional.

So far Novartis has ousted five of the scientists involved in the scandal and appointed a new chief scientific officer for AveXis. AveXis has also parted ways with its scientific founder and chief scientific officer. Brian Kaspar, chief scientific officer, and Allan Kaspar, the company’s head of research and development, are no longer with the company and, according to AveXis, have not been involved in AveXis operations since May. Brian Kaspar has denied any wrongdoing. Page Bouchard, who has been with Novartis for 10 years, is taking over their roles.

Marks notes that gene therapy products are being evaluated for more than 800 different uses, developed by big pharma companies and small biotechs. “They all need to understand that the information that the agency gets needs to be accurate, truthful, and complete,” he told STAT. “And that means that it may take a little more time to get there.”