Novartis’ spinal muscular atrophy gene therapy Zolgensma made all kinds of headlines leading up to and following its approval. Now, it’s making just the kind of headlines no drug company wants to be caught up in.
On Tuesday, the FDA said Novartis submitted a drug application with manipulated data and didn’t inform regulators of the issue until one month after approval. The company was aware of the issues two months before the FDA greenlighted the drug, the agency says. If the regulator had been aware of the data manipulation, it would've had to delay its decision and strike up an investigation.
Acting FDA chief Ned Sharpless, M.D., tweeted that the agency "will use its full authorities to take action, if appropriate, which may include civil or criminal penalties."
Still, the FDA believes the drug should remain on the market. Peter Marks, M.D., Ph.D., director of FDA’s Center for Biologics Evaluation and Research, said in a statement that the agency’s concerns are “limited to only a small portion of the product testing data" relating to testing in animals, not in humans.
"The assays in question were used for initial product testing and are not currently used for commercial product release. 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 said in a statement, adding that "the data in question were a small portion of our overall submission and are limited to an older process no longer in use."
Following an investigation, Wilson Bryan, M.D., director of the agency’s Office of Tissues and Advanced Therapies, wrote in a memo that he still believes Zolgensma is “safe, pure, and potent” for its approved population.
But, he wrote, Novartis’ AveXis unit “appears to have become aware of the data manipulation as early as March 14, 2019." The drug won approval on May 24, and the company “did not inform FDA of the issue until over a month after the BLA approval," Bryan wrote. AveXis told the FDA in late June that its "personnel had manipulated data from an in vivo murine potency assay," Bryan wrote in the memo.
“If AveXis had informed FDA of this issue prior to the BLA approval, I believe that the approval would have been delayed beyond the PDUFA goal date of May 31, 2019,” Bryan wrote, saying the agency would've had to strike up a probe. In the end, though, Bryan believes the FDA would’ve approved the application.
Novartis acquired AveXis in April last year to bolster its presence in gene therapies, with Zolgensma representing the primary drug candidate from the takeout. The drug now carries the world's highest pharma price tag at $2.125 million and treats certain SMA patients under 2.
Tuesday's news is only the latest regulatory misstep for Novartis, which has been working to bolster its compliance following a number of scandals around the world in recent years. From 2013 to 2015, scandals erupted in Japan as authorities discovered Novartis manipulated data and failed to report side effects.
The drugmaker has also been hit with bribery allegations in various countries and suffered through its embarrassing episode with President Donald Trump's former personal attorney Michael Cohen last year. Upon taking the CEO post last year, Vas Narasimhan has made compliance a priority, but the Zolgensma issue shows the company still has some work to do in the area.