[Updated, 7:12 pm ET, see below] The FDA on Tuesday said that some data supporting the spinal muscular atrophy gene therapy Zolgensma was “manipulated” before its May 24 approval and that its manufacturer, Novartis (NYSE: NVS) subsidiary AveXis, knew about it.
The FDA stopped short of saying Zolgensma should be pulled from the market, but is nonetheless investigating the matter and threatened potential legal action.
An FDA memo issued alongside the Tuesday statement reveals that a member of AveXis, the Zolgensma developer that Novartis acquired in 2018, called the agency in June to say that the company “had manipulated data.” That issue “impacts the accuracy of certain data” from a test in mice that the agency scrutinized during its review process. That, in turn, could alter how the Phase 1 clinical trial results and other animal tests supporting Zolgensma are interpreted.
Still, the FDA said that its concerns surround a “small portion of product testing data” that support the method Novartis uses to manufacture Zolgensma. There is no evidence that AveXis manipulated clinical data from patients, for instance, so the agency’s opinion of the safety or effectiveness of Zolgensma hasn’t changed. The FDA “remains confident that Zolgensma should remain on the market.” But it cautioned that an investigation is underway and the agency may “amend [its review] as appropriate.”
What’s more, the FDA said that AveXis was aware of the problem before Zolgensma was approved. It didn’t tell the FDA until afterwards. The FDA will “use its full authorities to take action, if appropriate, which may include civil or criminal penalties,” it said in the statement.
[Updated with comments from Novartis] Novartis, in a statement issued Tuesday evening, said AveXis “voluntary self-disclosed” the issue to the FDA after it “had become aware of allegations of data manipulation.” Novartis investigated the issue internally as well and shared its findings with the FDA. Novartis noted that the data in question were related to an “older process no longer in use.”
The Swiss company added that it is “fully confident in the safety, quality and efficacy” of Zolgensma and will work with the FDA to address any “quality gaps” through the agency’s investigation. Novartis doesn’t expect the situation to delay any of its ongoing Zolgensma regulatory filings or development programs.
The nonprofit SMA patient advocacy group Cure SMA said it is “investigating the issue and will report when we have further details.”
Zolgensma is one of just two gene therapies approved in the U.S. Gene therapies offer the promise of long-lasting effects, if not outright cures, through a single treatment. But it’s unclear how long they’ll last, and companies and the healthcare system writ large are grappling with how to pay for them.
The FDA, for instance, cleared Zolgensma for babies under two years old with SMA, a potentially deadly rare genetic disease. That complicated matters for patients and payers because SMA has a wide range of subtypes, but Novartis so far has provided only early indications that Zolgensma might help patients beyond those with Type 1, the most severe form of the disease. What’s more, an established therapy, nusinersen (Spinraza), from Biogen (NASDAQ: BIIB), is available. The launch of Zolgensma marks the first time a gene therapy has gone head-to-head with an established product.
Novartis priced Zolgensma at $2.125 million, to be paid over several yearly installments. Reports have surfaced that some payers have made it difficult for patients to get access to Zolgensma, though Novartis has downplayed those concerns. Will news of manipulated data complicate matters, making it even harder for some patients to get access? Raymond James analyst Steven Seedhouse hinted at such a prospect in a research note, especially “given these optics, which could become more than optics if the data manipulation problem runs deeper.”
Biogen shares ticked up about 2 percent in trading on Tuesday.