FDA approved Zolgensma in May for children under the age of two as a one-time treatment for spinal muscular atrophy, a rare genetic condition that affects about 30 new patients each month.
Spinal muscular atrophy is a muscle-wasting disease caused by a defect in a gene that ordinarily allows the body to maintain motor neurons. Without that gene functioning properly, infants usually die or must live on life support.
In clinical trials, Zolgensma appeared to halt the progress of spinal muscular atrophy. The gene therapy was priced at $2.1 million and is considered the most expensive drug in the world.
FDA investigates data manipulation claims
FDA in a statement said that on June 28, AveXis, a Novartis subsidiary that manufacturers Zolgensma, told the agency about a "data manipulation issue" that occurred in early stage testing of the drug. According to the New Times, the data manipulation occurred while researchers were testing two different strengths of the drug in mice.
Specifically, the report said that some records stating how long the mice lived "were different from the actual value," and in four cases, "discrepancies of greater than one day were noted (ranging from two to 19 days)."
According to FDA, AveXis became aware of the potential data manipulation in March but did not disclose the issue to FDA until June 28, nearly a month after FDA approved the drug.
Novartis in a statement said that once AveXis learned of the data manipulation, the company immediately began to investigate, and once it had "interim conclusions," it shared them with FDA. The company also noted that the affected data "are limited to an older process no longer in use."
Peter Marks, director of FDA's Center for Biologics Evaluation and Research, said, "It's unclear to us, at this point, exactly why this occurred." Marks said his main concern was that FDA received "data that was inaccurate … as part of their application and that led us to approve a product potentially sooner than we might have." The public "expects us to have accurate data when we approve products," he added.
Ned Sharpless, acting FDA commissioner, said in a tweet that "the agency will use its full authorities to take action."
In response to analysts' questions over the company's decision, Novartis CEO Vas Narasimhan on Wednesday further explained that the company wanted to know all the details before sharing the issue with FDA. "We understand the agency has a different perspective which we can respect," he said.
Narasimhan added, "We are committed to rebuilding trust with society, deeply for me, personally, all the way through the broader organization." However, he acknowledged that "it's a long, long road, and sometimes it's bumpy."
Zolgensma staying on the market
While FDA continues to investigate the matter, the agency made clear it believes Zolgensma should remain on the market.
FDA said that the data manipulation did not involve testing of Zolgensma in patients and that it's confident the drug is safe and should remain on the market. "The benefit-risk ratio is clearly in favor of allowing the product to remain on the market," Marks said.
Novartis in a statement said, "At no time during the investigation did the findings indicate issues with product safety, efficacy, or quality. We remain fully capable of releasing high-quality, fully compliant Zolgensma to patients in need" (Johnson, AP/New York Times, 8/6; Thomas, New York Times, 8/6; McGinley, Washington Post, 8/6; Thomas, New York Times, 8/7; Sagonowsky, FiercePharma, 8/7).