Following the news that the US Food and Drug Administration (FDA) has halted a trial of Novartis’s gene therapy Zolgensma due to safety concerns;

Fiona Chisholm, Managing Analyst at GlobalData, a leading data and analytics company, offers her view on this latest setback:

“Interim results reported for the STRONG trial earlier this month suggested that the company had a compelling case to expand access to Zolgensma (onasemnogene abeparvovec-xioi) in children up to five years of age, as patients aged 2–5 years achieved improvements in motor function, as measured by Hammersmith Functional Motor Scale-Expanded (HFMSE) scores, at 9.3 months of follow-up, which is nearly double the clinically meaningful threshold.

“However, the trial has been put on hold due to findings from a small study that identified evidence of dorsal root ganglia mononuclear cell inflammation in animals administered intrathecal Zolgensma, which can be associated with adverse sensory effects. Although no evidence of adverse sensory effects has been found in the human safety data to date, this latest development is likely to compound previously existing concerns relating to the safety of the gene therapy and represents a blow to Novartis’ strategy to supplant Biogen’s Spinraza (nusinersen) as the standard-of-care.

“Novartis’ Zolgensma campaign is still feeling the effects of a data manipulation controversy concerning the approval of intravenous Zolgensma. In August 2019, the FDA announced that Novartis and its subsidiary AveXis, had been aware that some preclinical data relating to the biologics license application had been manipulated prior to the therapy’s approval, although the companies waited until a month after approval to inform the agency. Although the gene therapy has remained on the market, the FDA has stated that had it been informed earlier the approval would have been delayed pending further investigation of the data issue. Additionally, even before this came to light, experts have expressed concerns about the long-term safety effects of administering adeno-associated virus (AAV) vectors to the human body.

“Although safety concerns relating to Zolgensma may impede initial uptake across the patient population and pose challenges to its expansion to new patient subsets, the gene therapy is still expected to emerge as a multi-blockbuster drug within the next decade due to its revolutionary one-time administration and strong efficacy profile.”