- The European Medicines Agency is considering advising doctors to more closely monitor patients treated with Novartis’ gene therapy Zolgensma for liver injury, according to a notice put out Friday.
- The EMA’s safety committee, known as PRAC, this week discussed sending physicians letters with additional information on the safety risk and how to manage it. Their recommendation to do so comes months after two children died from acute liver injury followed treatment with the gene therapy, which is for the neuromuscular condition spinal muscular atrophy.
- The proposed “direct healthcare provider communication” will be forwarded to two other EMA committees for formal adoption by the agency.
In its most severe form, spinal muscular atrophy is usually fatal before the age of two. Zolgensma, which was proven powerfully beneficial in clinical testing, won approval in Europe in 2020, one year after its clearance in the U.S.
Testing showed Zolgensma can keep infants alive for longer and help them reach developmental milestones, such as sitting upright without support, that they otherwise would be unlikely to achieve.
In the U.S., Zolgensma already carries a “black box” warning for acute serious liver injury and acute liver failure. After the two deaths last August, Novartis notified the FDA and regulators in other countries where the drug is used. The company defended its treatment, noting that it remains confident in the drug’s risk/benefit profile.
Gene therapy can present risks to the liver because the inactivated viruses drugmaker use to shuttle genes into the body often end up in the organ, potentially causing damage when given at high doses.
Two other cases of acute liver failure were previously reported in patients taking Zolgensma, but those patients were treated with steroids and continued to make gains months after.
The communication under discussion at the EMA would instruct doctors to look for suspected liver injury after treatment and give additional advice for how to taper steroid treatment following infusion. It would also call on physicians to “promptly assess” patients with worsening liver function tests.
Zolgensma is one of three drugs recently approved for spinal muscular atrophy, before which there were no available treatments. The gene therapy is used in infants and younger children, while drugs from Roche and Biogen can be used in older children and adults with less severe forms of the disease.
Zolgensma is one of Novartis’ top-selling medicines, although sales have been slowing. The company has been working to improve newborn screening for the disease in Europe, where it is less common than it is in the U.S.