Two patients treated with Novartis’ gene therapy for the rare genetic disease Zolgensma have died, highlighting a known but rare risk of side effects associated with the drug and other genetic medicines.
Novartis said in an emailed statement that the children who died experienced acute liver failure about 5 to 6 weeks after the gene therapy infusion and within 10 days of starting tapering corticosteroids for liver problems. The company did not further specify when the deaths occurred, other than describing them as “recent patient deaths.” Novartis did say the cases were in Russia and Kazakhstan.The death toll was first reported on Thursday By Statistics.
Acute liver failure is a known complication of Zolgensma and is marked with a boxed warning in the drug’s prescribing information. The two deaths are the first deaths from acute liver failure associated with gene therapy, Novartis said.
“While this is important safety information, it is not a new safety signal, and we strongly believe in the overall favorable risk/benefit profile of Zolgensma, which has been used to date in over 2,300 patients worldwide in clinical trials, managed access programs , and in a commercial environment,” the company said.
Zolgensma treats spinal muscular atrophy (SMA), a rare muscle disease caused by a genetic mutation that results in insufficient levels of a protein critical for motor neuron survival. There are several types of SMA, but broadly speaking, the disorder causes progressive muscle weakness that worsens with age. In the most severe forms of SMA, the disease usually results in death by age 2 years.
Novartis Gene Therapies provide functional versions of mutated genes. The one-time treatment is designed to get the patient’s cells to produce the muscle protein they need. Zolgensma is delivered to cells by adeno-associated virus (AAV), a common vector for genetic drug delivery. Hepatotoxicity is a known risk of side effects for these engineered viruses. Such problems have been flagged in other clinical trials. nearly a year ago, Astellas Pharma reports that a fourth patient died in a study testing its gene therapy for X-linked myotube myopathy, A different neuromuscular disease. In this case, liver complications developed following administration of the experimental Astellas gene therapy.
No deaths reported in clinical trials leading to Zolgensma 2019 FDA ApprovalThese studies show that after treatment, many young children are able to sit, stand, and even walk without support—developmental milestones that are missed when the disease progresses without treatment. But results from clinical studies also point to high levels of liver enzymes that are a marker of drug toxicity.drug Label It also noted that since the drug was marketed, cases of liver injury and liver failure have been reported. The prescribing information recommends that clinicians monitor for such complications, which can be treated with corticosteroids.
Novartis said it was notifying health authorities and clinicians in the more than 40 markets where the drug was approved. The company added that it would update the drug label to specify reports of fatal acute liver failure. According to Novartis’ financial report, Zolgensma’s global sales in 2021 will be approximately $1.4 billion, up 47% from the previous year.
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