Intrathecal Trials of AVXS-101 (Zolgensma) in SMA Halted

Megan Brooks

October 31, 2019

The US Food and Drug Administration (FDA) has placed a partial hold on clinical trials testing intrathecal administration of onasemnogene abeparvovec-xioi (AVXS-101, Zolgensma , AveXis Inc, a Novartis company) because of safety concerns found in an animal study.

Zolgensma intravenous infusion is not impacted and remains available in the US, the company said. 

Last spring, as reported by Medscape Medical News, this product became the first gene therapy approved in the US for children younger than age 2 with spinal muscular atrophy (SMA), a rare genetic disease that can lead to paralysis, breathing difficulty, and death.

Zolgensma is given as a single one-time intravenous infusion.

AveXis is studying the efficacy, safety, and tolerability of a one-time intrathecal administration of AVXS-101 in patients with SMA type 2.

The partial hold on intrathecal administration of the therapy is based on findings in animals suggesting an association with dorsal root ganglia (DRG) mononuclear cell inflammation, sometimes accompanied by neuronal cell body degeneration or loss, Novartis said in a news release.

"The clinical significance of the DRG inflammation observed in this pre-clinical animal study is not known and was not seen in prior animal studies with AVXS-101," Novartis said.

DRG inflammation can be associated with sensory effects, but Novartis said a thorough review of all available human safety data found no adverse effects related to sensory changes with AVXS-101 intrathecal or Zolgensma.

Novartis said it is working with the FDA to determine next steps to release the partial hold and resume dosing in the AVXS-101 intrathecal trials.

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