The Food and Drug Administration (FDA) has placed a partial hold on clinical trials for the intrathecal administration of AVXS-101 (AveXis, a Novartis Company) in patients with spinal muscular atrophy (SMA) Type 2. 

The partial hold was based on findings from a small, AveXis-initiated pre-clinical study that showed dorsal root ganglia (DRG) mononuclear cell inflammation in animal models. DRG inflammation was sometimes accompanied by neuronal cell body degeneration or loss. This reaction was not observed in previous animal studies with AVXS-101, and the clinical impact is unknown. The partial hold does not affect ongoing intravenous (IV) clinical trials for AVXS-101, marketed as Zolgensma.

Currently, AveXis is evaluating AVXS-101 in the phase 1 STRONG trial as a one-time intrathecal administration for the treatment of patients with SMA Type 2. In the open-label trial, patients were assigned to 3 treatment arms: low, mid, and high dose cohorts. The partial hold will only impact the ongoing high-dose cohort as enrollments for the low and mid dose cohorts have been completed with interim results already presented.

Regarding safety, the Company stated that a thorough review of human safety data to date showed no adverse events related to sensory changes with AVXS-101 intrathecal or Zolgensma. In a press release, Novartis stated that the Company is working with the FDA to determine next steps so that trials evaluating intrathecal administration can resume.

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Zolgensma (onasemnogene abeparvovec-xioi) was approved in May 2019 for the treatment of children less than 2 years of age with SMA with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene, administered via IV infusion.

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