USFDA placed a partial hold on clinical trials for intrathecal administration of AVXS-101. The announcement follows an AveXis communication to health authorities and clinical trial investigators based on findings from a small, AveXis-initiated pre-clinical study in which animal findings showed dorsal root ganglia (DRG) mononuclear cell inflammation, sometimes accompanied by neuronal cell body degeneration or loss. This partial hold by the FDA does not impact marketed Zolgensma or AVXS-101 intravenous (IV) clinical trials.
AveXis is studying AVXS-101 intrathecal administration in patients with spinal muscular atrophy (SMA) Type 2. The partial hold impacts enrollment in the high dose cohort of the STRONG trial, an ongoing, open-label, dose-comparison, multi-center trial designed to evaluate the efficacy, safety and tolerability of one-time intrathecal administration of AVXS-101. The low and mid dose cohort enrollment has previously been completed and interim results have been presented.
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. DRG inflammation can be associated with sensory effects. Of note, we have completed a thorough review of human safety data from all available sources to date and no adverse effects related to sensory changes have been seen in AVXS-101 intrathecal or Zolgensma. We are working with health authorities to confirm further guidance to clinical investigators.