Novartis announced this morning that the Food and Drug Administration (FDA) in the US has placed a partial hold on AVXS-101 intrathecal clinical trials for SMA patients based on findings in a small pre-clinical animal study.
Zolgensma® , also known as AVXS-101 intravenous administration is not impacted and remains available in the US. Novartis is working with FDA to determine next steps to release partial hold and resume dosing in the AVXS-101 intrathecal trials.
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.
AveXis is studying AVXS-101 intrathecal administration in patients with 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. AveXis/ Novartis are working with health authorities to confirm further guidance to clinical investigators.
AveXis will continue to closely monitor for any reports of related safety events in patients. They remain confident that the overall benefit-risk profile for patients on treatment is favourable and they continue to advance their AVXS-101 intravenous clinical studies. They will work diligently with the FDA to identify any additional actions necessary to resume dosing in the AVXS-101 intrathecal clinical trials.
AveXis and Novartis remain committed to researching and developing gene therapies for SMA.