- FDA placed a partial hold on AVXS-101 intrathecal clinical trials for SMA patients based on findings in a small pre-clinical animal study
- Adverse events that might be expected from the pre-clinical findings have not been seen in a thorough review of human safety data from all available sources to date
- Zolgensma (onasemnogene abeparvovec-xioi) 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
Basel, October 30, 2019 - Novartis today announced the United States Food & Drug Administration (FDA) 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.
We will continue to closely monitor for any reports of related safety events in patients. We remain confident that the overall benefit-risk profile for patients on treatment is favorable and we continue to advance our AVXS-101 intravenous clinical studies. We will work diligently with 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, a rare and devastating genetic disease.
About AVXS-101 Intrathecal Administration
Investigational IT administration of AVXS-101 is currently being evaluated in patients with SMA Type 2 in a Phase 1/2 clinical trial.
Zolgensma in the United States
Zolgensma (onasemnogene abeparvovec-xioi) is an adeno-associated virus vector-based gene therapy indicated for the treatment of pediatric patient less than 2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene.
Limitation of Use
The safety and effectiveness of repeat administration of Zolgensma have not been evaluated.
The use of Zolgensma in patients with advanced SMA (e.g., complete paralysis of limbs, permanent ventilator-dependence) has not been evaluated.