The US Food and Drug Administration (FDA) has placed a partial hold on clinical trials for the intrathecal administration of Novartis’ Zolgensma (onasemnogene abeparvovec-xioi), a gene therapy, or AVXS-101.

AveXis, a Novartis company, is studying AVXS-101 intrathecal administration in patients with spinal muscular atrophy (SMA) Type 2, a rare neuromuscular disorder. Earlier this year (May 2019), Zolgensma was approved by the FDA for SMA in children less than two years old with intravenous infusion. The partial hold impacts enrollment in the high-dose cohort of 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. This partial hold by the FDA does not impact marketed Zolgensma or AVXS-101 intravenous clinical trials.

This is another setback for Novartis for its gene-therapy product. Earlier this year (August 2019), the FDA issued a statement addressing concerns related to product-testing data used to support the production process in the biologics license application for Zolgensma. That followed a voluntary self-disclosure in June 2019 by AveXis to the FDA and to other health authorities about a data-manipulation issue that impacted the accuracy of certain data from product testing performed in animals submitted in the biologics license application reviewed by the FDA. The agency’s concerns related only to the product-testing data used to support the production process for the product and not the agency’s clinical assessment of the product.

The announcement of the partial clinical hold follows a AveXis communication to health authorities and clinical trial investigators based on findings from a small, AveXis-initiated preclinical study in which animal findings showed dorsal root ganglia (DRG) mononuclear cell inflammation, sometimes accompanied by neuronal cell body degeneration or loss. The clinical significance of the DRG inflammation observed in this preclinical animal study is not known and was not seen in prior animal studies with AVXS-101.

Novartis says it will continue to closely monitor for any reports of related safety events in patients and is working with health authorities to confirm further guidance to clinical investigators.

Source: Novartis