The Intrathecal AVXS-101 Clinical Trials For SMA Have Been Put On Hold In The USA
30 October 2019
On 30th October, Novartis announced that the Food and Drug Administration (FDA) in the US has placed a partial hold on clinical trials of intrathecal (lumbar puncture) injections of AVXS-101 for SMA patients. This is based on findings in a small pre-clinical animal study. Trials and development of this treatment is by AveXis, which is separately run but owned by Novartis who manage all communications. Novartis is now working with the FDA to determine the next steps and additional actions needed to release the partial hold and resume dosing in the AVXS-101 intrathecal trials being run by AveXis.
This development does not affect the intravenous (IV) administration of Zolgensma, also known as AVXS-101. This IV treatment remains available in the US. It is currently being considered by the European Medicines Authority (EMA) for licensing and, provided this is granted, NICE will consider whether to recommend it for NHS funding at its first committee meeting on 26th March 2020.
The announcement follows an AveXis communication to health authorities and clinical trial investigators based on findings from a small, AveXis-initiated, pre-clinical study; intrathecal AVXS-101 injections into animals resulted in an inflammation response in sensory nerves (called the dorsal root ganglia (DRG)) sometimes accompanied by sensory nerve cell damage or loss.
AveXis is studying AVXS-101 intrathecal administration in patients with SMA Type 2. The partial hold impacts enrollment in the high dose group of the STRONG trial, an ongoing, open-label, dose-comparison, multi-centre trial designed to evaluate the efficacy, safety and tolerability of one-time intrathecal administration of AVXS-101. The low and mid dose group enrollment has previously been completed and interim results have been presented.
The clinical significance of the sensory nerve (DRG) inflammation observed in this pre-clinical animal study is not known and was not seen in prior animal studies with AVXS-101. Sensory nerve inflammation can be associated with effects on sensation.
Novartis state that they 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 with intrathecal or intravenous administration of AVXS-101. 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 (IV) clinical studies.