Novartis reports that the FDA has placed a partial hold on intrathecal trials of the world’s most expensive drug ($2 million per treatment)—a gene therapy called Zolgensma for spinal muscular atrophy (SMA) patients. Apparently, new issues have emerged involving a small preclinical animal study.

TrialSite News has discussed the Novartis AveXis acquisition as part of a fundamental shift in strategy away from “volume to value. Zolgensma represents the cutting-edge in gene-based therapy affording heretofore not possible health care—hence the $2+ million price tag for this gene therapy for SMA patients under 2 years old.

We reported on Novartis’ withholding of material data only to disclose post-FDA approval of Zolgensma. Although the concerning underlying data originated with the acquired company (AveXis) the decision to withhold material data was made post-acquisition. Partially it is believed Novartis chose not to disclose because the data withheld didn’t affect Zolgensma’s safety or efficacy. 

The latest reported issue was picked up on by RAPSZachary Brennan who reports that AveXis safety management team representatives were presented with safety findings and the company “determined at that time that the safety finding should be included in the annual update of the investigator brochure planned for September 2019. Unfortunately, a mistake was made, and this update was not implemented.” Brennan noted that the omission was identified as part of the Form 483 response from August and that a company spokesman declared “This omission was identified and the issue quickly assessed and managed pursuant to existing Novartis safety processes and we notified health authorities and clinical trial investigators.”

Apparently, the issues were associated with a pre-clinical study associated with 12 non-human primates where dorsal root ganglia (DRG) mononuclear cell inflammation was observed. This can sometimes be associated with neuronal cell body degeneration or loss. Novartis reported that the clinical significance of the DRG inflammation observed in the pre-clinical animal study isn’t known and wasn’t observed in previous animal studies. Mr. Brennan reported that a Novartis spokesperson commented that they “will continue to closely monitor for any reports of related safety events in patients” and of course rigorously “work diligently with the FDA to identify any additional actions necessary to resume dosing in the AVXS-101 intrathecal clinical trials.”

An FDA partial hold precludes any impact on the marketing of Zolgensma or materially impede other clinical trials.

Doing Well

It was recently reported Zolgensma is doing well with sales. Novartis generated $160 million must between July and September 2019 as 100 infants have been treated in the first full quarter of the availability of the drug reported Biopharma Dive’s, Andrew Dunn. The math points to an average treatment price of $1.6 million per infant. The FDA late Summer 2019 issued a statement on data accuracy for the recently approved gene therapy. For now, they have limited concerns about the product and believe it should remain on the market—e.g. the data quality issues have been de minimis in actual impact on safety.

We are entering a brave new world of drug therapies. Heretofore not possible treatments including potential genetic cures boggle many a mind. TrialSite News focuses on bringing transparency to the world of clinical research—to benefit all. We will monitor how these 100+ patients are doing for real-world assessment of this powerful new gene therapy—as that data becomes available.

Source: The Food Drug Administration

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