Novartis AG said a final autopsy report showed that the death of an infant in a phase 3 study was unrelated to its $2.1 million gene therapy Zolgensma, which is approved in the U.S. to treat a rare debilitating muscle disorder.
AveXis Inc., which Novartis acquired in 2018, reported the information along with interim data from phase 3 studies SPR1NT and STR1VE, and interim results from a long-term follow-up of a phase 1 study called START. The companies are under investigation from the U.S. Food and Drug Administration for falsifying preclinical data for Zolgensma.
Phase 3 STR1VE program
The STR1VE program includes the STR1VE-US and STR1VE-EU trials to evaluate the efficacy and safety of a single, one-time IV infusion of Zolgensma in patients with spinal muscular atrophy, or SMA, Type 1 — a neuromuscular disorder that affects voluntary muscle movement and leads to difficulty in breathing, swallowing, speaking and walking.
Children with SMA type 1 have a 50% survival rate at 10 months and about an 8% survival at 20 months.
Results showed that Zolgensma prolonged event‑free survival — meaning subjects did not experience complications or required ventilation support for breathing — compared to natural history, and improved motor function in patients with SMA Type 1. New interim data from the ongoing STR1VE-EU trial show that nine out of the 10 patients who reached 10.5 months of age or experienced an event did so without permanent ventilation.
AveXis said the death of a child in the STR1VE-EU trial was caused by hypoxic-ischemic brain damage, with respiratory tract infection being the underlying cause. The company added that there was no evidence of an inflammatory central nervous system process or toxic or treatment-related brain damage.
The final autopsy report, however, indicated that Zolgensma could have potentially contributed to abnormal liver function and low blood pressure.
In the STR1VE-US trial, 20 of the 22 patients enrolled in the study were alive without permanent ventilation.
Phase 3 SPR1NT study
In this study, AveXis is evaluating Zolgensma in spinal muscular atrophy patients at least six weeks old who have not yet shown symptoms of the disease and have two or three copies of the SMN2 gene. Spinal muscular atrophy is caused by a defective or missing SMN1 gene in the body, and nearly all people, including those with the disease, have a second, virtually duplicate gene known as SMN2.
The company said all of the 22 patients being evaluated were alive and free of permanent ventilation as of May 31, the cut-off date for an interim analysis.
START follow-up study
AveXis evaluated Zolgensma in a phase 1 trial, dubbed START, in SMA Type 1 patients with the onset of clinical symptoms before six months of age. At the close of the two-year study, all 12 patients in a particular group were alive and free of permanent ventilation.
Follow-up data from 10 patients who agreed to be monitored further showed they were alive and continuing to maintain developmental milestones.
The average age of patients was 4.2 years, and the average time since gene therapy treatment started was 3.9 years.
