SMA Gene Therapy Zolgensma Approved in Japan
24 March 2020
Novartis announced on 19th March 2020 that the Japanese Ministry of Health, Labour and Welfare approved ZolgensmaTM (also known as onasemnogene abeparvovec) for the treatment of SMA in patients under the age of two, including those who are pre-symptomatic at diagnosis.
ZolgensmaTM is a single-dose gene therapy designed to address the genetic cause of SMA by replacing the SMN1 gene, which is missing or not working in patients. The gene therapy is administered by a single injection into the bloodstream. This results in delivery of a new working copy of the SMN1 gene into patient cells, which can help to limit disease progression.
To increase chances of success, patients receiving ZolgensmaTM must be negative for elevated levels of antibodies against the particular virus (called AAV9) used to deliver the SMN1 gene. Approximately 15-20 SMA patients in Japan are expected to be eligible for treatment each year.
This approval was based on the results from several clinical trials:
- Phase 1 START
- START Long-term follow-up
- Phase 3 STR1VE-US
- Phase 3 SPR1NT
- Phase 1/2 STRONG (intrathecal injection) trials
START and STR1VE-US were designed to evaluate the efficacy and safety of a single injection of ZolgensmaTM into the bloodstream of symptomatic SMA Type 1 patients aged less than 6 months at dosing. Patients in the START trial had one or two copies of the SMN2 backup gene, while patients in the STR1VE-US trial had exactly two copies. ZolgensmaTM treatment resulted in rates of survival never seen in the natural history of the disease, rapid motor function improvement and milestone achievement, including the ability to sit without support, which is something never achieved in untreated patients. Patients in the START Long-term follow-up study are now reaching five years of age.
Interim results from the ongoing SPR1NT trial, a Phase 3, open-label study of ZolgensmaTM treatment in pre-symptomatic SMA patients (aged less than 6 weeks at dosing), demonstrate rapid, age‑appropriate major milestone gain, reinforcing the critical importance of early intervention in the disease.