A rare, genetic neuromuscular disease caused by a lack of a functional SMN1 gene, SMA results in the rapid and irreversible loss of motor neurons, affecting muscle functions, including breathing, swallowing and basic movement.3 Approximately 60% of all SMA is Type 1. Zolgensma is a one-time gene therapy designed to address the genetic root cause of the disease by replacing the function of the missing or nonworking SMN1 gene. Zolgensma is administered during a single intravenous (IV) infusion, delivering a new working copy of the SMN gene into a patient’s cells, halting disease progression. Approximately 15-20 SMA patients in Japan are expected to be eligible for treatment each year. Reimbursement with MHLW is expected by the end of 1H20 and, pending agreement, Zolgensma will be available at that time.
“SMA is the leading genetic cause of infant death and, if left untreated in its most common form, Type 1, leads to death or the need for permanent ventilation by the age of two in more than 90% of cases,” said Kazunari Tsunaba, president and representative director, Novartis Pharma. “A one-time dose of Zolgensma has the potential to make a truly transformative impact on this life-threatening disease. This is an important day for the children and families in Japan impacted by SMA, both today and in the future.”
Approval is based on the Phase 1 START, START Long-term follow-up, Phase 3 STR1VE-US, Phase 3 SPR1NT and Phase 1/2 STRONG (intrathecal injection) trials. START and STR1VE-US were designed to evaluate the efficacy and safety of a one-time IV infusion of Zolgensma in symptomatic SMA Type 1 patients <6 months of age at dosing, who had one or two copies of the SMN2 backup gene, or two copies of the SMN2 backup gene, respectively. Zolgensma demonstrated rates of survival never seen in the natural history of the disease; rapid motor function improvement, often within one month of dosing; and milestone achievement, including the ability to sit without support, a milestone never achieved in untreated patients. Patients in START Long-term follow-up are now reaching five years of age. Interim results from the ongoing SPR1NT trial, a Phase 3, open-label, single-arm study of a single, one-time IV infusion of Zolgensma in pre-symptomatic patients (<6 weeks at age of dosing) genetically defined by bi-allelic deletion of SMN1 with 2 or 3 copies of SMN2 demonstrate rapid, age‑appropriate major milestone gain, reinforcing the critical importance of early intervention in SMA patients. It is imperative to diagnose SMA and begin treatment, including proactive supportive care, as early as possible to halt irreversible motor neuron loss and disease progression.
The most commonly observed side effects after treatment were elevated liver enzymes and vomiting. Acute serious liver injury and elevated aminotransferases can occur. Patients with pre-existing liver impairment may be at higher risk. Prior to infusion, physicians should assess liver function of all patients by clinical examination and laboratory testing. And, they should administer systemic corticosteroid to all patients before and after treatment, and then continue to monitor liver function for at least 3 months after infusion.
“Zolgensma provided rapid, significant and clinically meaningful therapeutic benefit in symptomatic and pre-symptomatic SMA, including prolonged event-free survival and achievement of motor milestones never seen before in natural history of the disease. We are proud to bring the first gene therapy for SMA to Japan, and especially of the transformational impact Zolgensma will have on the children and families affected by SMA,” said Dave Lennon, president, AveXis.
In May 2019, the U.S. Food and Drug Administration (FDA) approved Zolgensma for the treatment of pediatric patients less than two years of age with SMA with bi-allelic mutations in the SMN1 gene. Approximately 400 patients have been treated with Zolgensma, including clinical trials, commercially and through the managed access program in the U.S. In the U.S. nearly all on-label patients have been approved by their payer for access to Zolgensma. AveXis is pursuing registration in close to three dozen countries with a Committee for Medicinal Products for Human Use opinion expected in 1Q 2020 and regulatory decisions anticipated in Switzerland, Canada and Australia in late 2020 or early 2021.
Source: Company Press Release