RARE Daily

Japan Approves Novartis’ Gene Therapy Zolgensma to Treat SMA  

March 20, 2020

Rare Daily Staff

The Japanese Ministry of Health, Labour and Welfare has approved Novartis’ gene therapy Zolgensma for the treatment of spinal muscular atrophy in patients under the age of two, including those who are pre-symptomatic at diagnosis.

Spinal muscular atrophy (SMA) is a rare genetic disease caused by a mutation in the SMN1 gene, which encodes the protein critical for the maintenance and function of specialized nerve cells called motor neurons. If there is not enough functional SMN protein, then the motor neurons die, leading to debilitating and often fatal muscle weakness. Infantile-onset SMA is the most severe and most common subtype of SMA. Children with this condition have problems holding their head up, swallowing and breathing. These symptoms may be present at birth or may present by the age of six months.

Zolgensma is a one-and-done gene therapy designed to address the genetic root cause of spinal muscular atrophy by providing a functional copy of the human SMN gene to halt disease progression through sustained SMN protein expression. It is approved to treat patients with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene. It is also approved to treat infants who are pre-symptomatic at diagnosis.

In Japan, SMA is considered an intractable disease, and approximately 15 to 20 SMA patients are expected to be eligible for treatment each year. Reimbursement by the health authority is expected by the end of June 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 percent 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 several trials that were designed to evaluate the efficacy and safety of a one-time IV infusion of Zolgensma in symptomatic SMA Type 1 patients less than six months of age at dosing, who had one or two copies of the SMN2 backup gene, or two copies of the SMN2 backup gene.

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 the long-term follow-up are now reaching five years of age. Interim results from the ongoing phase 3, open-label, single-arm study of a single, one-time IV infusion of Zolgensma in pre-symptomatic patients demonstrate rapid, age‑appropriate major milestone gain, reinforcing the critical importance of early intervention in SMA patients.

The most commonly observed side effects after treatment were elevated liver enzymes and vomiting.

In May 2019, the U.S. Food and Drug Administration 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 United States, and Novartis says almost all on-label patients have been approved by their payer for access to Zolgensma, which is priced at $2.1 million.


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