Novartis Korea said Friday that the Ministry of Food and Drug Safety has approved Zolgensma, gene therapy for spinal muscular atrophy (SMA).

The Ministry of Food and Drug Safety has approved Novartis' spinal muscular atrophy treatment, Zolgensma, as Korea's 1st gene therapy for the illness.
The Ministry of Food and Drug Safety has approved Novartis' spinal muscular atrophy treatment, Zolgensma, as Korea's 1st gene therapy for the illness.

Hospitals can use the drug to treat SMA Type 1 patients with a double allelic mutation in the SMN1 gene or three or fewer copies of the SMN Type 2 gene.

The ministry based its approval on various phase 3 clinical trials for patients with type 1 SMA, including a phase 3 STR1VE study, a phase 1 START study, and a phase 3 SPRINT study on SMA Type 2 patients diagnosed before symptom onset.

In the STR1VE clinical study, the company confirmed that Zolgensma significantly increased the event-free survival up to the unprecedented level of 14 months, the primary endpoint. In the 18th month, 20 patients (91 percent) survived without an assistive respiratory system, and 19 patients (86 percent) could eat without non-oral assistance, such as feeding tubes.

In the START study, patients treated with Zolgensma could sit without assistance, a stage of motor development that was unavailable for SMA patients who did not receive treatment.

As a result of the long-term follow-up of this study, the company confirmed efficacy that lasted more than 6.2 years after administration. Two patients could walk without assistance, and another two could stand with help.

In the SPRINT study still going on, the company has confirmed four patients with two SMN Type 2 gene copy (Cohort 1) and six patients with three SMN Type 2 gene copy (Cohort 2) could walk without assistance, and 11 and 13 patients in each cohort could sit without the aid for more than 30 seconds in June 2020.

"Zolgensma is the first and only gene replacement therapy approved in Korea that can completely cure SMA through a one-time intravenous administration," the company said. "By providing a functional replacement for the defective or defective SMN1 gene, it can prevent the progression of SMA by solving the root cause of the disease."

Zolgensma also improves motor function that is impossible to improve in natural conditions for severe SMA patients who have a high fatality rate due to muscle degeneration.

The company stressed that, unlike existing treatments that require lifetime treatments, the drug could improve the quality of life of patients and families with a single dose.

"Just a few years ago, infant patients with serious often required permanent respiratory help or death, but the recent introduction of several gene therapies has improved the patient's symptoms,” Professor Choi Jong-hee of Seoul National University Hospital said. “The development of a gene replacement therapy that can treat the root cause of SMA with only a one-time administration, such as Zolgensma, is very significant in treating rare diseases.”

As Novartis has confirmed the efficacy and safety of Zolgensma for more than six years through several clinical trials and the drug's efficacy on local patients is also good, the drug will further improve the quality of life of patients, Choi added.

According to experts, however, there are concerns that the drug, which has not received a price tag in Korea yet, is one of the most expensive drugs in the world. The drug has a price tag of $2.1 million (about 2.3 billion won) in the U.S.

SMA is a rare, fatal genetic disease in which muscles gradually atrophy due to a lack of mutation of the typical SMN Type 1 gene and is one of the leading causes of infant mortality. As the disease progresses, all muscles become weaker, which can be life-threatening as it affects that patient's ability to eat, move, and breath.

The disease occurs in about 1 in 10,000 newborns worldwide. Type 1, which accounts for about 60 percent of SMA patients, is the most severe. According to Novartis, 90 percent of patients with SMA Type 1 die before age two without any treatment.

Zolgensma works by inserting a functional replacement of the SMN1 gene in the patient through a carrier called a vector, delivering them to motor neurons in the body.

The SMN1 gene replacement, which usually lands in the patient's body, sits independently of the existing gene and produces the SMN protein essential for motor neurons in the body.

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