Zolgensma Approved For SMA Treatment in Japan

The Japanese Ministry of Health, Labour and Welfare approved Zolgensma (onasemnogene abeparvovec-xioi) for the treatment of spinal muscular atrophy (SMA) patients under the age of two, Novartis announced.

The approval includes toddlers and newborns who are pre-symptomatic at diagnosis, meaning those who have not yet shown symptoms. Eligible patients for treatment must not show elevated antibodies against adeno-associated virus (AAV) 9, the viral carrier system used to deliver Zolgensma to cells.

“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 2 in more than 90% of cases,” Kazunari Tsunaba, president and representative director of Novartis Pharma, said in a press release.

“A one-time dose of Zolgensma has the potential to make a truly transformative impact on this life-threatening disease,” Tsunaba said. “This is an important day for the children and families in Japan impacted by SMA, both today and in the future.”

Zolgensma, the first gene therapy for SMA and the second therapy to be approved for the disease, is designed to be a one-time treatment. It is made of the capsid of an engineered virus  — AAV9 — that carries a working copy of the the SMN1 gene to the patient’s motor neurons.

The therapy is administered as a single intravenous (IV) infusion. Its approval was based on a series of clinical trials that showed improved overall motor skills, achievement of motor milestones such as sitting or standing unassisted, and rates of survival previously unseen in the natural history of the disease.

Approval in Japan was based on data from the Phase 1 START trial (NCT02122952) and its long-term follow-up study (NCT03421977), the completed Phase 3 STR1VE-US trial (NCT03306277), the ongoing SPR1NT Phase 3 clinical trial (NCT03505099) assessing Zolgensma’s efficacy in presymptomatic infants, and the Phase 1/2 STRONG trial (NCT03381729) assessing Zolgensma given directly into the spinal canal (intrathecal delivery).

The STRONG trial has been put on partial hold by the U.S. Food and Drug Administration due to issues concerning inflammation seen in primates in a preclinical study. While this hold stopped both treatment and further enrollment for a high-dose STRONG group, treatment at low and middle doses was complete with no evidence of safety concerns.

“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,” said Dave Lennon, president of Novartis’ AveXis subsidiary. “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.”

Novartis expects about 15 to 20 patients in Japan will be eligible for Zolgensma treatment every year. Reimbursement from the Japanese authority is expected in the first half of 2020. If the agreement moves forward, the therapy will be available at that time.