RARE Daily

SMA Gene Therapy Zolgensma Granted Conditional Approval in Europe

May 20, 2020

The European Commission has granted conditional approval for Novartis’ gene therapy Zolgensma for the treatment of patients with the rare, genetic, neuromuscular condition spinal muscular atrophy.

Photo: Dave Lennon, president of AveXis

The approval of Zolgensma was for people with a bi-allelic mutation in the SMN1 gene and a clinical diagnosis of SMA type 1, or for patients with SMA with a bi-allelic mutation in the SMN1 gene and up to three copies of the SMN2 gene. It covers babies and young children with SMA who weigh up to 46.2 pounds, which according to a natural history study, covers almost all children under the age of five.

Approximately 550 to 600 infants are born in Europe each year with SMA caused by a lack of a functional SMN1 gene. The condition causes the rapid and irreversible loss of motor neurons, affecting muscle functions, including breathing, swallowing, and basic movement. It is the leading genetic cause of infant death. If left untreated, SMA type 1 leads to death or the need for permanent ventilation by the age of two in more than 90 percent of cases.

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. Administered during a single, intravenous infusion, Zolgensma delivers a new working copy of the SMN1 gene into a patient’s cells, halting disease progression.

“The EC approval of Zolgensma is a significant milestone for the SMA community, and further underscores the substantial clinical value of the only gene therapy for SMA, bringing new hope to those impacted by this rare, but devastating disease.” said Dave Lennon, president of AveXis, the Novartis subsidiary that developed Zolgensma. “Even under the current pandemic conditions, the urgent need to treat SMA has resulted in access pathways in France and Germany for Zolgensma, a potentially life-saving medicine delivered in a single dose.”

The EC approval is based on the completed phase 3 STR1VE-US and phase 1 START trials that evaluated the efficacy and safety of a one-time IV infusion of Zolgensma in symptomatic SMA Type 1 patients younger 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, respectively. STR1VE-EU, a comparable phase 3 study is ongoing.

Zolgensma demonstrated prolonged event-free survival; rapid motor function improvement, often within one month of dosing; and, sustained milestone achievement, including the ability to sit without support, crawl and walk independently—milestones never achieved in untreated type 1 patients and sustained for five years post-dosing.

Additional supportive data included 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 younger than six weeks of age at time of dosing) genetically defined by bi-allelic deletion of SMN1 with 2 or 3 copies of SMN2. These data 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.

European approval of Zolgensma comes one year after its approval in the United States and Novartis says that more than 500 patients have been treated with the gene therapy, which was priced at $2.1 million, in clinical trials, commercially, and through a managed access program.

AveXis in discussions with EU governments and reimbursement agencies to agree on terms of a “Day One” access program to enable rapid access in all EU countries. Designed to work within existing, local pricing and reimbursement frameworks, the “Day One” access program offers ministries of health and reimbursement bodies a variety of flexible options that can be implemented immediately to support swift access and broad reimbursement. Immediate access to Zolgensma, aligned to the label, is available in France through the ATU framework and expected shortly in Germany.

Zolgensma has also been approved for use in Japan, and AveXis is pursuing registration in close to another three dozen countries with regulatory decisions anticipated in Switzerland, Canada, Australia, Argentina, South Korea and Brazil in late 2020 or early 2021.

Author: Rare Daily Staff

Stay Connected

Sign up for updates straight to your inbox.