European Commission Grants Conditional Approval to Zolgensma for Treating SMA

The European Commission (EC) has granted conditional approval to Zolgensma (onasemnogene abeparvovec) for treating patients with spinal muscular atrophy (SMA) and a clinical diagnosis of type 1 SMA, or for those with up to three copies of the SMN2 gene.

The approval will cover infants and young children with SMA who weigh up to 21 kilograms (about 46 pounds), according to the therapy’s approved dosing guidance.

Also, AveXis, the therapy’s developer that is now part of Novartis, has activated its “Day One” access program that will allow patients to have rapid access to the medication. Immediate access to Zolgensma is already in place in France via the ATU (compassionate use) framework , and is expected soon in Germany.

The “Day One” program also will allow access to RESTORE, a global registry of patients who have been diagnosed with SMA to assess outcomes following SMA treatment, including its effectiveness and long-term safety, to document patient survival, and collect information on healthcare resource use, caregiver burden, and quality of life.

In the meantime, AveXis is in discussions with other EU governments and reimbursement agencies to reach an agreement on the terms of the program that will allow patients in other EU countries to benefit from immediate access to Zolgensma.

“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,” Dave Lennon, president of AveXis, said in a press release.

“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. Additionally, we have met with more than 100 stakeholder organizations across Europe to discuss our ‘Day One’ access program to enable rapid access with customizable options designed to work within local pricing and reimbursement frameworks,” Lennon said.

Zolgensma, formerly known as AVXS-101, is a one-time gene therapy that has been developed to treat all types of SMA. It was approved by the U.S. Food and Drug Administration (FDA) in 2019 as a one-time intravenous (into-the-vein) infusion treatment for newborns and toddlers up to age 2, and more recently in Japan for the same indication.

As in other countries, the EC’s decision to approve Zolgensma, which came shortly after the EMA’s Committee for Medicinal Products for Human Use (CHMP) recommended its conditional approval in March, was based on data from two completed trials: the Phase 3 STR1VE-US (NCT03306277) and the Phase 1 START (NCT02122952).

Both studies evaluated the safety and effectiveness of a single intravenous infusion of Zolgensma in symptomatic infants with SMA type 1 younger than 6 months, who had one or two copies of the SMN2 gene.

SMN2 is a gene similar to SMN1 — the gene that is faulty in SMA patients — that normally remains fully functional in patients, allowing for the production of a shorter and less stable SMN protein. A higher number of SMN2 copies is associated with lower disease severity.

Treatment also led to sustained improvements in infants’ ability to achieve several developmental milestones, including being able to sit independently, crawl, and walk unaided, which were never attained in untreated babies with type 1 SMA.

“The results we have seen for Zolgensma to date from the STR1VE clinical trial show an impressive survival rate at the conclusion of the study, with the majority of patients achieving functional milestones, like sitting without support, that wouldn’t have been reached in untreated infants,” said Eugenio Mercuri, MD, PhD, professor of pediatric neurology at the Catholic University in Rome, Italy.

The approval also was supported by interim data from the ongoing Phase 3 SPR1NT clinical trial (NCT03505099), which is evaluating the safety and effectiveness of Zolgensma in pre-symptomatic babies (less than 6 weeks old) with SMA carrying two or three copies of the SMN2 gene.

Interim findings from SPR1NT showed the medication led to the rapid achievement of several key developmental milestones in an age-appropriate manner, reinforcing the importance of early treatment initiation in SMA.

The most commonly observed side effects of Zolgensma seen across different studies included high levels of liver enzymes (indicative of liver damage and inflammation) and vomiting.

For this reason, it is recommended that physicians perform several lab tests to evaluate liver function before administering the medication to children. Administration of corticosteroids before and after treatment also is recommended, along with close liver function monitoring for a minimum of three months following dosing.

The safety and effectiveness of Zolgensma in children 2 and older, or weighing more than 13.5 kg (about 30 pounds), have not been established yet due to the limited number of cases analyzed so far.

AveXis has entered into multiple license agreements with several biopharmaceutical companies focused on the development of gene therapies, including, REGENXBIO, Généthon, and AskBio, to continue developing and expanding its gene therapy products specifically intended to treat SMA.