CHMP Recommends Conditional Approval of Zolgensma for SMA in Europe

The European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP), has recommended conditional approval of Zolgensma (onasemnogene abeparvovec) for the treatment of patients with spinal muscular atrophy (SMA) and a clinical diagnosis of type 1, or for those with SMA carrying up to three copies of the SMN2 “backup” gene.

The European Commission (EC), which typically follows CHMP’s recommendations, is expected to make a decision on potential approval, which will be applicable to all 27 EU country members, along with Iceland, Norway, Liechtenstein, and the U.K., in June.

To provide immediate access to Zolgensma at the time of the European Medicine’ Agency’s potential approval, AveXis is offering an innovative Day One access program to EU governments and reimbursement agencies.

Zolgensma, formerly known as AVXS-101, is a one-time gene therapy originally developed by AveXis, now part of Novartis, to treat all types of SMA. It was approved by the U.S. Food and Drug Administration last year 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.

“Today’s positive CHMP opinion for Zolgensma marks a critical step closer to EC approval and to bringing the only gene therapy for SMA to Europe, helping to address the devastating impact the disease has on patients and their families,” Dave Lennon, president of AveXis, said in a press release.

CHMP’s recommendation was based on data from two completed trials — the Phase 3 STR1VE-US (NCT03306277) and the Phase 1 START (NCT02122952) — that assessed the safety and efficacy of a single intravenous infusion of Zolgensma in symptomatic infants with SMA type 1 under 6 months of age with one or two copies of the SMN2 gene.

SMN2 allows for the production of a shorter and less stable SMN protein; a higher number of copies is associated with lower disease severity.

Findings from these studies showed a single infusion of Zolgensma led to rapid improvements in infants’ motor function, which were, in many cases, already apparent within a month after dosing.

Moreover, treatment also led to sustained improvements in infants’ ability to achieve developmental milestones, including being able to sit independently, which was never attained in untreated babies with type 1 SMA.

Two similar trials, called STR1VE-EU (NCT03461289) and STR1VE-AP (NCT03837184) are currently underway in Europe and Asia, respectively. A long-term extension study of START (NCT03421977) is also underway to evaluate the safety, tolerability, and efficacy of Zolgensma in children originally treated in START.

“In the most severe forms of the disease, children who are not treated are unable to lift their heads, sit, stand, or even swallow, and typically do not survive beyond two years of age unless permanently ventilated,” said Francesco Muntoni, PhD, professor and pediatric neurologist at the Great Ormond Street Hospital for Children in London.

“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 being able to sit without support. And through follow-up on the START trial, an average of 4.5 years later, we can see the long-term potential this significant gene therapy may have for children with this rare disease,” Muntoni added.

In addition to data from STR1VE and START, CHMP’s recommendation was also supported by findings from the ongoing Phase 3 SPR1NT trial (NCT03505099), which is evaluating the safety and efficacy of Zolgensma in presymptomatic babies (younger than 6 weeks old) with SMA carrying two or three copies of the SMN2 gene.

Interim data from SPR1NT showed that a significant proportion of infants treated with Zolgensma achieved milestones, including the ability to sit independently, within the window of normal development. In addition, nearly all children treated so far are still alive, free of ventilatory support, and able to eat without support.

The most commonly observed side effects of treatment seen across different studies include 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.

“Zolgensma provides a transformational new way to treat this rare but debilitating disease — delivering a potentially life-saving medicine with a one-time administered treatment. Given the urgency to treat SMA and the novel nature of gene therapy, we need to be equally innovative in advancing access, so we are offering governments and reimbursement bodies a ‘Day One’ access program to enable rapid access to Zolgensma upon approval,” Lennon said.

In Europe, SMA poses a significant burden to the healthcare system, with cumulative estimated costs ranging from €2.5 to €4 million per child, within the first 10 years alone.

The Day One access program offered by AveXis to EU governments and reimbursement agencies is intended to give patients immediate access to Zolgensma as soon as it is approved in Europe. The program, which can be tailored to suit the needs of each particular country, is designed to ensure that all reimbursement programs are in place and in agreement with negotiated value-based prices by Zolgensma’s potential approval date in June.