SMA Newsroom

This is the second drug developed to treat this severe neuromuscular disorder to receive approval in the European Union.

Onasemnogene abeparvovec, marketed as Zolgensma®, is authorised for use in treating patients with 5q spinal muscular atrophy and a body weight of up to 21 kilograms according to the approved dosing guidance, with a bi-allelic mutation in the SMN1 gene and either:

• a clinical diagnosis of SMA type 1, or
• two or three copies of the SMN2 gene, irrespective of the disease type

The marketing authorisation is valid across the European Union (including the United Kingdom) as well as in Norway and Iceland.

SMA Europe is thrilled that a second medication that addresses the causes of this life-limiting disease has moved closer to patients and welcomes the broad indication of this breakthrough therapy.

The approval is a culmination of efforts that have been invested over many years into the development of this innovative, ground-breaking treatment. The global SMA patient community has played an important role, funding much of the preclinical research which led to the discovery and made the development of this therapy possible, as well as providing support to ensuing clinical studies.

SMA Europe would like to draw particular attention to Martine Barkats’s pioneering work on scAAV9-mediated gene delivery to treat spinal muscular atrophy at Généthon, a biotechnology institute funded by one of SMA Europe’s founding members, AFM Téléthon. SMA Europe is proud to have awarded Dr. Barkats funding for this research.

The marketing authorisation in the European Union includes a requirement to collect additional data on the drug’s safety and efficacy. SMA Europe urges Avexis to work closely with the European clinical and patient community to ensure that the future full marketing authorisation is not based on disease types or SMN2 gene copy numbers.

A conditional marketing authorisation may also pose a challenge to accessing Zolgensma as a reimbursed therapy in individual countries with different regulatory systems. SMA Europe calls upon the manufacturer and national health authorities to work jointly on making this breakthrough drug available to the wide population of patients, taking into consideration both the high unmet medical need in treating spinal muscular atrophy and the long-term sustainability of taxpayer-funded healthcare systems on our continent.

“It is with great excitement that SMA Europe received the news of the approval by the European Commission, of a gene therapy for treating a part of our community.  Many hopes have been put into this much awaited therapy. It will be now to all stakeholders involved to ensure that treating doctors, together with parents, can have the best therapeutic option based on the benefit that each of them can provide to each individual. Gathering more data on how Zolgensma impacts the lives of patients will be extremely important to better understand the potential of this new therapy on improving lives of those living with SMA”

Mencía de Lemus, President of SMA Europe

As a patient organisation we, at SMA Europe, believe that it is critical that each person with SMA has timely and sustainable access to safe and effective treatment options. We continue to work closely with healthcare professionals, public authorities and the pharmaceutical industry, to ensure that people affected by spinal muscular atrophy have access to all the therapeutic options they could benefit from.

 

Frequently asked questions

• What is the indication and where can we find any important safety information for Zolgensma?
  • Zolgensma is a proprietary gene therapy that provides a functional copy of the human SMN gene to halt disease progression through sustained SMN protein expression. It is administered as a single, one-time IV infusion designed to provide long-term benefit.
  • A functional copy of the human SMN gene is an adeno-associated virus (AAV) serotype 9, AAV9, which is able to cross the blood-brain barrier to the patient’s neurons without modifying their existing DNA.
  • The most frequent adverse reactions (incidence ≥ 5%) observed in the 4 studies (N=44) are elevated aminotransferases 12 (27.3%) patients and vomiting 3 (6.8%) patients.
  • The final label and safety information will be distributed by the European Commission in the coming days.
• How many patients have been treated with Zolgensma worldwide?
  • Over 500 patients have been treated with Zolgensma, including in clinical trials, commercially and through the Managed Access Program in the U.S.
• Who can receive Zolgensma in Europe?
  • The EC granted conditional approval for Zolgensma for the treatment of patients with 5q SMA with a bi-allelic mutation in the SMN1 gene and a clinical diagnosis of SMA Type 1; or for patients with 5q SMA with a bi-allelic mutation in the SMN1 gene and up to three copies of the SMN2 gene. The approval covers babies and young children with SMA up to 21 kg according to the approved dosing guidance.
    • According to Pediatric Neuromuscular Clinical Research (PNCR) natural history study of SMA, almost all patients under the age of five years of age will be under 21 kg with some patients at 6, 7 or 8 weighing below 21 kg¹
    • Warnings and restrictions in the label note that there is limited experience in patients 2 years of age and older or with a body weight above 13.5 kg and that the safety and efficacy of Zolgensma in these patients have not been established.
  • Ultimately, the decision to treat a child with Zolgensma should be discussed with your treating physician to determine the best treatment pathway for each specific case of SMA.
• Why can’t patients with more than three copies of the SMN2 gene receive Zolgensma?
  • The EC approval was based on comprehensive data from four clinical trials including patients with one, two or three copies of the SMN2 gene which ultimately determined the indication approved in Europe.
    • The approval was based on 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 <6 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, a milestone never achieved in untreated Type 1 patient ²
  • 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 (<6 weeks at age 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 patients²
• Is Zolgensma safe? What are the side effects?
  • The most commonly observed side effects after treatment were elevated liver enzymes and vomiting.
  • Acute serious liver injury and elevated aminotransferases can occur. Patients with pre-existing liver impairment may be at higher risk. Prior to infusion, physicians should assess liver function of all patients by clinical examination and laboratory testing. And, they should administer systemic corticosteroid to all patients before and after Zolgensma infusion, and then continue to monitor liver function for at least 3 months after infusion²
  • There is limited experience in patients 2 years of age and older or with body weight above 13.5 kg. The safety and efficacy of Zolgensma in these patients have not been established.
• Why was Zolgensma granted a conditional marketing authorisation by the EC?
  • The EC granted conditional approval for Zolgensma for the treatment of patients with 5q spinal muscular atrophy (SMA) with a bi-allelic mutation in the SMN1 gene and a clinical diagnosis of SMA Type 1; or for patients with 5q SMA with a bi-allelic mutation in the SMN1 gene and up to three copies of the SMN2 gene.
  • A conditional marketing authorisation is granted in the interest of public health for medicines where the benefit of immediate availability outweighs the risk for less comprehensive data than normally required, based on the scope and criteria defined in legislation and guidelines
    • Post-approval, we will closely monitor for any reports of related safety events in patients and encourage enrolment in the RESTORE, a global registry designed to track the effectiveness of treatments, long-term safety and overall survival global registry.
    • Conditional marketing authorisations are valid for one year and can be renewed annually.
  • Once AveXis collects the necessary data to submit to the EMA, the marketing authorisation may be converted into a standard marketing authorisation (not subject to specific obligations).

References

¹PNCR, Pediatric Neuromuscular Clinical Research. PNCR Database: Weights (kg) by Patient Ages (Months) for SMA Types I, II, and III All Visits. Accessed March 13, 2020. WHO, World Health Organization. Growth reference 5-19 years. Weight-for-age (5-10 years). Accessed March 29, 20.

²STR1VE-US, START and SPR1NT clinical data on file.