ZolgensmaTM / AVXS-101

Last updated 10th June 2019

What Is It?

Pharmaceutical Company AveXis has been leading the development of the gene therapy treatment onasemnogene abeparvovec, trademarked as ZolgensmaTM (previously known as AVXS-101). It uses harmless, genetically-engineered viruses to increase SMN protein levels. A single injection of ZolgensmaTM into the blood is designed to address the genetic root cause of SMA by replacing the faulty or missing SMN1 gene to limit the progression of the condition.

On 24th May 2019, ZolgensmaTM was approved in the USA for the treatment of children with SMA under the age of 2 years and for children who are pre-symptomatic (meaning that, based on their genetics they are very likely to develop SMA). 

AveXis is also conducting clinical trials to see if an intrathecal administration route, which is directly into the fluid bathing the spinal cord and brain, will address the needs of those who have SMA and are older than 2 years. 

Read more about these trials

How Does It Work?

ZolgensmaTM uses harmless, genetically engineered viruses to increase SMN protein levels. Upon injection into the blood (through “intravenous injection”), the viruses are able to travel around the body and get to a variety of different cells to help restore some of the SMN protein that is missing due to the condition.

Viruses are usually combatted by our immune systems. For example, we may suffer from a flu virus, but then our immune system starts to work and we get better after a week or so. What happens after this is that our bodies then produce proteins called antibodies that will very specifically recognise that particular virus in the future and prevent us from getting sick from the same flu virus at a later date. We develop an immunity to that particular flu virus.

The virus used in ZolgensmaTM gene therapy works in just the same way so as soon as it is introduced to a patient, their body starts to produce antibodies. If they have a second injection of the virus, it won’t work as they will have developed an immunity to it /  antibodies will fight against it. This means that only a single injection of the treatment can be effectively used.

The virus that is packaged with the SMN gene to create ZolgensmaTM can be found in the environment; so, some people, including people with SMA, will have a natural immunity to the virus and will therefore not benefit from the Zolgensma therapy.

Any child, young person or adult being considered for a trial or treatment with ZolgensmaTM always has a screening blood test to see if they have this immunity and would therefore not benefit from or be eligible for the treatment.

What Are The Clinical Trials Results For This Intravenous Treatment?

ZolgensmaTM has been and is still being tested in several different clinical trials (e.g. START, STR1VE EU, STR1VE, STRONG and SPR1NT), which have enrolled a variety of patients with SMA Types (1-3). The gene therapy has been consistently shown to be safe and well tolerated by those treated with the viruses.

The latest decision by the FDA in the USA to approve ZolgensmaTM for SMA patients under 2 years of age comes from the ongoing Phase 3 STR1VE trial and Phase 1 START follow-up trial, both of which include infants with SMA Type 1 and test intravenous injections of the drug.

In the START trial, patients treated with ZolgensmaTM have achieved a range of motor milestones never seen in the natural history of the disease without treatment, including sitting, talking and some patients walking, with no reduction of the effect nearly four years after treatment. In the Phase 3 STR1VE trial, ZolgenmsaTM treatment has been confirmed to result in prolonged event-free survival, improvements in muscle function, and achievement of key milestones.

Read further information about the clinical trial results

Access To This Intravenous Treatment In The UK

This treatment is not yet available in the UK.

A very small number of children with SMA Type 1 have accessed this treatment via clinical trials in the UK (at Great Ormond Street Hospital and the John Walton Muscular Dystrophy Research Centre in Newcastle) and are now being followed up. The Clinical Trials are now closed to any new children. 

AveXis has applied to the European Medicines Agency (EMA) for approval for licencing in Europe – we await the outcome. Following an application by AveXis, the National Institute for Health and Care Excellence (NICE) for England is anyway progressing an appraisal of the treatment to see if it will be recommended for provision by NHS England. It has been listed as a Highly Specialised Technology (HST) appraisal under its full name: onasemnogene abeparvovec.

Avexis has not yet made an application to the Scottish Medicines Consortium (SMC).

Wales and Northern Ireland generally follow the advice of NICE.

Read more about the NICE process and what happens in the rest of the UK, here.

For further information about the previous steps there have been towards access, please click here.

What We Are Doing To Progress Access In The UK

SMA UK will be making a submission to NICE by the deadline of 31st July. We will be asking the Community for their views on this treatment and working with the other patient groups. NICE’s first committee meeting to review Avexis’ application and all the submissions will be on 31st October 2019.

In our submission at the scoping stage of this process, we advocated that it be considered as a Highly Specialised Technology (HST). You can read this here. We also attended the scoping meeting to further voice this view.

Other Information about the Pharmaceutical Company leading the development