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AVXS-101, sold under brand name Zolgensma®, is a drug for spinal muscular atrophy developed by a US company AveXis. Officially known as onasemnogene abeparvovec, it belongs to the class of gene therapies, or therapies that modify human DNA. AVXS-101 “infects” body cells with a specially crafted virus that carries the SMN1 sequence (a SMN1 transgene) as payload inside its shell.

In this way, by adding the missing gene, AVXS-101 addresses the root cause of spinal muscular atrophy. Note that it is a treatment, not a cure – even though it allows motor neurons to function, it does not revert muscle atrophy that might have occurred.

The virus used in this therapy belongs to the class of viruses called adeno-associated viruses (AAV) which are common in the environment and do not cause any disease. AAV viruses also are called non-integrating viruses. So, while the SMN1 transgene is placed inside the cell nucleus and gets to work there, it remains separate and does not integrate with the human DNA chain. The genetic modification of the cell does not get passed on to offspring.

Because motor neuron cells do not divide and normally survive throughout the entire human life, it is assumed that a single injection of AVXS-101 will have a lasting therapeutic effect.

AVXS-101 has been approved in the US on 24 May 2019 and is being sold under tradename Zolgensma®.

Methods of administration

AVXS-101 can be administered in a number of ways. Currently, two routes are being studied:

  • Intravenous administration. AVXS-101 is administered using an IV drip over the course of a few minutes. This method causes the virus to distribute throughout the entire body and is suitable only for young babies who do not require very high doses. Intravenous administration was the first method tested, and the published results show that it is a very promising and powerful drug. Based on the results of two clinical trials, Avexis filed for approval of this intravenous treament in the European Union, Japan and the US, and approval is expected by mid-2019. The company also started approval procedures in the UK, and with current timelines approval should come in late 2020. The drug’s proposed trade name will be Zolgensma.
  • Intrathecal administration. In those whose body weight exceeds 8.5 kilograms, AVXS-101 cannot be administered intravenously, as the required amount of virus will be too close to the toxic dose (every virus is eventually a foreign protein). For them, intrathecal administration is being studied – the drug will be administered in the spinal cavity, through lumbar puncture, much like Spinraza. Clinical trials involving this method are currently ongoing and more are planned. No filing date or trade name for this drug have been announced.


The first clinical trial of AVXS-101 started in May 2015 and included 15 babies with type 1 SMA. The first three babies received intravenously a lower dose of the virus; the following 12 received a dose several times higher.

As can be seen on the chart above, the three children on lower dose remained stable since the injection. On the other hand, those who received higher dose witnessed dramatic improvement of muscle function. After 18 months from injection, the strongest two SMA 1 children could walk and run independently and most of the remaining ones were able to sit without support. The video below, published in October 2016, shows the changes after AVXS-101 treatment:


No drug-related serious adverse events have been reported to-date (but see below). Adverse events included elevated transaminases (liver enzymes) that were treated symptomatically.

There have been two deaths of SMA1 children treated with AVXS-101. One was determined to be linked to the natural progression of SMA and thus not connected with the therapy. The cause of the other, more recent death has not been determined; AVXS-101 could not be definitely ruled out (among other factors) as autopsy results are pending.

One important limitation of AVXS-101 is its immunogenicity. Often a prolonged contact with AAV9 virus elicits an immune response – it is usually not noticeable clinically but it results in creation of AAV9 antibodies. This fact makes any redosing of AVXS-101 practically impossible, even if the drug was to lose efficacy over years, as the virus will be instantly neutralised by the body. It also means that people who have previously been in contact with wild-type AAV9 virus might not be given AVXS-101. Around 40% of adults and a small percentage of children naturally have antibodies against AAV9 and cannot receive the treatment.

Clinical trials

The above clinical trial completed in September 2017, following which Avexis went on to test the treatment in other groups of patients:

  • STR1VE – a US trial of AVXS-101 administered intravenously to babies with SMA type 1. As of May 2019, enrolment has been completed.
  • STR1VE EU – a similar trial run in the European Union. As of may 2019, the trial is running in several EU locations, including in London and Newcastle. Recruitment has been completed.
  • SPR1NT – an international clinical trial of AVXS-101 administered intravenously to presymptomatic babies younger than 6 weeks with a varying number of SMN2 copies. As of May 2019, the trial is open for enrolment in the Australia, Belgium, France, Italy, UK (London) and the US but only for children with 2 copies of the SMN2 gene.
  • STRONG – a US-based clinical trial for children with SMA type 2 younger than 6 years in whom AVXS-101 is administered intrathecally. As of May 2019, recruitment has been completed and we are awaiting trial results.
  • REACH – a clinical trial in which AVXS-101 will be administered intrathecally to children and adults with various types of SMA. This trial is planned to start globally in early 2020.

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