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AVXS-101 is the codename of an experimental drug for SMA being developed by a US company Avexis. AVXS-101, officially known as onasemnogene abeparvovec, belongs to the class of gene replacement therapies, or therapies which modify human DNA. AVXS-101 “infects” body cells with a specially crafted virus that carries inside its shell the missing SMN1 sequence (a SMN1 transgene) as payload.

In this way, AVXS-101 attempts to treat the underlying cause of spinal muscular atrophy which is the lack of SMN1 gene.

The virus used in this therapy belongs to the class of viruses called adeno-associated viruses (AAV). It does not cause any disease. Here also, the original DNA of the virus has been replaced with SMN1 sequence.

AAV viruses are called non-integrating viruses. So, while the SMN1 transgene is placed inside the cell nucleus, it remains separate there and does not integrate with the human DNA. The gene correction 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.

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:

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 November 2018, enrolment has been completed.
  • STR1VE EU – a similar trial run in the European Union. As of January 2019, the trial is open in Italy and UK (London and Newcastle). Several more sites are scheduled to be activated in the following months.
  • SPR1NT – an international clinical trial of AVXS-101 administered intravenously to presymptomatic babies younger than 6 weeks. As of March 2019, the trial is open for enrolment in the Australia, Belgium, France, Italy, UK (London) and the US.
  • 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 March 2019, recruitment has been completed and we are awaiting 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 be conducted globally in 2019. As of March 2019 it is still in the planning stage.

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