The US Food and Drug Administration announced today that it has granted marketing authorisation to the first-ever gene replacement therapy treatment for SMA. The intravenous formulation Zolgensma® is now authorised in the United States to treat spinal muscular atrophy in children under 24 months. The approval scope includes all children diagnosed with SMA irrespective of body weight, SMA type and SMN2 copy number; it also includes presymptomatic children.
This is the day that the entire SMA community has awaited for years. A second drug to treat SMA is there, and it is – gene therapy!
Gene therapy in SMA is based on an brilliantly straighforward yet extremely difficult to achieve method. The active component of Zolgensma contains billions of viruses that have been emptied from their own DNA and instead loaded with the DNA sequence of the SMN1 gene (technically known as “transgene”). SMN1 is the gene that’s missing in people with SMA. When the modified viruses are injected into the person with SMA, they quickly “infect” his or her motor neurons and other body cells and release the SMN1 transgene into cell nuclei. The SMN1 transgene then picks up the work there and starts producing the SMN protein as if the person did not have SMA.
Zolgensma is a one-off treatment – given that motor neuron cells don’t divide, a single intravenous injection of gene therapy is expected to last for life.
Brilliant, isn’t it? Now this incredible technology is getting to the clinic, hopefully offering us the most powerful SMA treatment to-date.
The work on gene therapy for SMA has a long history. Everything started in the early 2000s in Paris where Dr Martine Barkats, funded by the French patient and research organisation AFM Telethon, successfully treated SMA mice with an AAV9 viral vector. Soon her success was replicated by Dr Brian Kaspar in the US. Understanding the significance of the discovery, Dr Kaspar went on to study the virus and soon was able to treat SMA mice and even SMA pigs that he developed for the purpose. Seeing his successes and the promise the treatment had for people with SMA, the US SMA community offered to fund his work.
In 2014, dr Kaspar registered a company, AveXis, which, over the next years, trialled the new treatment in SMA babies. It has also developed an innovative, unique way to manufacture the virus on a commercial scale. The trial results were breathtaking: children with the most severe SMA went on to sit unsupported, stand and some even walk! In May 2018, AveXis with all its patents and know-how was bought by the Swiss pharmaceutical giant Novartis for a mind-blowing amount of US$ 8.7 billion.
Today, AveXis has registered its first success by putting the first-ever gene therapy product for SMA on the market. Soon, hopefully, Zolgensma will become a standard treatment in SMA.
Even as this is an incredibly promising treatment and even as more than 150 children have already received Zolgensma, it is worth keeping in mind that the drug’s long-term safety and efficacy are not yet fully known. The drug has also other important limitations – please read more on this page.
Zolgensma is also making its way to the UK. AveXis filed for European approval last year and recently commenced NICE procedures. We at TreatSMA have been invited by NICE to present our views on the proposed scope and remit of the possible approval.
While intravenous Zolgensma is intended to treat only young children, older children and adults will possibly be able to use an intrathecal form of the drug which is currently under development. We keep fingers crossed for the success.