Spinal Muscular Atrophy (SMA) Research update and treatment – AUSTRALIA

A research update by Prof. Monique Ryan Director, Department of Neurology
Group Leader, Murdoch Children’s Research Institute,  Royal Children’s Hospital

There has been a lot of activity in the clinical trial space for SMA in the last two years.

Two hospitals in Australia- the The Royal Children’s Hospital and Sydney Children’s Hospital- have been trial sites for the Nusinersen trials, run by Biogen.

The Lady Cilento Children’s Hospital was also a potential trial site for one of these studies but did not enrol a patient.

Nusinersen is an antisense oligonucleotide, or a short synthetic stretch of nucleic acid, that is designed to specifically bind SMN2 transcripts and “correct” SMN2 gene expression

At RCH, we have had several infants enrolled in several of the Nusinersen trials, one for pre-symptomatic SMA type 1 (a trial called NURTURE) and one for SMA type 1 (a trial called ENDEAR, with roll over after 12 months into an open-label trial called SHINE).

In the US and Europe there was another trial- in SMA 2 patients- called CHERISH, which no Australasian sites were involved with.

The SHINE and CHERISH trials have now been stopped because their interim (half-way) analysis showed that the drug was effective in meeting the studies’ primary endpoints (motor development).

RCH, SCH and LCCH have now been invited to register as sites for Biogen’s Extended Access Program (EAP) for SMA type 1 and are in the process of doing so. Other Australian sites may also potentially enrol in this EAP in the forthcoming months.

At RCH, this means we have had to submit detailed applications to the hospital’s Research Ethics Committee and Drug Usage Committee. We have done this and are waiting to hear back from our HREC and DUC. This process takes quite some time. Because Nusinersen is not a licensed drug anywhere in the world yet, and it is undergoing regulatory drug approval processes all over the world, the ethics committee has to be comfortable that it is likely to be safe in this patient population.

The company that owns the drug has not yet been able to release a whole lot of information about the results of the trials, given that some patients have not yet rolled over onto open-label treatment and they have a lot of data to go through.

We don’t yet know when we might be able to set up an EAP of SMA type 2 or who might qualify for treatment under this EAP. We hope to have that information early in 2017.

Nusinersen is given by an intrathecal injection into the spinal fluid via a lumbar puncture.

Children receive an initial series of three injections over 6 weeks then a top-up treatment every four months.

Most children will need to have the procedure done under anaesthetic.

We are in discussion with the RCH anaesthetics team as to how that will be done.

Once we have approval to go ahead with the EAP we plan to talk to the families of all the children we know of who are potentially eligible. This will involve a detailed discussion of the risk/ benefits of the EAP for their child.

We can’t really engage in those discussions yet until we know exactly when the EAP can start and how it will work.

Those risks/ benefits of the EAP might be dependent on the child’s lung function, etc, so that discussion has to be done on a case by case basis once we have permission to proceed.

We are aware of all the children followed at RCH who might be suitable and plan to contact their families as soon as we have the go-ahead to proceed with the EAP.

If there are other families in the community with children with SMA of whom we are unaware we would be happy for them to make contact with us: families can contact Daniella Villano, MDA Neuromuscular Nurse Coordinator (Daniella.villano@rch.org.au ) or Monique Ryan (Monique.ryan@rch.org.au)