Until 2016 spinal muscular atrophy was a disease to which there was not only no cure but no approved treatment. Since 23 December 2016 (USA) and 30 May 2017 (European Union), there is an effective treatment to SMA: Spinraza®. Additionally, a number of other compounds remains in development.
Spinraza is only one approved medicine for spinal muscular atrophy. It contains nusinersen, an antisense oligonucleotide whose main function is to repair the damaged SMN2 gene. After modification with nusinersen, the SMN2 gene starts producing high amounts of the SMN protein whose deficiency is the root cause of SMA symptoms.
Spinraza did wonders in the many clinical trials that were carried in the last years as well as afterwards in normal therapeutic usage. Not only did it stop the progression of the disease but the majority of children and adults who were treated with the drug regained strength and muscle function.
Spinraza is administered to the spinal cavity via lumbar puncture. It has to be taken every four months, with an exception of the initial phase of treatment when additional three doses have to be taken over the timespan of four weeks. Treatment has to continue for life or until a newer drug becomes available.
Work on Spinraza began in mid-2000 with three grants offered by a US-based patient organisation to researchers. With time the new discovery was spearheaded into an experimental new drug by the company called ISIS Pharmaceuticals (later renamed IONIS Pharmaceuticals) which named it SMNRx. The compound then underwent several clinical trials in USA and Europe (including the UK) where it showed excellent efficacy.
Spinraza was approved for treatment of the entire spectrum of spinal muscular atrophy across the European Union on 1 June 2017. Since then it became a standard treatment in a number of countries. Elsewhere, including in the UK, it is administered as a part of Expanded Access Programmes for SMA 1 while the authorities analyse offering the drug for the patients.
TreatSMA strives to make sure that Spinraza becomes a standard treatment in the UK and that everyone diagnosed with SMA can access it through the NHS.
Experimental medicines in clinical development
Work is progressing on other compounds designed to treat spinal muscular atrophy, some of which are currently in clinical trials. Below is a summary of each compound – click on the names to learn more.
Branaplam, previously known as LMI070, is an oral drug that works in a similar way as Spinraza: it repairs the SMN2 gene so as it starts producing good amounts of the SMN protein. It is being developed by Novartis and as of autumn 2017 is in a Phase-2 trial in a few European countries while further trials are in preparation.
RG7916 is an oral drug with similar properties and mode of action as Branaplam, except that it is taken daily. It is being developed by a consortium consisting of Roche, PTC Therapeutics and SMA Foundation. Currently, pivotal clinical trials of RG7916 have started across the world and are expected to be completed by 2019.
AVXS-101 is a type of gene therapy: a DNA sequence which is injected in the veins or to the spinal cord where it completely repairs the mutated SMN1 gene. The therapy is developed by Avexis and right now it is entering a pivotal clinical trial in USA and Europe.
Olesoxime is an oral drug that aims to protect motor neurons faced with low levels of SMN protein. It was discovered by a French company called Trophos and funded through the French patient organisation AFM. It held promise in a large clinical trial. Currently it is being developed by Roche, although the work recently slowed down.
CK-2127107 is a drug that acts on skeletal muscles, helping them work with reduced neuronal signalling, as is often the case in SMA. The drug is being trialled in the USA.
Off-label uses of approved medicines
Certain approved medicines seem to offer some benefit to those with SMA and are sometimes prescribed by doctors.
Compounds in early development
Several universities and biotechnology centres follow scientific leads on potential new treatments for SMA, some of which hold a promise of a significant advantage over anything in clinical development. The pathway from lab to pharmacy is long and complex and requires sigificant resources, hence SMA communities worldwide fundraise to support scientific efforts. For more information head to the websites of the main funding organisations in the area of SMA: SMA Europe, SMA Trust, AFM, SMA Foundation, and Cure SMA.