Current Series: Advances in the Treatment of Spinal Muscular Atrophy

Crystal Proud, MD: I'd like to shift gears now and review some of the pharmacologic management that we have available: approved medications and those in development.  
 
We are incredibly fortunate to now have treatment opportunities for our patients with spinal muscular atrophy [SMA]. Most recently, onasemnogene abeparvovec-xioi, known as Zolgensma, was approved by the FDA in May 2019. This is a gene transfer therapy whereby an SMN1 transgene is packaged in a viral vector, in this case, adeno-associated virus type 9. It's administered once via an intravenous infusion. The mechanism of action is such that the SMN1 transgene begins producing SMN protein and this, in turn, supports the health of the motor nerves and efforts to maintain the strength of the patient. 
 
It is indicated for patients under the age of 2 years with SMA. In 2018, there was a release of the results of the phase 1 START trial, reporting that all 15 patients administered AVXS-101, now onasemnogene abeparvovec, were alive and without the need for permanent ventilation at 24 months. Eleven out of 12 patients who received the currently FDA approved dose demonstrated the ability to sit unassisted for greater than or equal to 5 seconds. John, can you discuss the impact that this trial, this medication has had on the optimism that we experience for our patients with SMA, as this represented the first neuromuscular gene therapy treatment? 
 
John Brandsema, MD: The START trial was a landmark moment in neuromuscular history, certainly. It has been published in the New England Journal of Medicine, so most are quite familiar with the results if they’ve looked them over, but with the caveats that this was open label, it was single center. Essentially, what we're seeing here is that patients who are symptomatic with the most severe form of SMA, infantile onset disease, are achieving motor milestones.  
 
This is something that, as a neuromuscular specialist, is a celebration when we look at these data, but for families, there are real practical things that are happening in the lives of these children that are changing the experience of the disease entirely. We've had data releases now of long-term follow-up from this cohort of 4 years, where there is continued gain of some of the milestones in some of the patients, and no patient has lost a milestone that was previously acquired.  
 
We're seeing durability now in the data cuts from this cohort, and the other piece is that, for something that has a lot of novelty in terms of an approach, it does tend to be well-tolerated for the most part. Now, we do have to be careful to acknowledge that there are issues with liver injury and transaminase elevation in some of the patients that required longer courses of steroid treatment, and the post-viral syndrome that is seen sometimes with flu-like symptoms. Vomiting, fever can sometimes be an issue, especially in older patients who are treated with this IV [intravenous] form. The efficacy that we’re seeing from the data is highly encouraging for the community in terms of this being a one-time intervention that makes a profound impact on the experience of the disease. 
 
Crystal Proud, MD: Thank you for summarizing that.