Challenges and Considerations in Treatment of Adult Spinal Muscular Atrophy - Episode 8

Utilizing Real-World Data to Drive Evidence-Based SMA Treatment

John Brandsema, MD: We’re fortunate as an SMA [spinal muscular atrophy] community. This is a rare disease, and there are very passionate but also very specialized people who are taking care of it. In terms of people who are truly focused on SMA and have it as their primary focus of their practice, the community is small around the world. We have international care consensus guidelines for this disease, but there’s not a version that includes the new therapies available. This is being worked on, and it should be available soon.

In terms of the targeted treatments that we have to offer, all of them have been studied in research trials, but the challenge is that the research trial is set up intentionally to be able to detect a therapeutic response with the best possible benefit of the investment of doing the trial in the first place. There is a subpopulation chosen for participation in the research that has the potential for maximal benefit to be able to see that benefit. All these trials have strict inclusion-exclusion criteria that kept the patients relatively pure in terms of only being affected by SMA and no other medical concerns. Their SMA-associated medical concerns were at a point where they were not end stage in terms of needing constant respiratory support, having full nutrition by tube feeding, or being unable to achieve a certain score on our functional scales in terms of a floor effect.

When we bring these therapies into the clinic, the challenge we have sitting with the patient in front of us is this: It is probably the least common situation that they’re going to be exactly like the research trial data. Most likely, they have other things going on, and they’re in a different stage of their disease from the people who were studying the research. This is particularly true with adults living with SMA because none of the research trials has included older adults. We now have 1 trial, the SUNFISH study from Roche, that at least enrolled patients up to 25 years of age. There are some adult data associated with sitters with SMA or walkers with SMA treated with risdiplam.

When we start looking at bringing these therapies into the clinic, we have to think about the patient who is sitting in front of us and whether they’re like the patients who were studied in the research trials or whether they’re having different experiences with their SMA related to other medical comorbidities or where they’re at in their experience of SMA-related symptoms and morbidity.

Real-world data become critical in this space because we need to understand how this impacts the patient’s everyday life as well as the outcomes, safety, and tolerability in people who have experiences with the disease that are different from those in the research trial. This is particularly true in adults living with SMA.

I am always encouraged when we see real-world data emerging in the literature, and we have had some recent publications in 2020. There was a large German collaborative that published its experience with nusinersen as well as the natural history in SMA. I know that there are multiple initiatives in the United States that have been multicenter collaboratives to try to gain better experience of both cross-sectional and longitudinal data in adult SMA, both the natural history and on treatment, and how we can frame realistic treatment expectations and outcomes for people living with SMA when they’re making decisions between different treatment options and what might be available to them.

It’s an exciting time in SMA because we’re trying to think about the new phenotype that we’ve created through targeted treatment, in which people are having their survival motor neuron protein deficiency corrected through these targeted therapies. They’re having an entirely different experience with the disease from what would have been expected in the natural history.

How do we better think about the different implications of this from an orthopedic perspective and from a pulmonary perspective as well as nutrition-wise, function-wise, and rehabilitation-wise? What do we do with contractures? What do we do with scoliosis? What do we do with hips? What do we do with diet? What do we do with pulmonary support? All of these are open questions that we need to better understand to optimize in people on therapy.

This is going to be a huge area of focus for many years for our international community focused on the treatment of SMA. It’s exciting to be in a space where 3 different approaches have come into the clinic so rapidly for such a rare disease. It’s an exciting time, and all of us are thrilled to be a part of it. We’re looking forward to collaborating more to better understand how to make life for a person with SMA as functional and independent as possible.


Consultant: Alexion, Audentes, AveXis, Biogen, Cytokinetics, Genentech, Momenta, NS Pharma, PTC Therapeutics, Sarepta, Scholar Rock, WaVE
Research support: Alexion, Astellas, AveXis, Biogen, CSL Behring, Cytokinetics, Fibrogen, Genentech, Pfizer, PTC Therapeutics, Sarepta, Summit, WaVE
Speaker: AveXis and Biogen