Highlighting Rare Disease: Spinal Muscular Atrophy (SMA) Management Considerations - Episode 6
Medical experts provide insights on factors impacting SMA treatment strategies.
Julie Parsons, M.D.: There are a couple of situations [in which I’d consider switching therapy for spinal muscular atrophy]. One is when older patients complain of a wearing-off effect, particularly with nusinersen, when they don’t feel as strong weeks or a month prior to having their next intrathecal treatment. They feel as though they’re losing it, and they want to switch to risdiplam to see whether they can get rid of that wearing-off effect. That’s a scenario in which a patient should be able to see if there’s sustained or additional benefit from switching medications.
We’ve also had patients say, “I can’t remember to take something every day. I’m busy. I have a life. I’m working. I’d rather just come in and get the spinal taps. I tried it orally, and I don’t want to do that.” There’s a patient-deciding factor. Certainly, older patients are the principal drivers in terms of switching medications. It takes longer to see a more subtle effect in patients who are switching medications, so we have to be patient when looking at older patients.
Of the younger patients who have had onasemnogene, patients will respond, but it isn’t the robust trajectory that we’d necessarily expect. With our pooled information and data in terms of treating patients and knowing a little more about the expected trajectory in terms of development of motor skills, there are patients who don’t have as robust a response. There are patients I’d [recommend] having an additional treatment with nusinersen or risdiplam.
With onasemnogene, about 60% of the motor neurons are estimated to be transduced. That leaves a population of about 40% of motor neurons that potentially would be able to be boosted or have some benefit by using one of the SMN2-modulating agents, such as nusinersen or risdiplam. If we had the chance to rescue those additional motor neurons in a young child to give them that benefit before they lose the possibility of saving motor neurons, then that’s an important point to consider. There’s an ongoing trial. Hopefully we’ll get some data from this looking at rescuing patients who have been treated with onasemnogene with nusinersen.
There’s also a trial looking at rescuing patients with risdiplam to see whether there might be benefit. As Dr. Brandsema said, in terms of clinical trials, these are small numbers of patients. These are very well-controlled situations. It doesn’t always reflect real-life situations, but we could at least get some data to look at whether it’s safe to use these combinations and whether there’s any benefit.
At our institution, we follow nerve conduction studies. We don’t have great biomarkers. We’re still hoping to have some biomarkers that help us predict who might need an additional therapy. We don’t have those, but we do use these nerve conductions and we look at those at patients prior to treatment and then periodically — every six months or so — to see if we’re making any improvement in nerve conductions. That may, as well, be a partial indicator of whether there’s a decline or complete lack of improvement in nerve conduction. Maybe that would be an indicator that it might be time for treatment. But I don’t think there’s a standard answer of treating and waiting two or three months. It’s more of an individualized, nuanced approach.
Transcript edited for clarity.