James Wymer, MD, FAAN: Risdiplam is an oral molecule that is trying to also increase the amount of SMN2, similarly to what nusinersen is trying to do. It’s a strong advantage that it is an oral medication as opposed to an intrathecal injection. It is still going through some clinical trials and is not FDA approved. We need more data to be certain about its effectiveness, but the initial studies that have come out look very promising. This may be an alternative medication that may work better for some patients with SMA [spinal muscular atrophy]. Being administered orally is a huge advantage.
The mechanism of action is to increase the SMN2 protein. It tries to increase functional protein and transcription of the gene. I’m not sure the exact mechanism is well characterized. It has a similar mechanism to others. That is, to increase the SMN2 so that we can compensate for the loss of the SMN1.
The SUNFISH trial is a later-onset SMA trial. The subjects who were enrolled were between the ages of 2 and 25 years. They were looking for types 2 and 3, not the type 1 disease. Again, they were looking at motor functional scales. They use something called the Motor Functional Measure, on which a 3-point difference was felt to be clinically meaningful.
They had parts 1 and 2. Part 1 has since been released. That showed a clinically meaningful response that was statistically significant in patients who were on the medication. Part 2 is currently under way as a confirmatory study.
Tim Hagenacker, MD: The JEWELFISH study was mainly focused on safety aspects. It included patients who had prior treatment with another SMN2-dependent drug, like nusinersen. Patients were then switched over to risdiplam. There were no new safety signals. We think that risdiplam has a good safety profile. There were no drug-related adverse events that led to withdrawal of the study drug. We don’t think prior treatment with nusinersen interferes with switching patients over to risdiplam.
James Wymer, MD, FAAN: The data so far are saying that the medication has real potential. It needs to go through complete review. It needs to get all the FDA approvals for us to feel comfortable prescribing it. But we have a lot of evidence coming through with this. As clinicians who treat SMA, this presents another potential medication that will hopefully be coming onto the market so that we’ll have multiple ways to treat this disease.
Because of medications like this, SMA has become something where we can personalize the medication. We can decide which of these is going to be the best, and then in combination with the right multidisciplinary care, develop the right exercises. We end up developing an individualized care program that’s specific to each person with SMA.
Tim Hagenacker, MD: Risdiplam is another important drug we need for the treatment of adult SMA because we have patients that get even worse. Also, they were treated with nusinersen, and we have to deal, as I already mentioned, with radiation exposure. We have patients on long-term nusinersen and with every injection, they have increasing radiation exposure. For these patients, and also patients who have severe problems with a neuromyopathic scoliosis and cannot get on treatment, risdiplam is a good option.