John Brandsema, MD: Risdiplam works with a similar concept to how nusinersen has already established efficacy. It’s working on that SMN2 gene, but the difference is this is an oral modulator that can be delivered orally to the patient to increase SMN expression through altering SMN2 gene expression.

Risdiplam is a liquid suspension that can be delivered orally or via G-tube [gastrostomy tube] to people living with SMA [spinal muscular atrophy].

That’s one of the differentiating points. So there have been a couple of pivotal trials that have been collecting data, mostly in Europe because nusinersen’s availability in the United States made it difficult to study here at the time that they were trying to look at.

Peter L. Salgo, MD: Was that because nusinersen was efficacious, so it would be unethical necessarily to take them off the drug?

John Brandsema, MD: It was hard because it was available in the clinic.

Peter L. Salgo, MD: Got it.

John Brandsema, MD: To make the decision to commit to a research trial when you had a clinically available option in this country was sometimes challenging to navigate. But there’s a trial in the infantile-onset population and also in patients with type 2 as well. These are called the FIREFISH and SUNFISH trials. Early efficacy data, as well as safety and tolerability data, have been presented at major meetings and, again, look encouraging in terms of both being well tolerated and having efficacy for SMA.

Peter L. Salgo, MD: Tell me about the data. You said there were encouraging data. What do they look like?

John Brandsema, MD: I think the challenge is that the trials are different in terms of the populations that were studied and the outcome measures. Going across different agents is a bit of a leap in terms of trying to directly compare them. I think it’s also too early in the collection of the data to be certain about it, but there are trends in the right direction with this particular approach. I think what we’re all excited about in the community right now is that because we already have 1 approved therapy and potentially 2 more at least on the horizon for SMA, this approach is now in newborn screening in the United States. We have several states that are already screening newborns for this double deletion. What’s important to understand is that’s about 96% of patients with SMA. But those other 5% who have mutations aren’t going to be identified by newborn screening.

Peter L. Salgo, MD: But when you say newborn screening, is this all newborns? Everybody?

John Brandsema, MD: Yes, everybody born is going to be identified if they have that most common double deletion as being genetically affected with SMA at birth and being referred to a neurologist who then has to decide whether they go on intervention at that point.

Peter L. Salgo, MD: How expensive is the screening?

John Brandsema, MD: So that, actually, is relatively feasible because there’s already a genetic screen in place in most states for immune deficiency, SCID [severe combined immunodeficiency].

Peter L. Salgo, MD: Oh, so you just add this.

John Brandsema, MD: You just add that onto the platform. Then, with this relatively 1 in 10,000 incidence, it’s going to be a handful of patients per state who are identified. But they have the potential to then be intervened on before they develop symptoms of their genetic disease.

Peter L. Salgo, MD: Do you ever feel put upon that all this wonderful medical progress is being dumped in your lap to pay for it? You’re almost like the Grinch that stole cures.

Maria Lopes, MD, MS: Oh, I don’t feel that way at all.

Peter L. Salgo, MD: I’m glad.

Maria Lopes, MD, MS: I’m excited for therapies that, hopefully, work, that impact survival and that impact quality of life. Isn’t that what science is supposed to be doing?

Peter L. Salgo, MD: Isn’t that why, when I speak to you both on and off the air, I’ll tell you this is great. Let me speak for everybody and see whether they all agree. What we’re looking for is a team. Nobody wants to bankrupt the nation, but nobody wants to see people die either. It’s tricky, isn’t it?

John Brandsema, MD: Yes.

Peter L. Salgo, MD: Do you feel sympathy for her?

Sika Dunyoh: Absolutely.

Peter L. Salgo, MD: You do?

Sika Dunyoh: I think I said it earlier: I don’t envy her job at all. I understand the position that payers are in. Speaking for the community with rare diseases, we want treatments. We want therapies—successful therapies—for our patients.

Peter L. Salgo, MD: But you want treatments that work.

Sika Dunyoh: We want treatments that work and that are safe—yes, absolutely. Once those arrive, once they come, we don’t want our families to be bankrupt, right? So how do we ensure that they’re covered? That’s kind of out of our hands, and it’s in the payers’ hands. But it is a challenge, and I understand your position.

Maria Lopes, MD, MS: Yeah.

Peter L. Salgo, MD: Let me put it to you this way. It’s a challenge I’m glad you’ve got. It’s good news.

Maria Lopes, MD, MS: Well, with high hope also come high cost but also high expectations, right? The expectation is that these do deliver cures.

Peter L. Salgo, MD: This has been a tremendous discussion. Before we go, I want to let each of you sum up something you think is really important to take away. Why don’t we start at this end of the table.

Sika Dunyoh: Well, I am actually glad that we’re here having this discussion because we are talking about a couple of disease states that actually have therapies, successful ones, and more on the horizon—which is more than can be said for other disease states. I think that there is a lot of hope for families with SMA, and I’m excited about the emerging gene therapies as well. I think gene therapy gives so much promise to so many families—not just with SMA but some of the families with hemophilia, sickle cell anemia. I think there are so many trials out there, and there is so much hope. I think this is a great time for rare diseases. Not only is there more attention being paid to rare diseases, but there are therapies, potentially curative therapies, out there. So this is a great time for us, and I just hope that this is just the beginning of more to come.

Peter L. Salgo, MD: Any pithy last comment?

John Brandsema, MD: I think we have to be careful using the word cure when we’re talking about these types of disorders. My understanding of the data so far from all the approaches that we have is that nobody is completely asymptomatic. I can’t overemphasize how much of a celebration it is to now be in clinic with people living with SMA. We always try to optimize function and had a very positive dynamic in our clinic as much as possible in neuromuscular disorders. But now we’re seeing videos of all the new things that the kids are doing, and they’re so proud to show us new things that they’re able to do on these therapies. But they’re still living with symptoms, and so they still need to have the multidisciplinary care in place and to keep that connection. I hope that we continue to try to come up with the best possible cocktail of different approaches for patients to optimize their function in a way that is practical for us as a society to sustain this, which is, I think, where we can shift gears to the other end.

Peter L. Salgo, MD: You’ve got the last word.

Maria Lopes, MD, MS: I think this has been a great discussion in terms of value. Hopefully, the conversation will continue to evolve so that in the end, these promising therapies really can demonstrate their value in terms of outcomes and improved quality of life.

Peter L. Salgo, MD: I don’t often sum up my feelings at this moment. I will here. I’m excited, and I am proud to be in a profession that has done this for people and is continuing to do this for people—and that includes insurance. Everybody has got a piece of this, and it’s all going the right way. It’s a pleasure and an honor to be at the table with all you guys. It’s wonderful you’ve all been here. On behalf of our panel, I want to thank you for joining us. We hope that you found this Peer Exchange discussion to be useful and informative. I’m Dr Peter Salgo, and I’ll see you next time.