Economic Burden and Challenges of Trial of SMA

Peter L. Salgo, MD: What is the economic burden of SMA [spinal muscular atrophy], if you can, in this country, direct and indirect?

Maria Lopes, MD, MS: I think it largely depends on the type of SMA. We just heard that there are 4 types, and for type 1, unfortunately these children usually don’t live for very long. With nusinersen, these children hopefully are living longer. But we have to think about the cost of the therapy. Is it impaired survival or unimpaired survival? I think gene therapy especially is going to give us tremendous promise, but we probably need registry data that helps us all understand the direct cost impact, as well as indirect cost impact.

Peter L. Salgo, MD: But you know what I hear when I hear we have to collect registry data? You tell me if this has some resonance with your groups. You say, “My kid is sick now, and I hear that there’s something that may benefit my kid now,” and they come back with, “Well, we’re going to collect data, and maybe in 5 years they’ll have enough cases to show this might work.” What’s the response from that side, from the parent’s side?

Sika Dunyoh: Yeah, it’s not a…

Peter L. Salgo, MD: Not a happy moment.

Sika Dunyoh: Welcome message in that moment. Registry and natural history study data are very important long term to be able to do research and develop therapies for disease states. In this particular case with SMA, there is a treatment there that parents want to get their hands on in the moment. With the Orphan Drug Act of 1983, despite its challenges, it has allowed many more therapies to come to market for rare diseases when there wasn’t as much promise prior to that. It’s interesting because 90% to 95% of rare diseases still don’t have a therapy, an FDA-approved therapy. Prior to having a therapy, you’re just desperate for 1. Then when you actually do have 1, you have different challenges, which is the cost and access.

Peter L. Salgo, MD: But she’s going to say you have to modify that sentence. I’m going to speak for you for just a moment if I may. You say when you actually do have 1, and I hear this little voice saying, “Prove it. Prove it!” You prove it; we’ll pay for it. The problem is proving it takes time, right?

John Brandsema, MD: I think it’s not just time, but also these are rare diseases. So it’s logistically difficult to set up some sort of research trial to actually study this in a meaningful way.

Peter L. Salgo, MD: A trial requires numbers.

John Brandsema, MD: Then you need biomarkers that are reliable in terms of the impact of your therapies. In rare diseases, a lot of times, this is highly challenging. If you have a disease like SMA, which is progressing at different rates in different people and affecting different aspects of their function, how do you come up with a 1-size-fits-all trial that is going to measure that effectively across the spectrum? Then what we end up in the clinic having as a concern is that there will be a research trial that has some data associated with it. But it’s in a very targeted population that has been preselected to be a group that is going to show change in the natural history of the disease—within a certain window of time but also a potential response to a therapeutic intervention that is in a very measurable way. But then that gets approved in a different way in terms of the label, and then we’re trying to decide which of our patients actually could benefit from that therapeutic option without actually having any research experience to base that expectation on in some of the groups that are not like the group that was studied. That is a huge challenge.

Peter L. Salgo, MD: That’s a challenge with rare diseases, right?

Maria Lopes, MD, MS: Exactly, and there lies the conundrum because you may have the FDA indication. You may have a very tight clinical trial. Initially, we are going to pay for it, but we’re going to look to the evidence—we’re going to look to the trial design. We also have a challenge, which is the payment methodology.

Peter L. Salgo, MD: What’s that mean?

Maria Lopes, MD, MS: We probably need innovative ways, not just to pay 1 lump sum. Let’s say that’s $4 million for gene therapy. What if it doesn’t work? How do we maintain affordability over not only 1 condition but potentially 40 that may be coming with gene therapies. I completely agree that we need something today or when these therapies come out, but we also need the assurance that these will be the cures that we’re all anticipating.

Peter L. Salgo, MD: But you know what parents are going to say? They’re going to say, “Please, there’s some hope here. There previously wasn’t any hope. I don’t know if it’s going to work, but it’s all I’ve got. I’m begging you, give this to my child, $4 million in a trillion-, zillion-dollar economy? Come on!”

Maria Lopes, MD, MS: In the end, it begs the need for better data and that we have the ability, perhaps, not to just pay based on hope but maybe amortize the payments so that you pay as you go. And if the treatment is working, the payment is there.

Peter L. Salgo, MD: Again, I’ll put 1 more nail in this 1. Hope? I’ve got hope. That’s worth a lot. Pay for hope. Maybe it’s a good idea. If it doesn’t work, we’ll stop. But for now, that’s all these parents have, no?

Maria Lopes, MD, MS: I think it’s hard paying for hope when $4 million could be used for education, for vaccines, and for so many other areas. I think it’s a tough challenge for the United States and our society to be able to draw the line on what do we pay for and what we don’t pay for.

John Brandsema, MD: But we also have to emphasize that doing everything isn’t always the answer for everybody either. Once you give a realistic portrayal of what somebody might be facing in terms of a certain circumstance, they may make the decision not to pursue certain interventions and other things, and that’s still a legitimate choice in our society, an individualized decision.

Peter L. Salgo, MD: So you do occasionally decide not to treat.

John Brandsema, MD: Yes.

Peter L. Salgo, MD: OK, this is not going where we wanted to go. Maybe the best option is nothing.

John Brandsema, MD: Right, and that is an option that’s presented and discussed when people face these kinds of diseases.