Screening and Diagnosis of SMA in Children and Adults

EP: 1.An Overview of the Epidemiology of SMA

EP: 2.Clinical Burden of Spinal Muscular Atrophy

EP: 3.A Multidisciplinary Approach to Diagnosis and Treatment

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EP: 4.Screening and Diagnosis of SMA in Children and Adults

EP: 5.Challenges with Payor Systems for the Diagnosis of SMA

EP: 6.Adapting to Rapid Advancement in Treatments in SMA

EP: 7.New DMTs in SMA: Nusinersen

EP: 8.New DMTs in SMA: Onasemnogene and Risdiplam

EP: 9.Payor Perspective on Coverage Decisions for DMTs in SMA

EP: 10.Shared Decision Making When Selecting a DMT in SMA

EP: 11.Unmet Needs and the Future of Treatment in SMA

Dennis Scanlon, PhD: Let’s move on and talk a little more about specific treatment options. Dr Ciafaloni, we talked about diagnosis, and you gave us a nice general background. We have also talked about the importance of early screening, particularly in infants and young children. Could you talk a little more about specifically newborn screening: what it is, what you are looking for and testing for, how accurate it is, and how actionable it is in terms of making treatment decisions?

Emma Ciafaloni, MD: We are in a mixed model right now in the United States. Because of the newly approved treatment in the past few years, SMA [spinal muscular atrophy] was finally able to be added to the recommended uniform screening panel for newborns. As you know, it takes a lot of background work to make the case that a disease is ready to go on the newborn screening panel. There are many principles that need to be met. As a community, we think that SMA has met all of those, especially with all the data so far in clinical trials indicating that treating as early as possible has a huge impact. The sooner the better. Newborn screening is a reality.

I believe 34 out of the 50 states are actively screening statewide. In the next few years, it’s going to be universal in all 50 states. But right now, we’re in a mixed model. Depending on where you’re born, you might see a neuromuscular expert at 3 to 7 days of age and have a diagnosis and start planning for best care. If you’re born in a state that has not implemented newborn screening, you’re still relying on that clinical diagnosis with the associated delay. It’s a mix, but we’re definitely going in the right direction with newborn screening. Newborn screening right now applies to about 70% of all newborns. We’re going very fast, but as you know, it depends on the individual state policies. Some states just take longer.

Moving forward, this is going to revolutionize the diagnosis, care, and also the phenotype. We talk about types 1 through 4. We talk about SMN2 copy numbers. But right now, if you have a baby who is 3 days old and you have the copy number, you don’t necessarily know their trajectory. You can predict based on the copy number, but you don’t know. Once you treat them very early, we are all learning what the ceiling is. Are we moving from type 1 into type 2 or 3? We’re all learning together. But certainly, their natural history is changing dramatically. There is no question about that.

Newborn screening is interesting because you get a call from the health department very early, 3 to 7 days after the baby is born. After that, time is motor neuron here. You really have to get that village going, call the family, and break this news, which is psychologically shocking. You have a newborn baby, and now you’re telling me I have this genetic disease that might happen sooner or later? And then, on top of that, you have to talk about all these different treatments and which one is best. There is a lot of expertise, genetic counselors, neuromuscular experts, social workers, nurses, and testing that needs to be done. You need to confirm the genetic test. The screening is extremely sensitive and specific, so usually, there are no false negatives in this particular newborn screening. Things move very fast after that. But that first visit is emotionally very tense. And also, because time is so important, you need to get going. It really takes a village for that after newborn screening. This is really going to change the outcome for these patients. It’s a very exciting program.

Dennis Scanlon, PhD: Are there any comments from any of the other panelists on the newborn screening component, including any concerns from an insurance or reimbursement perspective around making sure that happens as promptly as possible?

Mary Schroth, MD, FAAP, FCCP: Let me add that there are 5% of all individuals with SMA who will not be picked up by newborn screening, so continuing to have astute clinicians recognizing the symptoms will continue to be important. It’s a very small percentage, but we need to keep that in mind.

Kevin U. Stephens, Sr., MD, JD: I’d also like to say that it’s very important to move quickly. The sooner the better. The earlier you seek interventions, the better it is for everyone. It’s very important to get the message out that we should do screening, particularly in those who are at the greatest risk.

Maria Lopes, MD, MS: I couldn’t agree more. You’re not going to regain the function you’ve lost. You’re not going to regain the milestones. So certainly, it’s a missed opportunity and important for the remaining states in lobbying to make sure that this gets on the agenda and moved forward. I can only imagine: at day 3 or day 7, the mom’s probably already at home and now receiving this call. The ability to be able to immediately connect to that expertise is very important. Who are they going to call? Are they calling the pediatrician who may not know anything about where to refer and what to do? How do you assist with the connectivity to expertise in the area, facilitate the referral, and even assist the pediatrician? Because again, the sooner the better in terms of how quickly that baby is assessed and the right treatment can be initiated.

Dennis Scanlon, PhD: Dr Ciafaloni, you talked about early detection and diagnosis in the infant and young child population. Could you talk about adults? Earlier, you talked about the 4 types, types 3 and 4 in particular. But shift gears a little bit and talk about detection, screening, and diagnosis in the adult population.

Emma Ciafaloni, MD: I want to make a very important comment that has to do with ethics. Remember that now, with newborn screening, we are leveling the plane for all patients. We have a responsibility, certainly as doctors, but also as a community and society: payers, patient organizations, families, and doctors. You need to level the plane for all babies. We know that health disparities exist even in very common diseases like breast cancer and diabetes. In rare diseases, we have an opportunity here with newborn screening to maximize benefit, outcome, and access to all patients who are eligible for these treatments. I want to put that out on the table because it’s our duty to do it right.

In terms of diagnosis, the newborn screening is going to erase the diagnostic delay for about 95% of patients. But for the type 3, and especially the very rare type 4, it is more difficult. I suspect there are still patients out there, especially adults with SMA, who might be misdiagnosed. When nusinersen was first approved, many patients with SMA, because there was no disease-modifying treatment, were falling through the cracks. They were not necessarily all tapped in at a multidisciplinary clinic, following up every 6 months. When the first drug was approved, we had a resurgence. Our clinic rosters went from maybe 20 or 30 patients to 120 because they started to say, “Now when I go see my neurologist, maybe there is something that can be done for me.” That is phenomenal; it’s a fact. It impacted diagnosis and so forth.

Then, of course, came the awareness that maybe that patient, adult or teenager, with difficulty walking who has no genetic confirmation might now require us to be a little more aggressive. And with free genetic testing, of course, for SMA; right now, there is free, easy, genetic testing that can be done through saliva or blood draw. It’s very easy to confirm the diagnosis. Everybody in the field should be more proactive to screen patients who might have SMA because now they can really make a difference. The field is going in the right direction. Even for the teenagers and adults, we are now, as a community, more aware that we need to do the gene testing at a lower threshold to rule in or rule out SMA.

Transcript edited for clarity.