Spinal Muscular Atrophy: Treatments, Early Diagnosis, and Payer Challenges

Gary Owens, MD, president, Gary Owens Associates, describes the current treatment landscape for spinal muscular atrophy and the challenges payers face when covering this patient population.

Welcome back to Pop Health Perspectives, a conversation with the Population Health Learning Network, where we combine expert commentary and exclusive insight into key issues in population health management and more. In this episode, Dr Gary Owens sheds light on spinal muscular atrophy, including payer challenges and current treatments.

I'm Gary Owens. I'm president of a small payer market access consulting organization based in Delaware. My background is one of a primary care physician, but I spent most of my career in the payer world, with over 2 decades in the Blue Cross system and almost another decade working with employers on their benefit programs. I'm still active doing work around payer market access, value propositions, and other things around access.

Thank you, Gary. Can you describe the current treatment landscape for spinal muscular atrophy (SMA)?

I certainly can, and all the treatments for SMA that we've seen in the last few years have been targeted at the more severe forms of the disease. Typically, when we're talking about SMA, even though we know that there are actually 4, even 5 types if you count Type 0, most of the treatment is targeted at the more severe SMA Type 1 or infantile SMA. It's certainly a relentlessly progressive disease leading to disability and death at a fairly young age. And these are patients who have 2 or 3 copies of the SMN2 gene. So they have the severe disease. Type 2 patients, which account for probably only about 20% of the cases and are less severe, still deserve treatment, although a good number of them live well beyond infancy into later adolescence and even young adulthood.

The treatment really has been marked by a number of new treatments. Of course, we have first the disease modifying therapy, nusinersen. Nusinersen is an antisense oligonucleotide that modifies the SMN2 gene splicing and hopefully increases production of that gene. The drug is moderately effective. Its drawback, of course, is that it has to be administered by intrathecal injection on a frequent basis, at least initially with 3 loading doses, and then the fourth one about a month later, and then a maintenance dose every 4 months. So it really means an intrathecal injection on a frequent basis. And of course, the big payer concern is that this drug costs about $125,000 per dose. As you can see, it doesn't take a long time for the cost of this to add up to a 7-figure number.

There's the gene therapy onasemnogene abeparvovec, which is a gene therapy, again tested on patients who had homozygous SMN1 deletions. It was shown to be effective. As you might guess, it's a single one time dose by intravenous infusion. Then the patient needs to be monitored for some of the downstream potential adverse consequences such as liver dysfunction. The estimated cost of this drug used to be one of the most expensive, although it's recently been eclipsed by a new therapy for a blood disorder, was just a bit north of $2.1 million. So again, another 7-figure drug.

Then there's risdiplam. It's a small molecule SMN2 splicing modifier, and the important benefit of it is it's an oral administration. The daily dose, however, is both age and weight dosed, so that as the patient ages and gets older, the dose of the drug goes up. And again, it's a drug that's in multiples of 6-figures for a course of treatment.

All of these have really changed the prognosis for SMA. They've seen children make gains that they maybe otherwise haven't been able to achieve, and they've certainly seen slowing in the progress of deterioration, I guess is the best way to put it. But none of these treatments are a cure for SMA, and they're also phenomenally expensive. So when you tend to look at it on that cost vs benefit, these are fairly high cost treatments, but compared to the alternative, which is typically in Type 1 disease, a relentlessly progressive disease to death at a very young age, they add important pieces to the armamentarium of treating SMA. So payers do manage access, but at the same time are aware that these are much needed therapies.

You touched upon this a bit, but can you discuss the challenges payers face when covering patients with SMA?

I think the challenges that payers face are almost entirely around the cost of treating this and making sure that the appropriate drug is given to the appropriate patients. For instance, for the gene therapy option, this should be reserved for patients who are ages 2 years or younger. I believe that was the FDA approval back when it was approved in 2019. They needed to be under 2 years of age with biallelic mutations in SMN1. So payers want to make sure those are appropriate candidates. Likewise, they're going to manage nusinersen to its FDA approved indication. Another issue payers sometimes run into is, especially for treatments that are given on a maintenance basis, that would be nusinersen and risdiplam, is there a point at which the drug no longer seems to be working and should it be stopped? And they always run into the dilemma of, "Well, what would the progress of this patient or lack thereof looked like or will look like if the drug is no longer given?"

It's what I've often called the Alzheimer's disease effect, where often drugs are continued well beyond their useful period of time, just because we simply don't know or couldn't predict what the progress would be if the drug is no longer there. It's a long way of saying the concern for payers is cost. There's also a cost to the member because many of these, well, they're all in a co-insurance tier, and many families may have significant out of pocket costs. Some or a portion of which may be offset by manufacturer assistance, but this is really a cost vs benefit type of concern for payers.

Thank you. And what are the primary challenges in treating pediatric populations, particularly those with genetic diseases?

I think the big challenge, number one, is getting them in the hands of centers of excellence, people who understand these diseases. SMA is just one of many, many, many genetic diseases. More commonly are things like cystic fibrosis, which is the commonest autosomal recessive disease seen in Caucasians, and there are 30,000 to 40,000 of them in the country. But again, it's getting them into centers of excellence, pediatric centers of excellence, and specialized treaters for this disease. It's making sure that the diagnosis is made properly and confirmed by proper genetic testing. Most payers do support the genetic testing and/or genetic screening because as you probably also know, most states support multiple screens for genetic diseases now done in the newborn screening.

Payers do support NBS—newborn screening, and treatments based on finding these children with these newborn diseases. And a lot of times, finding that early can lead to improved outcomes, even in SMA and cystic fibrosis that I mentioned and some other genetic diseases. So it's really about getting these patients to the right providers so that they can get the specialized and often team care, because these diseases generally take more than just the physician. You need nurse coordinators. You may need physical therapists, social workers, psychologists to help with the dynamics of the disease and even sometimes the family dynamics. It's really about coordinating all this complex care for these children with very complex genetic disorders.

Thank you so much. And is there anything else you would like to add to the conversation today?

I think the one thing is that we do know that for SMA and for many of these other diseases, this is an area of robust research and development, sometimes funded privately by drug manufacturers, but there is also a lot of public funding in this. So I think payers are on the lookout for new treatments and how these new treatments might improve what we have today. I think what we have today, while it's a first step, is by no means going to be the ultimate treatments for these diseases. This is a scenario that payers are going to have to stay on their toes and continue to see what's coming down the pipeline and continuously adjust their management approaches and techniques based on the new developments in the field.

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