Access to Novel DMD Therapies Remains Challenging Despite Regulatory Approvals

In recent years, the therapeutic landscape for Duchenne muscular dystrophy has changed significantly, with several novel treatments emerging, including gene-targeted therapies. However, access to these novel therapeutics has been a challenge for patients, according to the authors of a recent commentary published in Annals of the Child Neurology Society.¹

The paper, titled “Access to Novel Therapies for Duchenne Muscular Dystrophy—Insights From Expert Treating Physicians,” outlines challenges patients and providers face when attempting to obtain payer approvals for appropriate use of novel therapies for DMD. With the costs of new treatments often high, coverage denials limit access for most patients. Additionally, delays in treatment initiation due to denials or requirements to show failure on certain therapies before starting others can impact outcomes, as even the latest therapies for DMD are not curative but can delay or slow disease progression.

The American Journal of Managed Care^® (AJMC^®) spoke with corresponding author Aravindhan Veerapandiyan, MD, a pediatric neuromuscular specialist at Arkansas Children’s Hospital and an associate professor of pediatrics at University of Arkansas for Medical Sciences, to discuss the current therapy landscape for DMD, barriers to care access, and why starting treatment early is crucial for these patients.

Veerapandiyan serves as the director of the Comprehensive Neuromuscular Programs at Arkansas Children’s Hospital, co-director of the Muscular Dystrophy Association Care Center, and director of the Parent Project Muscular Dystrophy–certified Duchenne Care Center at Arkansas Children’s Hospital.

This transcript has been lightly edited for clarity.

AJMC: Can you speak to the current treatment landscape for DMD and the disease-modifying therapies that have emerged in recent years?

Veerapandiyan: From a therapeutic landscape perspective, we are in a much different place now than even a few years ago, with multiple treatments that have been approved, and also that are in the pipeline, which is great for the Duchenne community. We have the gene therapy that was commercially approved for boys that are 4 years and older with DMD,² and there are multiple other gene therapy programs that are in different phases of development—phases 1, 2, 3, and also some in the preclinical stage.

If you look along the same lines at the genetic-targeted therapies, there are exon-skipping agents that are commercially approved, and there are also a few second-generation exon-skipping agents that are in the pipeline in clinical trials, which is great. And then there are nongenetic targeted therapies such as small molecules. Edgewise [Therapeutics] is looking at a product that prevents contraction-induced injury. And you have givinostat, which is an HDAC [histone deacetylase] inhibitor that was also approved recently.³ And then there's cell therapies like CAP-1002 that's also been in development.

Aravindhan Veerapandiyan, MD, and colleagues called for improved access to novel DMD treatments in a recent commentary. | Image credit: UAMS Health

So, there are a lot of genetic and nongenetic downstream therapies in the pipeline and that are also approved, which is great. But one thing to keep in mind is none of the therapies that we're talking about are a cure for the disease, right? They are not going to stop the progression or reverse the disease process, just slow the disease progression. I think the future is going to be more of a cocktail or a combination therapy, meaning someone gets a gene therapy and then add on with other targeted therapies. I think that cocktail is going to look different for different patients.

And we should not forget about steroids. We have a couple, including prednisone and deflazacort. We also have the more recently approved vamorolone. And we shouldn't be forgetting about adding them as a disease-modifying therapy.

AJMC: What are some barriers patients face in accessing FDA-approved therapies for DMD, and how can these be addressed?

Veerapandiyan: When we talk about the access to therapies, there are several challenges. One of them that people often talk about is the payers—the different policy payers and insurance coverage. That's more common. When we initially had the gene therapy approval for children aged 4 and 5 years, the overall experience wasn't bad with payers. I think it was more of an overall positive experience, although there were some challenges. But with the other exon-skipping agents, also, we had challenges. It’s mainly the policies that the payers develop, especially when a therapy is approved through the accelerated pathway program. Some payers think that in this case, it’s still an investigational product, and they wouldn't cover that. There's quite a bit of variability in the policy itself among payers across the country, and that's a huge challenge—from a payer perspective.

I think there's also a lot to talk about in terms of challenges from the patients’ and families' side. We talk about patients who are well educated, who are motivated, who have the resources, and who have the knowledge about what's happening. They are proactively reaching out to the providers and to the hospitals to get the therapies, right? But there are also families, for example, where I am practicing, that face challenges even with the basic needs in their life; for example, just getting to the routine clinical care visit itself is a challenge. For them, it's more of an access challenge because of their social factors, and not understanding the therapy and the risks. They have other priorities that are more important than just coming in talking about therapies, and that in itself is a challenge.

Also, you may be in a place where you don't have a center or an expert or a specialist who would be willing to prescribe therapy for you, and that's a challenge. Or your center may not be equipped to do some more complex therapies like gene therapy, so that's also a challenge.

AJMC: Why is timely initiation of treatments so crucial for DMD patients, and what strategies can be implemented to ensure early intervention?

Veerapandiyan: Early treatment is better in terms of outcomes, and we know that the muscle damage starts happening around the time of birth—maybe even in utero, because when we check the creatine kinase (CK) levels at birth, they're high already, so we know that muscle damage happened already. I think we just have to intervene as early as possible from a therapy standpoint and from a services standpoint. Early intervention with other therapies, such as physical and occupational therapy, is also critical and can affect the developmental trajectory of these boys.

It's crucial to get that diagnosis early, but we're still facing delays in diagnosis due to lack of awareness among the primary care providers. If you look at MD STARnet data, when they looked at the data in diagnosis many years ago and compared it recently,⁴ there wasn't a change, even after a lot of efforts from the American Academy of Pediatrics and other organizations to improve that. I think that goes back to lack of awareness and the wait-and-watch approach that primary care providers maybe take. It is critical to know, and you can easily do a serum CK level when you when you see any kid with developmental delay that can help you with the diagnosis.

The other initiative that's being advocated for is newborn screening; of course, that is going to help with early diagnosis. Yes, it's going to open up some other challenges in terms of phenotypic and genotype delineation—who's going to be Duchenne phenotype and who's going to be Becker phenotype? There will be challenges, but still it can help you with early diagnosis and maybe early intervention, not only from a therapeutic standpoint, but also from an early intervention with services standpoint.

References

1. Veerapandiyan A, Connolly AM, Mathews KD, et al. Access to novel therapies for Duchenne muscular dystrophy—Insights from expert treating physicians. Ann Child Neurol Soc. Published online June 11, 2024. doi:10.1002/cns3.20076

2. FDA expands approval of gene therapy for patients with Duchenne muscular dystrophy. News release. FDA. June 20, 2024. Accessed August 2, 2024. https://www.fda.gov/news-events/press-announcements/fda-expands-approval-gene-therapy-patients-duchenne-muscular-dystrophy

3. FDA approves nonsteroidal treatment for Duchenne muscular dystrophy. News release. FDA. March 21, 2024. Accessed August 2, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-nonsteroidal-treatment-duchenne-muscular-dystrophy

4. Thomas S, Conway KM, Fapo O, et al. Time to diagnosis of Duchenne muscular dystrophy remains unchanged: Findings from the Muscular Dystrophy Surveillance, Tracking, and Research Network, 2000-2015. Muscle Nerve. 2022;66(2):193-197. doi:10.1002/mus.27532