Understanding the Newest Therapeutic Advances in Neuromuscular Diseases

Jinsy Andrews, MD, MSc

Therapeutic development has been advancing and increasing rapidly in the field of neuromuscular disease, with a swath of novel approaches making it to market for spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), and Duchenne muscular dystrophy, among others. These advances have included gene-mediated treatments, ushering in not only an era of advancement but one of genetic medicine.

This has presented unique challenges for both physicians and patients, despite the welcomed progress. Determining the proper patient selection for therapies and collecting long-term safety data have proven difficult to this point. Conducting and improving clinical trials has also been challenging for many patient populations with rare or ultra-rare diseases, as well.

At the 2022 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, March 13-16, in Nashville, Tennessee, a session was held that featured a number of expert clinicians discussing treatment selection and management for these disorders. Jinsy Andrews, MD, MSc, FAAN, who herself sees many patients with ALS, was among those clinicians in the session.

Andrews, the director of neuromuscular clinical trials at Columbia University Irving Medical Center, highlighted some of the difficulties in determining who might benefit best from these treatments, and the collection of real-world evidence and data to help inform patients and providers about the use of these therapies in conversation with NeurologyLive^® at MDA 2022.

NeurologyLive^®: When we're talking about complicated and complex diseases, what are some of the challenges that are currently being faced by physicians?

Jinsy Andrews, MD, MSc, FAAN: I think the toughest challenge when we're dealing, especially with chronic neuromuscular diseases, in particular, things like ALS, myasthenia gravis, Duchenne muscular dystrophy, and spinal muscular atrophy, there are multiple clinical trials and multiple FDA-approved therapies, all occurring very rapidly. The first challenge is trying to stay informed about those therapies. That is number one. The second is understanding when to use them, and in which types of patients. So that's a second challenge. The third—which is a much more difficult challenge—as a physician and as a health care provider, many of these things have come on to market really in the last 2, 3, or 4 years at best. And so, when a person living with that disease comes to talk to you about a particular therapy that's brand new, they see the press releases and they see the news outlets covering it. They ask, “Well, what should I expect?” and clinical trials will give us that information about the safety and tolerability within that observation period, which is a limited time—it's not lifetime of somebody—and it will give us the efficacy information. But there will still be things we don't know about a particular drug that gets approved.

In SMA, we have nusinersen and we've got onasemnogene, and those are fairly new. What to expect in terms of safety long-term with chronic dosing, and there are still things that we may not expect. That uncertainty is something I think is new for healthcare providers in this particular specialty.

How might this challenge be addressed and what role can databases such as MOVR play?

Asking about how to collect data in a structured fashion after a drug is approved is a big question in neuromuscular diseases. I definitely face that with ALS, especially because our one recently approved therapy and others that are potentially under review will require additional data for us to understand who would benefit the best from those therapies. It's not just about databases and natural histories, but also about how to use real-world evidence, and how can we get it in a way that we could use it in the regulatory evaluation of a drug? Or, alternatively, how can we use it in a way that could inform practitioners or people living with that particular disease, in terms of what to expect? Or maybe that which population may best respond to that particular therapy as we try to kind of pressure the approval systems and testing and try to be more efficient?

We might not have all the answers when something finally comes to market. But how do we answer that? It's those databases like MOVR, from the Muscular Dystrophy Association, but also real-world evidence, pragmatic trials, doing postmarketing phase 4 trials in a way that people would participate even though a drug is approved. That takes some innovation and trial design and actually partnering with the patient community, but also with the advocacy organizations and the scientists together. Everyone has to be in on that conversation.

How important it is to have the patient voice included in those conversations?

I think it's very important in every disease that when you do drug development or when you talk about newly marketed products for a particular disease. It's not just for neuromuscular disease. It's important to get the patient's perspective and the patient's journey because as clinicians, and as scientists, we think about it differently. We'll think: what's the mechanism of action for that drug, and is it appropriate and safe for my patient, and how do we get access to that drug to the prescription? And we’ll think: what type of pharmacy do we get it from and how do we get it covered?

But then there are aspects about it that a person living with that disease can only provide. What is their financial or economic burden? How does it affect them if they have to come into hospital for the administration of that therapy? How does it affect their family? Is it impacting their family's ability to work, or the maybe a child's ability to attend school? Those kinds of factors are not necessarily very conspicuous, but really important and affect quality of life. We always talk about adverse effects as risks, and even financial risks. But these are other things that should be taken into consideration when you're thinking about different therapies for a particular disease.

For more coverage of MDA 2022, click here.