Handling Neuromuscular Gene Therapy at Real-World Sites

Natalie Goedeker, CPNP

Since the FDA's approvals of Sarepta Therapeutics’ delandistrogene moxeparvovec-rokl (marketed as Elevidys), an adeno-associated virus (AAV) vector-based gene therapy approved by the FDA for the treatment of Duchenne muscular dystrophy (DMD), and Novartis’ onasemnogene abeparvovec (marketed as Zolgensma), an AAV vector-based gene therapy approved by the FDA for the treatment of spinal muscular atrophy (SMA), clinical treatment centers have been gaining real world experience with these products. As such, an interest in holding a discussion on the experience gained led to a new session entitled "Gene therapy for intermediate/experienced sites" being held at the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific conference, held March 16 to 19, in Dallas, Texas.

Shortly after the conference, CGTLive® spoke with Natalie Goedeker, CPNP, the codirector of pediatric neuromuscular clinical research at Washington University in St. Louis, who chaired the session. Goedeker gave an overview of the key points that came up during the discussion and her view of the big picture takeaways

NeurologyLive: Can you give some background info about your session at MDA 2025?

Natalie Goedeker, CPNP: I chaired a session at the MDA conference this year on gene therapies. The session title was actually "A workshop on gene therapy for moderate to experienced sites", meaning not a brand new site who's not dosed a patient or maybe only dosed a patient or two. The goal was to be an outlet for conversation and communication for sites who've been doing a little bit more gene therapy in the neuromuscular space based on some feedback after last year's conference that there really wasn't that outlet for communication and conversation about how sites maybe do things differently, how they're managing patients, how they're managing safety, how they're managing the logistics. So it was really just a goal of having a conversation.

I chaired the session and had 2 speakers as part of a panel, Dr. Kathy Matthews, MD, FAAN, from University of Iowa, and Dr. Craig McDonald, MD, who's out at UC Davis in California. We all just kind of had a panel discussion and then invited the audience to participate.

What were some of the key things that came up in the discussion?

We used case-based presentations to facilitate conversation. We had cases on both children with SMA who were treated with zolgensma gene therapy and children with DMD who were treated with Elevidys gene therapy, or cases kind of surrounding some of the major issues of treating patients in those 2 buckets.

It had recently been announced that there had been a death post-Elevidys dosing in a teenager and so much of the conversation related to dosing older and heavier patients did sort of reflect on what happened to that young man, and kept that in mind in terms of safety monitoring. For children with SMA, there were some interesting one-off situations that are maybe not one-offs anymore, now that we're doing this more frequently: how to handle a newborn screened child where the family is not bringing their newborn to clinic, and really this is an urgent situation and the child needs to be treated in our minds—you know, we've been caring for these children for years. Other ethical conundrums related to what we would do if a teenage young man with DMD didn't want to pursue gene therapy, but mom and dad did—and so just those sorts of ethical types of conversations, as well as conversations on how different sites are executing the logistics. Sites are not always following exactly the FDA label for lab and safety monitoring. Some sites are doing more intensive monitoring. Some sites are having patients live close to clinic for a certain number of weeks. They're keeping children home from school. And so we just had a conversation on how everybody does things a little bit differently, and the rationale for why. It was really, really a great conversation.

What would you say are the main things you would want the healthcare community to take away from the discussion?

I think the main takeaway would be that there can be some nuance differences based on local practice and local protocol, and that's okay. Not every site has to execute gene therapy administration and follow-up in the exact same way. It still can be done well, with some slight differences between sites.

The other main takeaway is that it really takes a robust team to be able to safely and effectively and efficiently execute giving gene therapy. That was another main topic of conversation. It's not just those of us who are prescribing these medicines who are integral to the team. It's the people who are working on the insurance piece, it's our colleagues in other specialties who help us monitor the patients—our cardiology colleagues, pulmonology—and so it really takes a robust team to do gene therapy well.

What are some of the unanswered questions that still remain in this space?

I think some of the outstanding questions related to gene therapy are related to some of the safety monitoring. In clinical trials, these are rare diseases, and so we are only dosing pretty limited numbers of patients and so it has to be recognized that when these drugs get commercialized, the safety side of it is probably not just going to be reflected in what happened in the clinical trials. There has to be recognition that we need to be vigilant for new adverse events and that it's really a serious thing when you dose a child with gene therapy. We just need to be mindful to not become flippant about it the more and more we dose these patients because new side effects do come up, and I think that was a good takeaway from our conversation.

Is there anything else you want to share?

I think that I really enjoyed the discussion. I enjoyed hearing how Dr. Matthews and Dr. McDonald do things a little bit differently than our practice here in St. Louis. Then I also really enjoyed the conversation from the audience. There was a physician who said, "some of my patients live on the other side of a mountain range and if it snows in the winter and something happens, they can't get to me. And so I have to have them live in a certain distance if I'm going to be safely dosing gene therapy."

Just kind of thinking of those nuances and having conversations about my patients in the Midwest—many of them are rural—they're not financially well-off. It's a real hardship to ask my families to live within an hour or 2 hours of our center and ask them to miss work, and sometimes that would just be a total hindrance to their child getting gene therapy. Just hearing that conversation and having the recognition, again, that everybody does things a little differently, and as long as we are all vigilant in trying to keep our patients safe, that's probably okay.

This transcript has been edited for clarity.

Read more coverage of the 2025 MDA Conference here.

REFERENCE
Gene therapy for intermediate/experienced sites. Presented at: 2025 MDA Conference, March 16-19; Dallas, Texas.