NeuroVoices: Aravindhan Veerapandiyan, MD; Gabriel Brooks, MD, on Unpacking the SGT-003 Phase 1/2 Biomarker Data in Duchenne

INSPIRE DUCHENNE (NCT06138639) is an ongoing open-label, first-in-human, phase 1/2 trial assessing a single intravenous infusion of SGT-003 (Solid Biosciences), an investigational gene therapy, in patients with Duchenne muscular dystrophy (DMD). The study is being conducted across 15 clinical sites in the US, Canada, Italy, and the United Kingdom. As of a December 15, 2025, data cutoff, SGT-003 was generally well tolerated among 32 study participants aged 1 to 10 years and weighing up to approximately 40 kg, with nausea, vomiting, and loss of appetite reported as the most frequent treatment-related adverse events.^1,2

Principal investigator Aravindhan Veerapandiyan, MD, recently presented new interim data of the phase 1/2 study of SGT-003 at the 2026 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 9-11, in Orlando, Florida. New findings showed that thrombocytopenia occurred more frequently in early trial participants but decreased following updates to the prophylactic steroid regimen. In addition, muscle biopsies from 10 participants at day 90 and 2 participants at day 360 showed high vector genome copies and microdystrophin expression. Notably, biomarkers for muscle integrity demonstrated consistent improvements at days 90, 180, and 360 post dosing.

In a new iteration of NeuroVoices, lead author of the study Veerapandiyan, pediatric neuromuscular neurologist at Arkansas Children's Hospital, and senior author Gabriel Brooks, MD, chief medical officer at Solid Biosciences, discussed the updated biomarker findings from the INSPIRE DUCHENNE trial. The conversation highlighted biologic activity alongside improvements in muscle injury biomarkers without emerging safety concerns. The duo also underscored a potentially improved safety profile with a shortened glucocorticoid regimen and reduced liver exposure. Beyond biomarkers, both experts emphasized early functional observations, reinforcing the importance of clinically meaningful outcomes for patients.

NeurologyLive: Could you provide an overview of this study update, including the latest biomarker analyses, microdystrophin expression data, and safety findings in boys with DMD?

Aravindhan Veerapandiyan, MD: We presented the up-to-date data on the boys who were in the trial, and mainly on the biomarkers. We looked at the dystrophin expression data on a greater number of boys than the previous update, as well as some of the other biomarkers, including liver function biomarkers and some cardiac biomarkers.

Gabriel Brooks, MD: We’re thrilled with our partnership with Dr. Veerapandiyan and all of the study sites for the INSPIRE study, which is the phase 1/2 study of SGT-003 in boys 0 through less than 12 who are ambulatory. Dr. Veerapandiyan has shown through the study update is the expression, the transduction expression at 90 days and 360 days, of the patients. Forty of whom have been dosed and are contributing to the safety data set.

In addition to the 60% microdystrophin expression we see at 90 days, which is stable out to 360 days, in fact increasing, we see reconstitution of the sarcoglycan complex with almost a 1-to-1 correlation. So really demonstrating the direct activity of this microdystrophin, recapitulating dystrophin activity. So that’s a real biologic correlate that this microdystrophin is really acting like dystrophin, bringing the sarcoglycan complex back together. nNOS as well, coming to the sarcolemma.

We’re seeing an almost 1-to-1 correlation between microdystrophin expression and nNOS coming to the sarcolemma. So again, a biologic correlate of this microdystrophin recapitulating dystrophin function.

Dr. Veerapandiyan and I, we work together on collecting all of the data in terms of the biomarkers of muscle health and reductions in muscle injury. I’d love to pass it to you in terms of your thoughts about the creatine kinase (CK) reduction, aminotransferase (AST), alanine transaminase (ALT), and those markers.

Veerapandiyan: It is good to see the comprehensive biomarker evaluation in the study, which I think is unique for this program, including the robust dystrophin expression at day 90 and also extending up to day 360. More importantly, the embryonic myosin heavy chain, representing muscle health itself. I think that’s something unique as well.

Looking at the other biomarkers too such as AST, ALT, the liver biomarkers, as well as troponi. Again, there are no safety signals from those biomarkers. Also, liver function seems to be staying at normal in these patients they’ve followed up so far. I think it has the potential to be a treatment option for these boys with Duchenne.

Brooks: One of the things that we’re so proud of in our work with the sites is around safety. With this drug, we made a decision to try to shorten the total duration of high-dose glucocorticoids, because we know that that can really be a burden for these boys, having to go 60 days on high-dose glucocorticoids, especially if there’s liver injury and needing more steroids.

We only go 30 days, and because our capsid is liver-detargeted, it targets muscle with a molecular lock and key to make sure that it targets skeletal muscle 5-fold greater than adeno-associated virus serotype 9 (AAV9), and the heart around 20-fold greater than AAV9. With that, it’s about 50% reduced to the liver. We felt that it would be important if we could shorten that length of high-dose glucocorticoids, that would be really important for parents and the kids.

Then also, especially the peri-non-ambulatory boys, the last thing we’d want is for them to gain weight and then go off their feet because they’ve gained a bunch of weight from having all these steroids. So, it’s been really reassuring what I’ve seen in terms of during that taper. I mean, we just really haven’t seen those liver spikes.

Veerapandiyan: I think also, to highlight the other biomarkers, we will talk about CK and even titin levels that actually continue to be in a lower state, even past that immunosuppressive regimen. That’s also notable.

Brooks: Absolutely. It seems to be exactly that, 30 days taper off, and then we just see a durable reduction. I think we’re really being comprehensive and trying to look at CK, lactate dehydrogenase (LDH), AST, ALT. Of course, AST and ALT are coming from the muscle, not the liver, but we’re seeing them durably continue to be lower.

Veerapandiyan: I’m excited to see the biomarker data, and I’m looking forward to seeing how that translates into function.

Brooks: Yeah, indeed. I know you showed us 2 videos during your talk. We’ve been at Solid Biosciences very respectful about the patient data. If a boy is coming into the study, he’s going to Dr. Veerapandiyan, who’s measuring time to rise, North Star Ambulatory Assessment (NSAA), all of those things. But we’re not looking at the data because we want to preserve it. If a boy’s contributing that data, we want to preserve the integrity of that data for our discussion with the FDA.

However, with the Duchenne video assessments, we’re able to look not just at how fast a boy’s time to rise is, but what compensations they’re using when they’re walking up the stairs, getting into a car, things like that. I think that’s really powerful.

Veerapandiyan: Those videos are impressive. I mean, that’s just like wow. You don’t have to look at any of the data that we presented today. Just look at the videos. The difference, the boy getting into the car, which is one of those day-to-day activities, it is important how it influences activities of daily living.

The difference that you see in the stability and the speed this kid has getting into the car, and of course, the last video that I showed where the kid was doing a headstand. I was like, this is a typical Duchenne patient? I think that doesn’t happen in Duchenne. I think that’s impressive.

Brooks: Just as a sponsor, as a drug developer, we look at these dry numbers, speed of time to rise, but I mean, seeing that is seeing joy, right? That’s really something that I feel grateful just to be a part of right now.

Veerapandiyan: One of the things as a clinician, yes, of course, these numbers are important, like NSAA or time to stand not discounting the importance of those but what’s more meaningful is how this translates into a patient’s everyday life.

I think a kid’s joy like, “I can run faster,” “I’m able to ride a bicycle,” or “I’m able to play with my siblings and friends longer.” Those are things I feel are much more important to quality-of-life improvements.

Brooks: One thing that resonates about that video to me is that Solid Biosciences was founded by the Ganots, who have a son with Duchenne. One thing she was telling me about her son was that he would feel embarrassed when he was getting into the car.

Watching that young man, who before really struggled to get into the car, but then just kind of pirouetted and came in. To me, that resonated. That reminded me of when Annie was telling me that, to give him dignity, and that’s huge.

Transcript edited for clarity. Click here for more MDA 2026 coverage.

REFERENCES
1. Veerapandiyan A, Flanigan K, Mercuri EM, et al. Update on the INSPIRE DUCHENNE Phase 1/2 Study of the Next-Generation Microdystrophin Gene Therapy Candidate SGT-003 for Duchenne Muscular Dystrophy. Presented at: MDA Clinical & Scientific Conference; March 8-11, 2026; Orlando, Florida. Abstract 441.
2. Solid Biosciences Provides Interim Positive Clinical Update on Phase 1/2 INSPIRE DUCHENNE Trial. News release. Solid Biosciences. March 11, 2026. Accessed March 24, 2026. https://investors.solidbio.com/news-releases/news-release-details/solid-biosciences-provides-interim-positive-clinical-update