FDA Grants Rare Pediatric Disease Designation to DMD Gene Therapy Candidate SGT-003


Solid Biosciences is expecting to provide initial safety data on SGT-003 from the first couple of pediatric patients with Duchenne muscular dystrophy enrolled in the phase 1/2 INSPIRE Duchenne trial in mid-2024.

Bo Cumbo  (Credit: Solid Biosciences)

Bo Cumbo

(Credit: Solid Biosciences)

According to a recent announcement, the FDA has granted rare pediatric disease designation for Solid Biosciences’ next-generation Duchenne muscular dystrophy (DMD) gene therapy candidate SGT-003. The company anticipates initial safety data for the first 3 to 4 patients treated with the therapy in the phase 1/2 INSPIRE Duchenne trial (NCT06138639) mid-year as well as initial expression and functional data from those patients in the fourth quarter of 2024.1

INSPIRE Duchenne is a first-in-human, open-label, multicenter trial aimed to investigate the safety and tolerability of SGT-003 among pediatric patients with DMD at a dose of 1E14vg/kg. The gene therapy candidate will be administered as a 1-time intravenous infusion to patients in 2 cohorts with a minimum of 3 patients each, with the potential for cohort expansion. The first cohort (cohort 1) will assess the therapy in patients with DMD aged between 4 and 6 years, while the second cohort (cohort 2) will evaluate treatment effects in patients with DMD aged between 6 and 8 years.

Top Clinical Takeaways

  • SGT-003 has received rare pediatric disease designation from the FDA, underscoring the importance of new treatments for Duchenne muscular dystrophy (DMD).
  • Initial safety data for SGT-003 from the INSPIRE Duchenne trial is anticipated by mid-2024, with further expression and functional data expected by the fourth quarter.
  • Preclinical studies show SGT-003's proprietary capsid, AAV-SLB101, leads to improved muscle targeting, transgene expression, and safety compared with earlier gene therapy approaches.

“Solid’s receipt of rare pediatric disease designation for SGT-003 highlights the continuing need for transformational treatments for this devastating disease,” Bo Cumbo, president and chief executive officer at Solid Biosciences, said in a statement.1 “The key components of SGT-003 were rationally designed to improve on first generation gene therapies to provide skeletal muscle tropism, enhanced durability, and improved clinical outcomes. With site activation scheduled in April, and patient screening beginning shortly thereafter, we anticipate dosing patients in Q2 of this year.”

READ MORE: FDA Grants Breakthrough Therapy Designation for AOC 1001 in Myotonic Dystrophy Type 1

SGT-003 uses the company’s proprietary AAV-SLB101 capsid to deliver an encoded microdystrophin protein containing the R16 and R17 nNos binding protein domains. Preclinical data of SGT-003 in mouse models of DMD showed rapid transduction, robust microdystrophin expression levels in the heart, quadriceps, and diaphragm by day 4 post-treatment. In nonhuman primates, SGT-003 revealed promising data, including increased biodistribution to cardiac and skeletal muscle, including the diaphragm, compared with first generation microdystrophin AAV9 gene therapies, suggesting increased transgene expression and an enhanced safety profile.2

Gabriel Brooks, MD  (Credit: Solid Biosciences)

Gabriel Brooks, MD

(Credit: Solid Biosciences)

“Preclinical data suggests that SGT-003 has potential to significantly improve on existing treatments for Duchenne by using a muscle tropic proprietary capsid to deliver a DNA sequence encoding a shortened form of the dystrophin protein which, importantly, includes the nNOS binding domain. nNOS is believed to play a crucial role in both muscular function and endurance,” Gabriel Brooks, MD, chief medical officer at Solid Biosciences, said in a statement.1 “We look forward to rapidly bringing SGT-003 to the clinic and hope to all Duchenne patients in need.”

In 2022, the company announced a pause on development for SGT-001, its previous lead candidate for DMD, in favor of SGT-003.3 Prior to the reprioritization, Solid had presented positive 2-year data from the phase 1/2 IGNITE-DMD trial (NCT03368742) at the 2022 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, held March 13-16, in Nashville, Tennessee, assessing SGT-001. These data, which included the first 3 patients treated in the high-dose cohort (2E14vg/kg), were in line with previous data reported from the 12- and 18-month time points.4

The patients showed improvement in motor function, with a mean 16-meter improvement (range, -12 to 39; mean difference from natural history, +100.6) in 6-Minute Walk Test from baseline and a –1.7 change (range, -3 to –1; mean difference from natural history, +4.3) in North Star Ambulatory Assessment from baseline. The participants also displayed improvements compared with natural history controls in pulmonary function, with a mean 9.2% improvement in forced vital capacity (range, -1.4 to 29.0; mean difference from natural history, +19.2) and a 6.5% improvement in peak expiratory flow (range, -5.8 to 14.8; mean difference from natural history, +16.5). Moreover, patient-reported outcomes improved, and the therapy was generally well-tolerated.4

1. Solid Biosciences Receives Rare Pediatric Disease Designation from the FDA for Duchenne Muscular Dystrophy Gene Therapy Candidate SGT-003. News Release. Published April 1, 2024. Accessed May 15, 2024. https://investors.solidbio.com/news-releases/news-release-details/solid-biosciences-receives-rare-pediatric-disease-designation
2. Solid Biosciences Announces IND Clearance by FDA for Duchenne Muscular Dystrophy Gene Therapy Candidate SGT-003. News Release. Published November 14, 2023. Accessed May 15, 2024. https://www.solidbio.com/about/media/press-releases/solid-biosciences-announces-ind-clearance-by-fda-for-duchenne-muscular-dystrophy-gene-therapy-candidate-sgt-003
3. Solid Biosciences provides second quarter 2022 business update and financial results. News release. Solid Biosciences. August 11, 2022. https://www.solidbio.com/about/media/press-releases/solid-biosciences-provides-second-quarter-2022-business-update-and-financial-results
4. Dreghici R, Redican S, Lawrence J, et al. Ignite DMD phase I/II study of SGT-001 microdystrophin gene therapy for DMD: 2-year outcomes update. Presented at MDA Clinical and Scientific Conference; March 13-16. Poster 46.
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