SGT-001 Shows Efficacy in DMD in 1.5-Year Data


Patient-reported outcomes, 6-minute walk test, and NSAA scores all showed improvements over natural history data.

SGT-001 (Solid Biosciences) continues to show efficacy in treating Duchenne muscular dystrophy (DMD) as seen in positive 1.5-year data from the IGNITE-DMD clinical trial (NCT03368742) presented at the World Muscle Society 2021 Virtual Congress.1

Investigator Vamshi Rao, MD, attending physician, neurology, Lurie Children’s Hospital of Chicago and assistant professor, pediatrics (neurology and epilepsy), Northwestern University Feinberg School of Medicine, presented the data, which include sustained improvements in patient-reported outcomes (PROs) at 1.5 years compared to baseline and natural history data.

“The data presented today demonstrate durable expression and function of microdystrophin protein in biopsy samples collected 12 to 24 months post-dosing of SGT-001,” Rao said in a statement.1 “Additionally, these data provide encouraging evidence of functional benefit at 1.5 years post-treatment compared with natural history data and show meaningful improvement in patient-reported outcomes. Data from additional patients should enhance our understanding of the role that SGT-001 may play in improving outcomes for patients with Duchenne.”

“We continue to believe that SGT-001 has the potential to provide differentiated benefit to patients with Duchenne and are on track to dose additional patients in IGNITE DMD,” Ilan Ganot, chief executive officer, president and co-founder, Solid Biosciences, added to the statement.1

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The updated data presented includes 1.5-year outcomes for patients 4 to 6. These patients all received 2E14 vg/kg of SGT-001, an AAV gene therapy that delivers microdystrophin. SGT-001 has previously received rare pediatric disease designation and fast track designation.

Investigators saw minimal changes in north star ambulatory assessment (NSAA) scores, with an average decrease of 1.7 points (range, –3 to 0) from baseline compared to natural history, which would suggest a 4.5-point decline in NSAA score (mean difference, 2.8 points). Similarly, 6-minute walk test distances increased by a mean of 15.3 meters (range, –17 to 56) from baseline for a mean difference of 78.8 meters from natural history data. Predicted forced vital capacity (FVC) improved by an average of 4.1% (range, 0.6-9.2) from baseline for a mean difference of 11.6% from natural history data.

Meaningful improvements were also seen in PROs as assessed via the Pediatric Outcomes Data Collection Instrument (PODCI) scales. Improvements were seen in the PODCI global score (range of change from baseline, 7-18), sports score (range, 14-23), transfer score (range, –6 to 3), and upper extremity scores (range, 2-9). Natural history studies would suggest a decline in global (–7.6), sports (–4.7), and transfer (–14.9) scores over 1.5 years.

Safety findings remain consistent with previous 1-year data presented at the 24th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT), May 12-15. These included serious treatment-related adverse events, such as complement-mediated inflammatory response, thrombocytopenia, and transient increases in hepatic transaminases, but these all resolved. Following these events, clinical protocol was amended for subsequent participants to receive prophylactic administration of complement inhibitors and increased glucocorticoid dose.2

“I would say that my philosophy has always been that our job at Solid is to derisk the approach and derisk [Duchenne muscular dystrophy] and continue to innovate and push the envelope as far as science can go. Six, 7 years ago, treating Duchenne patients with gene therapy was simply crazy. Now, it's obvious and everybody's doing it,” Ganot previously told GeneTherapyLive.

1. Solid Biosciences Reports 1.5-Year Data from Patients in the Ongoing IGNITE DMD Phase I/II Clinical Trial of SGT-001. News release. Solid Biosciences.
2. Morris CA, Clary CM, Redican S, et al. IGNITE-DMD phase I/II study of SGT-001 microdystrophin gene therapy for Duchenne muscular dystrophy. Presented at: 2021 American Society of Gene & Cell Therapy Annual Meeting; May 12-15, 2021. Abstract 263
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