#MDA2022 – SGT-001 Improves Lung, Motor Function After 2 Years

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Boys with Duchenne muscular dystrophy (DMD) treated with the experimental gene therapy SGT-001 in the IGNITE DMD clinical trial continue to show improvements in motor and lung function after two years, according to new data presented at this year’s Muscular Dystrophy Association (MDA) Annual Meeting.

“What we see is consistent, durable improvements in function across all assessments two years after dosing, when compared to expected natural history decline,” said Roxana Dreghici, MD, who discussed the findings in a talk titled “IGNITE DMD Phase I/II Study of SGT-001 Microdystrophin Gene Therapy for DMD: 2-year Outcomes Update.”

Dreghici is head of clinical development at Solid Biosciences, the company developing SGT-001.

DMD is caused by mutations in the gene that provides instructions for making dystrophin, a protein that is critical for maintaining the health of muscle cells. SGT-001 is designed to use a specially engineered viral vector to deliver a gene encoding microdystrophin — a shortened, but still functional version of the dystrophin protein — to the body’s muscle cells.

Solid Biosciences is the sponsor of the Phase 1/2 clinical trial IGNITE DMD (NCT03368742), which is testing the therapy candidate’s safety and efficacy in children with DMD, ages 4 to 17, who are able to walk (ambulatory).

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The first three participants in the trial were treated with a single infusion of SGT-001 at a dose of 5E13 vector genomes per kilogram (vg/kg). An additional six participants were treated at a dose of 2E14 vg/kg.

The study’s main goal is to evaluate safety. All nine of the boys given SGT-001 had nausea as a side effect of treatment, and nearly all of them also experienced vomiting and fever. These side effects “are not unexpected with a gene therapy,” Dreghici said. Some laboratory abnormalities, particularly low levels of platelets and red blood cells, also were reported.

In all SGT-001-treated boys, treatment with the gene therapy led to activation of the complement cascade — a group of immune proteins that help the body fight off infections. This led to three serious adverse events: two systemic inflammatory responses, and one case of acute thrombocytopenia, which is low platelet levels.

A serious event of hepatitis (liver inflammation) resolved rapidly after a temporary increase in steroid doses. Another serious adverse event of intestinal infection (giardiasis) was determined to be unrelated to SGT-001.

“All SAEs [serious adverse events] were resolved quite soon after they happened,” Dreghici said. She also noted that all reported treatment side effects occurred within three months of gene therapy administration, with no further events at longer follow-up times, which ranged from four months to nearly four years.

Biopsy data showed that SGT-001 treatment led to an increase in microdystrophin levels in muscle tissue, which was sustained up to two years after treatment. Notably, analyses suggest that microdystrophin levels in muscle are increasing over time in the patients, as levels were generally higher at later timepoints. Also, data from the biopsies showed “very mild or no” active damage in muscle cells, Dreghici said.

Motor function in the study was assessed with the North Star Ambulatory Assessment (NSAA) and 6-Minute Walk Test. At up to two years post-treatment with the high dose of SGT-001, scores on these assessments among the three patients with available data were largely stable over time. Notably, since DMD is a progressive disease, these scores would be expected to gradually worsen over time in the absence of treatment.

“What we expect to see in untreated patients is a decline which is quite steady,” Dreghici said. By contrast, in SGT-001-treated patients, “we see consistent and stable motor function … at two years post-dosing,” she said.

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At the two-year mark, compared with what would be expected without treatment, patients given SGT-001 could walk more than 100 meters (328 feet) farther in six minutes. Similarly, NSAA scores were more than four points higher than would be expected without treatment.

After treatment with SGT-001, average scores on two assessments of lung function — forced vital capacity and peak expiratory flow, both measuring airflow from the lungs — were improved compared with scores prior to gene therapy. This increase was sustained out to two years post-dosing.

The three boys treated for at least two years also reported notable improvements on the Pediatrics Outcomes Data Collection Instrument (PODCI), which assesses children’s own perceptions about their health.

Like motor function scores, lung function and PODCI scores would normally be expected to gradually get worse over time, Dreghici noted.

“We continue to see sustained motor function … when compared to natural history decline. We see improved pulmonary function … compared to baseline [the study’s start] and to natural history, and we continue to see meaningful improvements in patient-reported outcomes,” Dreghici concluded.


Note: The Muscular Dystrophy News Today team is providing coverage of the 2022 MDA Clinical and Scientific Conference March 13–16. Go here to see the latest stories from the conference.