Gene Therapy SGT-001 Improves Lung Function in DMD Boys in Trial

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by Margarida Maia |

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Treatment with SGT-001 — Solid Biosciences’ gene therapy candidate for Duchenne muscular dystrophy (DMD) — improves lung function, according to data from the first six patients enrolled in the ongoing IGNITE DMD clinical trial.

The improvements, seen one year after a single infusion of the SGT-001 gene therapy into the vein, included better percent predicted peak expiratory flow, called PEF% predicted — a measure of how fast air can be exhaled from the lungs — and forced expiratory volume in one second, or FEV1% predicted, a measure of the amount of air that can be forced out of the lungs in one second.

These data are being presented in a poster at the Child Neurology Society 50th Annual Meeting, by Oscar H. Mayer, MD, attending pulmonologist and director of the Pulmonary Function Laboratory at Children’s Hospital of Philadelphia. The meeting is being held in Boston Sept. 29 through Oct. 2.

“The improvements in pulmonary function endpoints [goals] seen in the IGNITE DMD study, from baseline [study start] to one year are very promising, especially given that loss of pulmonary function leads to respiratory failure and ultimately death and, to varying degrees, impacts all patients living with Duchenne muscular dystrophy,” Mayer said in a press release.

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DMD is caused by mutations in the DMD gene, which provides instructions for making dystrophin, a protein found in muscles. Its absence or near-absence leads to weakness in the muscles, including those involved in breathing. SGT-001 is designed to deliver a gene encoding a shorter yet functional dystrophin, called microdystrophin, to the body via a viral vector.

IGNITE DMD (NCT03368742) is a Phase 1/2 clinical trial that aims to test if SGT-001 is safe, well-tolerated, and effective in boys with DMD. A total of eight participants have been given SGT-001 to date.

The latest data were obtained from three patients given a low dose of 5E13 vector genomes (vg)/kg, three boys given the high dose of 2E14 vg/kg, and three untreated (control) patients.

PEF% predicted data were available for two of the participants given low-dose SGT-001, two given the high dose, and two controls. In those given SGT-001, improvements ranged from 2.5% to 38.5% at one year. In the control group, the two patients had declines of 1.1% and 18.2%.

For FEV1% predicted, data were available for two boys given low-dose SGT-001, the three patients given high-dose therapy, and the three controls. Among treated patients, improvements ranged from 2.8% to 15.5% at one year. All control patients had declines, ranging from 8.7% to 17%.

“The ability to improve pulmonary function in these patients, especially during a period when the untreated control [group] and natural history data indicate functional decline, is evidence of the potentially meaningful clinical benefit of SGT-001,” said Roxana Donisa Dreghici, senior vice president and head of clinical development at Solid.

Earlier this month, the company had announced positive 1.5-year data showing durable production of microdystrophin in muscles, while also supporting the previously reported benefits in functional abilities and patient-reported outcomes.

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These data were presented at the World Muscle Society 2021 Virtual Congress, in an oral presentation titled “IGNITE DMD Phase I/II ascending dose study of SGT-001 microdystrophin gene therapy for DMD: 1.5-year functional outcomes update,” by Vamshi K. Rao, MD. Rao is an attending physician in neurology at Lurie Children’s Hospital, in Chicago, and assistant professor of pediatrics at the Northwestern University Feinberg School of Medicine.

“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,” Rao said.

The 1.5-year data also showed improved lung function. Specifically, the mean improvement in percent predicted forced vital capacity — the total amount of air exhaled during the FEV test— from the study’s start for the three patients given high-dose SGT-001 was 8.5%, and the mean improvement compared with controls was 16% over the same time period.

“To our knowledge, Solid is the first company to report improvement in multiple assessments of pulmonary function following administration of a Duchenne gene therapy,” said Ilan Ganot, CEO, president, and co-founder of Solid.

“These data add to the data we have previously reported from the IGNITE DMD clinical trial,” Ganot said. “We believe that exploring diverse endpoints will enable us to better understand the totality of the potential benefits that SGT-001 may provide across the spectrum of Duchenne-related disease manifestations.”

Mayer said he is looking forward to further pulmonary function data — and analysis — from IGNITE DMD, saying such results “should provide additional insight into the potential benefit that SGT-001 may provide for patients with Duchenne.”