RARE Daily

Solid Reports New Data from DMD Clinical Trial, Resumes Patient Dosing

March 16, 2021

Rare Daily Staff

Solid Biosciences reported encouraging interim functional and biomarker data, and patient reported outcome measures from six patients after treatment in the ongoing IGNITE DMD phase 1/2 clinical trial of its lead gene therapy candidate, SGT-001.The company also announced that patient 7 in IGNITE DMD was safely dosed, with transient and manageable adverse events, none of which were serious. Patient 7 was the first patient dosed in IGNITE DMD SGT-001 manufactured with its second-generation process. Additionally, the six patients previously dosed showed no new drug-related safety findings, 17-37 months post dosing. Solid says totality of data collected and the re-initiation of dosing support the continued enrollment of patients into the IGNITE DMD study.

Solid will present these data in an oral session and at a company-sponsored symposium at the 2021 MDA Virtual Clinical & Scientific Conference on Thursday, March 18.

“The safe dosing of the seventh patient gives us increased confidence in our dosing strategy as we move forward with clinical development in the IGNITE DMD clinical trial,” said Ilan Ganot, CEO, president and co-founder of Solid Biosciences. “We look forward to continuing to dose patients and reporting clinical outcomes from additional patients in the second half of 2021.”

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle degeneration and weakness that primarily affects boys with symptoms beginning as early as three years of age. It is caused by an absence of dystrophin, a protein that helps keep muscle cells intact. Progressive muscle weakness in the lower limbs spreads to the arms, neck and other areas of the body. The condition is universally fatal, and death usually occurs before the age of 30 generally due to respiratory or cardiac failure.

SGT-001 is a novel adeno-associated viral vector-mediated gene transfer therapy designed to address the underlying genetic cause of Duchenne. Duchenne is caused by mutations in the dystrophin gene that result in the absence or near absence of dystrophin protein. SGT-001 is a systemically administered candidate that delivers a synthetic dystrophin gene, called microdystrophin, to the body. This microdystrophin encodes for a functional protein surrogate that is expressed in muscles and stabilizes essential associated proteins, including neuronal nitric oxide synthase nNOS. Data from Solid’s preclinical program suggests that SGT-001 has the potential to slow or stop the progression of Duchenne, regardless of genetic mutation or disease stage.

Solid’s trial has been dogged by problems with the U.S. Food and Drug Administration placing a clinical hold on the program in November 2019 after a seven-year-old boy dosed in the study experienced a serious adverse event deemed related to the study drug that was characterized by complement activation, thrombocytopenia, a decrease in red blood cell count, acute kidney injury, and cardio-pulmonary insufficiency.The hold was lifted in October 2020 after Solid changed its manufacturing process to allow target dosing to be achieved with fewer viral particles thus reducing the total viral load.

Solid says interim data from six patients dosed previously to the hold provide evidence of a potential benefit of SGT-001 in functional endpoints of North Star Ambulatory Assessments (NSAA), 6-minute walk test (6MWT), pulmonary function tests (PFTs), and clinically validated patient reported outcome measures (PROMs).

The company also reported that Patient 7 was safely dosed with the new formulation of SGT-001, and experienced transient and manageable adverse events, none of which were serious; the six patients previously dosed showed no new drug-related safety findings 17-37 months post dosing; and screening and enrollment of patients into IGNITE DMD will continue.

The data reported were collected from the first six patients dosed in IGNITE DMD 12 to 24 months after treatment and include data from three patients dosed at the low dose (5E13 vg/kg) and three patients dosed at the high dose (2E14 vg/kg). Data from the delayed treatment cohort, analyzed as an untreated control cohort, were evaluated alongside representative natural history data. The six patients ranged in age from five to 14-years-old at baseline. These data have been previously shared with FDA, as well with members of the IGNITE DMD Data Safety Monitoring Board and clinical consultants.

While functional data was positive, biomarker data was mixed. Creatine kinase (CK) assessments, a marker of damage, in the six patients showed average sustained CK decline of approximately 50 percent in the high-dose cohort, while the low-dose cohort saw an average CK increase of about 166 percent, and the control group had an average CK increase of about 17 percent. These six patients are the only ones to receive the first version of SGT-001 as all new enrollees will be given Solid’s new construct that will halve the viral load.

SGT-001 has been granted Rare Pediatric Disease Designation, or RPDD, and Fast Track Designation in the United States and Orphan Drug Designations in both the United States and European Union.

Photo: Ilan Ganot, CEO, president and co-founder of Solid Biosciences

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