Gene Therapy SGT-001 Shows Signs of Microdystrophin Production in Muscles of Boys in IGNITE DMD Trial

Preliminary results of a Phase 1/2 study into the gene therapy candidate SGT-001 in Duchenne muscular dystrophy (DMD) patients show low levels of microdystrophin in patients’ muscles after three months of treatment with an initial low dose and continued safety, Solid Bioscience, the therapy’s developer, reported.

Continued safety was also evident, the company said in a press release. It added that the trial will begin to administer higher doses of SGT-001, in keeping with its design, as soon as possible.

“We believe that SGT-001 will be a meaningful treatment for patients with DMD and are confident we have the right approach in place to evaluate its potential at higher doses. We have already begun working to expedite the planned dose escalation strategy outlined in our clinical trial protocol,” Ilan Ganot, Solid Bioscience’s CEO and president, said in the release.

DMD patients either make very little, or lack entirely, the muscle protein dystrophin due to mutations in the DMD gene, resulting in muscle degeneration. SGT-001 is adeno-associated viral (AAV) vector-mediated gene transfer therapy that is designed to deliver a synthetic version of dystrophin, called microdystrophin, to muscles. The aim is to support the production of a working protein similar to dystrophin.

Preclinical results have shown that SGT-001 has the potential to slow or halt progression of DMD, regardless of mutation or disease stage.

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The open-label study, called IGNITE DMD (NCT03368742), is testing the safety, efficacy, and tolerability of a single intravenous (IV) infusion of SGT-001 in ambulatory children and non-ambulatory teenagers, ages 4 to 17. Efficacy will be evaluated by testing for microdystrophin production through muscle biopsy samples.

A total of 16 Duchenne patients will be enrolled, and randomly assigned to treatment groups or to serve as controls. Control group patients will be given the gene therapy at its recommended dose after one year of data is collected, if they continue to meet treatment criteria.

To date, six boys have been enrolled, three in the treatment and three in the control group. The trial is continuing to recruit eligible patients at its University of Florida site, and all will be followed for about two years.

These early results are based on three-month biopsy data from the three treated patients, each of whom received the study’s lowest planned dose — 5E13 vg/kg — of SGT-001.

Researchers used two methods to detect the microdystrophin protein in the boys’ muscles: Western blot, which detects specific proteins, and immunofluorescence, which detects antigens in tissues and cells using antibodies.

Results showed low levels of microdystrophin in one patient using each technique. In this boy, microdystrophin was present in about 10 percent of muscle fibers via immunofluorescence and in less than 5 percent of fibers using Western blot. The researchers also found signs of two proteins that require microdystrophin for stability — neuronal nitric oxide synthase and beta-sarcoglycan — suggesting that the protein is working as intended.

Microdystrophin was also detected in the other two treated boys at “very low levels” using immunofluorescence, but it could not be detected by Western blot.

“The patients who have received SGT-001 as part of the IGNITE DMD clinical trial are all doing well, and we are encouraged to explore higher doses moving forward,” said Barry Byrne, MD, the study’s principal investigator.  “It is extremely important to advance innovative research with the ultimate goal to bring therapies to patients with Duchenne muscular dystrophy.”

Full data for this Phase 1/2 study is expected to be collected in March 2020. In total, the trial calls for testing of three dose levels.

SGT-001 was designated an orphan drug as a potential DMD treatment by both the  U.S. Food and Drug Administration (FDA) and the European Commission (EC) in October 2016. The FDA has also placed the therapy on “fast track” to speed its development in trials and its possible regulatory review, the release reported.