Two More Patients Dosed in Solid Trial of DMD Gene Therapy SGT-001

Two more participants have been dosed in the IGNITE DMD clinical trial, bringing to eight the total number of Duchenne muscular dystrophy (DMD) patients thus far given Solid Biosciences‘ investigational gene therapy SGT-001.

The U.S. trial is testing SGT-001’s safety and efficacy in boys with DMD ages 4 to 17.

Solid noted that the eighth patient experienced a serious adverse event (SAE), but is recovering.

“We are pleased to have progressed with dosing patients in our IGNITE DMD trial and will continue monitoring patient outcomes,” Ilan Ganot, Solid’s CEO, president, and co-founder, said in a press release.

DMD is caused by mutations that lead to a functional lack of the protein dystrophin, which is important for muscle health. SGT-001 is designed to deliver a gene encoding microdystrophin — a shortened, but functional version of dystrophin — to muscle cells using an engineered viral vector. The therapy is given via a single infusion into the bloodstream.

IGNITE DMD (NCT03368742) is a Phase 1/2 trial, sponsored by Solid, that is testing the experimental gene therapy at four study sites in boys with DMD. Data from the first six participants dosed in the trial have been positive, indicating that the treatment improved physical function and patient-reported outcomes.

The two additional participants now dosed each were given 2e14 vector genomes (vg)/kg of SGT-001. These boys received doses of the gene therapy made using an updated manufacturing process; both were dosed under an amended clinical protocol that aims to maximize participants’ safety.

The seventh participant was dosed uneventfully and is continuing to do well, Solid reports.

However, the eighth participant, dosed this April, experienced a serious adverse event that was deemed by the study’s investigators as related to treatment. Specifically, the adverse event was an abnormal inflammatory response.

“It is important to note this SAE was described in our investigators brochure and not considered unexpected,” Solid stated in a letter to the Duchenne community posted on the company’s website.

“We are pleased to share this patient is home with his family and continues to improve with laboratory values back to normal or continuing to trend towards normal at his 30-day post dosing visit,” the letter said.

Solid is continuing to analyze data on these participants. The company also is continuing discussions with the U.S. Food and Drug Administration and the trial’s data safety monitoring board.

Meanwhile, new data from the fourth, fifth, and sixth trial participants — all of whom received 2e14 vg/kg of SGT-001 — also was reported by Solid.

Muscle biopsies from these patients showed that the therapy led to increased levels of microdystrophin protein. Specifically, the biopsies were analyzed using two methods: Western blot, which assesses the total amount of protein, and immunofluorescence, which looks at the number of individual cells that are expressing the protein.

At 90 days (about three months) after treatment, the three participants had increased microdystrophin expression. Their levels were up to about 17.5% of normal dystrophin, as measured by Western blot, and 10-70% of positive muscle fibers as assessed by immunofluorescence.

Biopsies taken more recently — from one to two years after the treatment — broadly found that microdystrophin levels had either stayed the same or increased from the 90-day analysis. Assessments of other proteins related to dystrophin also supported the functionality of SGT-001. Further observations indicated minimal progression of muscle deterioration, the company reported.

In addition, levels of creatine kinase — a marker of muscle injury — were substantially decreased in these boys at one year post-treatment.

These findings recently were presented at the annual meeting of the American Society of Gene & Cell Therapy, in a presentation titled “IGNITE-DMD Phase I/II Study of SGT-001 Microdystrophin Gene Therapy for Duchenne Muscular Dystrophy” (#263).

“We are excited by the durability of the microdystrophin protein observed in these patients, and the potential for the meaningful impact this may have on their lives,” Ganot said.

“These data in totality continue to support the ongoing investigation of SGT-001 as a transformative therapy for DMD,” the scientists wrote.

Solid also has announced the initiation of a next-generation gene therapy program for DMD, called SGT-003. Like SGT-001, SGT-003 is a gene therapy that seeks to deliver a gene encoding microdystrophin to the body’s muscle cells. The new gene therapy was essentially designed to more effectively deliver the genetic payload to muscle cells, while lessening the amount of gene therapy that ends up in the liver.