FDA, in its letter, said that Solid Biosciences, the therapy’s developer, had addressed all questions of concern that led to the clinical hold, which was placed in March after the company reported a first patient dosed in the trial was hospitalized due to adverse and unexpected events.
These included a decrease in platelet and red blood cell counts, and transient problems with the kidneys. The patient also showed an activation of the complement system, a part of the immune system.
He responded to standard care, including a modified treatment with steroids and short-term treatment with Soliris (eculizumab), a complement inhibitor. He remained stable and “generally asymptomatic” throughout this period — classified as a serious adverse event — and all was “fully resolved,” a company press release reported.
The trial, called IGNITE DMD (NCT03368742), will now resume enrolling patients at its one Florida site.
“We believe SGT-001 has the potential to offer significant benefit to patients with DMD, regardless of their age or stage of disease,” Ilan Ganot, founder and chief executive officer of Solid Biosciences, said in the release.
“We are pleased to have been able to provide the FDA with a comprehensive response resulting in the removal of the clinical hold so we can continue development of this important potential treatment,” he added.
As part of the lifting of the clinical hold, Solid has changed the study’s design and will now administer glucocorticoids intravenously (directly to the blood) in the first weeks following administration of SGT-001. Patients will be closely monitored, with a special attention for complement activation.
The amended protocol also includes treatment with Soliris in the cases where complement activation is observed.
IGNITE DMD will test the safety, tolerability and effectiveness of SGT-001 in ambulatory and non-ambulatory Duchenne patients, ages 4 to 17, at the University of Florida.
Effectiveness will be measured through changes in the level of microdystrophin protein in muscles, assessed through biopsies, 12 months after treatment.
The protocol includes a possible intermediate assessment of SGT-001’s efficacy by muscle biopsy at 45 days post-treatment.
The company now expects to release the first results in the second half of 2019.
SGT-001 is a synthetic version of the DMD gene that produces dystrophin, a protein found in cardiac and skeletal muscles and responsible for movement.
Using an adeno-associated viral (AAV) system, the therapy aims to deliver a healthy and synthetic version of dystrophin, called microdystrophin, to cells to overcome their deficient production of the dystrophin protein muscles.
“Gene therapy has the potential to dramatically change the course of DMD and may offer long-term benefit for those who suffer from this devastating disease,” said Barry Byrne, MD, director of the University of Florida Powell Gene Therapy Center.
“After a thorough analysis of the clinical and laboratory data for the patient, I am confident the event was easily monitored and medically manageable. Our patient quickly returned to his normal activities and planned study assessments,” Byrne said. “We look forward to continuing the IGNITE DMD study and providing additional children and adolescents with this promising investigational therapy.”