Solid Biosciences announced that the U.S. FDA has notified the company that the Phase I/II IGNITE DMD study has been placed on clinical hold. This marks the second clinical hold issued by the FDA this year. The IGNITE DMD study is evaluating SGT-001, a gene transfer therapy, in boys with Duchenne muscular dystrophy.
According to the company, six patients to date have been dosed with SGT-001. This includes three patients in the first cohort at a 5E13 vg/kg dose, who are reported to be doing well and are being followed per the study protocol. Three patients were subsequently dosed in the second cohort at a 2E14 vg/kg dose. The first two of these patients is also reportedly doing well and being followed per study protocol.
The third patient in the 2E14 vg/kg cohort, dosed in late October, experienced a serious adverse event (SAE) 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. Neither cytokine- nor coagulopathy-related abnormalities were observed.
Solid Biosciences reported the event to the FDA and the study Data Safety Monitoring Board (DSMB). The FDA notified the company that the study has been placed on clinical hold. Solid will work with the FDA to resolve the hold and determine next steps for IGNITE DMD.
In March of 2018 the FDA placed a clinical hold on the trial following the report of a serious adverse event. That hold was lifted in June 2018 after the company addressed the FDA’s concerns. Earlier this year the company reported more adverse effects related to SGT-001. However, the adverse effects were resolved, and the trial continued as planned.
SGT-001 is a novel adeno-associated viral (AAV) vector-mediated gene transfer under investigation for its ability to address the underlying genetic cause of DMD, 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 DMD, regardless of genetic mutation or disease stage.
SGT-001 has been granted Rare Pediatric Disease Designation in the United States and Orphan Drug Designations in both the United States and European Union.
About Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a progressive form of muscular dystrophy that occurs primarily in males, though in rare cases may affect females. DMD causes progressive weakness and loss (atrophy) of skeletal and heart muscles. Muscle weakness is usually noticeable by 3 or 4 years of age and begins in the hips, pelvic area, upper legs, and shoulders. Most children with DMD use a wheelchair full time by age 13. Heart and respiratory muscle problems begin in the teen years and lead to serious, life threatening complications. There is no cure for DMD and treatment focuses on controlling symptoms and reducing complications.