DMD Trial of Dystrophin Gene Therapy SGT-001 Put on Clinical Hold by FDA

The U.S. Food and Drug Administration has placed a clinical hold on a Phase 1/2 trial testing SGT-001, a dystrophin gene therapy intended to treat Duchenne muscular dystrophy (DMD), after the first patient dosed was hospitalized with a possibly serious reaction.

Solid Biosciences, the therapy’s developer, announced that within days of being given SGT-001 at 5E13 vg/kg of body weight on Feb. 14, the patient, identified as an non-ambulatory male adolescent, showed a drop in platelet count followed by a reduced red blood cell count. An immune system reaction, a cascading sequence of events called “complement activation,” also was evident, the company said in a press release.

No signs of liver damage or a bleeding disorder (coagulopathy) were seen, and the teen responded well to treatment and is now without symptoms. Laboratory tests are showing normal blood parameters, and he is continuing to be observed as an outpatient.

Solid responded to the clinical hold order by suspending further trial enrollment and dosing. It said in the release that it is awaiting information from the FDA regarding how to proceed.

The trial, called IGNITE DMD (NCT03368742), is testing the safety, tolerability and effectiveness of SGT-001 in ambulatory and non-ambulatory Duchenne patients, ages 4 to 17, at the University of Florida. It plans to enroll at least 16 patients, who will be given one of three doses of the gene transfer candidate; effectiveness will be measured through changes in the level of microdystrophin protein in muscles, assessed through biopsies, 12 months after treatment.

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. The therapy uses an adeno-associated viral (AAV) system to deliver a healthy and synthetic version of dystrophin, called microdystrophin, to cells so as to overcome their inability to produce enough of the protein in muscles. As such, it aims to address an underlying cause of DMD.

Solid reported the boy’s possible reaction to the gene therapy to the FDA, classified as a “suspected unexpected serious adverse reaction” or SUSAR, leading to the clinical hold.

The company said it plans to work closely with the regulatory agency, taking whatever steps might be necessary to understand and resolve what happened in this case, and to resume the trial.

SGT-001 was designated an orphan drug by both the FDA and the European Commission as a potential DMD treatment in 2016.