Rare Daily Staff

The U.S. Food and Drug Administration has lifted the clinical hold on Solid Biosciences’ phase 1/2 clinical trial for its experimental microdystrophin gene transfer, SGT-001, for the treatment of the rare, progressive, fatal disease Duchenne muscular dystrophy.

The FDA notified the company that it addressed all clinical hold questions. Solid has begun activities to resume the clinical trial and plans to reinitiate enrollment as quickly as possible.

“We believe SGT-001 has the potential to offer significant benefit to patients with DMD, regardless of their age or stage of disease,” said Ilan Ganot, CEO of Solid. “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.”

The FDA placed the hold on Solid’s trial in March after the first patient dosed in the trial was hospitalized several days after administration of the therapy due to a decrease in platelet count followed by a reduction in red blood cell count, transient renal impairment, and evidence of immune response to the therapy. There were no signs of bleeding or clotting abnormalities and no laboratory evidence of liver dysfunction. The patient received standard medical care, a modified steroid regimen, and a limited course of eculizumab for the observed complement activation. He remained clinically stable and generally asymptomatic throughout the event, which fully resolved.

In connection with the lifting of the clinical hold, Solid has made changes to the study’s protocol, including the addition of IV glucocorticoids in the initial weeks post administration of SGT-001 and enhanced monitoring measures that include a panel for complement activation. The amended protocol also specifies that eculizumab will be available as a treatment option if complement activation is observed.

SGT-001, Solid’s lead experimental therapy, is an adeno-associated viral vector-mediated gene transfer that is designed 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 synthetic dystrophin transgene, called microdystrophin. This microdystrophin encodes for a functional protein surrogate that is expressed in muscles and stabilizes essential associated proteins. Data from Solid’s preclinical program suggest that SGT-001 has the potential to slow or stop the progression of DMD, regardless of genetic mutation or disease stage.

The company plans to enroll and dose several children prior to dosing additional adolescents. In addition, Solid now has the choice to obtain the intermediate muscle biopsy at 45 days post administration of SGT-001 to collect additional information about the time course of microdystrophin expression.

As a result of the clinical hold, Solid now expects to report initial data from a pre-specified interim analysis of data from the study in the second half of 2019.

June 18, 2018
Photo: Ilan Ganot, CEO of Solid Biosciences