FDA Lifts Clinical Hold on Solid Bio DMD Gene Therapy Trial: Shares Jump
Shares of Solid Biosciences have jumped 11 percent in premarket trading after the company announced the U.S. Food and Drug Administration (FDA) has lifted a clinical hold on the company’s Phase I/II clinical trial gene therapy treatment for Duchenne muscular dystrophy (DMD).
The FDA placed the hold on the trial of Solid’s investigational microdystrophin gene transfer, SGT-001, in March following concerns about the drug’s safety following the first dosing of a patient with the treatment. This morning the Cambridge, Mass.-based company said the FDA has acknowledged in a letter that Solid Biosciences has “satisfactorily addressed all clinical hold questions.” The patient experienced a decrease in platelet count followed by a reduction in red blood cell count, transient renal impairment and evidence of complement activation, the company said. There were no signs of bleeding or clotting abnormalities and no laboratory evidence of liver dysfunction. Following standard medical care, the patient remained “clinically stable and generally asymptomatic throughout the event, which fully resolved,” according to a statement.
The company said it plans to resume the clinical trial and aims to “reinitiate enrollment as quickly as possible.”
“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,” Ilan Ganot, founder and chief executive officer of Solid Biosciences said in a statement.
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. SGT-001 is designed to deliver a synthetic dystrophin gene, called microdystrophin, to the body of DMD patients. Microdystrophin encodes for a functional protein surrogate that is expressed in muscles and stabilizes essential associated proteins, including neuronal nitric oxide synthase (nNOS), the company said. The company’s belief is that SGT-001 could be a one-time treatment for the devastating disease regardless of genetic mutation or stage of the disease. DMD is associated with specific errors in the gene that codes for dystrophin, a protein that plays a key structural role in muscle fiber function. One of the most common fatal genetic disorders, DMD affects approximately one in every 3,500 boys born worldwide. The condition is universally fatal, and death usually occurs before the age of 30.
Solid said it has made changes to the IGNITE DMD trial protocol in connection with the FDA decision to lift the clinical hold. The trial will include the addition of IV glucocorticoids in the initial weeks following the administration of SGT-001. The trial will also include enhanced monitoring measures that include a panel for complement activation. The amended protocol also specifies that eculizumab (Alexion’s Soliris) will be available as a treatment option if complement activation is observed.
Due to the delay of the IGNITE DMD trial from the clinical hold, Solid said it expects to report initial data from a pre-specified interim analysis in the second half of 2019.
As part of its clinical efforts, Solid said it intends to enroll and dose several children prior to dosing additional adolescent DMD patients. 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, the company said.
The FDA placed the clinical hold on Solid’s lead therapy months after the company disclosed that gene therapy expert James Wilson, a key member of the company’s scientific advisory board, to resign from the company due to safety concerns. Solid said Wilson “resigned from our Scientific Advisory Board citing emerging concerns about the possible risks of high systemic dosing of AAV.”