The FDA has lifted the second of two clinical holds on Solid Biosciences’ phase 1/2 trial in Duchenne muscular dystrophy, following the resolution of safety and manufacturing concerns, and the company has begun working to resume enrollment.
Solid amended its study protocol to include intravenous glucocorticoids in the weeks immediately following the administration of its investigational DMD treatment, SGT-001, after the trial’s first patient was hospitalized with an immune system reaction and decreased blood counts.
In addition, the company launched enhanced monitoring measures—including a panel for complement activation, a type of innate immune system response—and plans to make available Alexion Pharmaceuticals’ immunosuppressant Soliris (eculizumab) if complement activation occurs.
According to Solid, a letter from the FDA said the Cambridge, Massachusetts-based company satisfactorily addressed all the agency’s concerns. The study plans to enroll and dose several children before enrolling additional adolescents, and now expects to report initial interim findings in the second half of next year.
SGT-001 is a viral vector-mediated microdystrophin gene transfer that aims to address the underlying mutations in the dystrophin gene that result in the lack of the protein. The microdystrophin encodes for a functional protein surrogate expressed in muscles that helps stabilize associated proteins.
The company disclosed the first partial clinical hold in January—announced the same day Solid listed its IPO, even though the FDA had informed the company of the hold the previous November, which stopped the study from proceeding with higher doses.
The biotech dropped the price of its offering to $16 per share, down from its planned $18-$19, and increased the number of shares from 5.9 million to 7.8 million.
That partial hold was lifted in April, after the company fixed manufacturing issues related to the higher doses—but not before trial was put on hold completely in March, after the study’s first patient in the lower-dose cohort was hospitalized.
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The FDA classified the event as a suspected, unexpected, serious adverse reaction, or SUSAR; the patient had decreased platelet and red blood cell counts, transient renal impairment and complement activation. He showed no evidence of liver dysfunction, and would later show no symptoms following standard treatment, the company said.
“After a thorough analysis of the clinical and laboratory data for the patient, I am confident the event was easily monitored and medically manageable,” said Barry Byrne, director of the University of Florida’s Powell Gene Therapy Center. “Our patient quickly returned to his normal activities and planned study assessments.”
“We believe SGT-001 has the potential to offer significant benefit to patients with DMD, regardless of their age or stage of disease,” Solid’s founder and CEO, Ilan Ganot, said in a statement. “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.”