A new clinical hold following serious adverse events are the latest in a string of setbacks for Solid Biosciences and the development of its gene therapy for Duchenne muscular dystrophy.
Last year, the company resolved partial and full clinical holds for its phase 1/2 study of SGT-001, its single-dose, AAV-mediated microdystrophin therapy, after addressing safety and manufacturing concerns.
Now, that trial is on hold again after the sixth and latest patient saw decreases in red blood cell and platelet counts, activation of the complement immune system response, acute kidney injury and cardio-pulmonary insufficiency.
The seven-year-old boy, dosed in late October and being treated at the University of Florida, was the third in the trial’s second cohort to receive a higher dose of SGT-001—2 x 10^14 vector genomes per kilogram, or about 200 trillion, compared to the first cohort’s 5 x 10^13 vg/kg. He is currently recovering and continuing to improve, and no bleeding or coagulation-related events were observed, according to the company.
After reporting the adverse event, the company received a phone call from the FDA the next day informing them of the clinical hold; Solid Bio said it is currently waiting for formal written communications from the agency. In the meantime, the company is going through its clinical and manufacturing data, and testing for possible infections, to help develop a hypothesis explaining the events. Solid Bio’s stock dropped 70% in premarket trading after the news.
“We are basically turning over every stone to figure out the best path forward, including talking to regulators and the like,” CEO Ilan Ganot said on a conference call following the release. “We don't just learn from every patient, we learn from every hour of every patient. We're accumulating meaningful amounts of data about each of them.”
The other patients in the study are doing well and are being assessed, Ganot said. The company previously instituted additional safety and monitoring measures after the trial’s first patient was hospitalized with an immune system reaction and decreased blood counts. While the latest patient’s events were similar and followed a comparable time course, this time the reactions progressed further, the company said.
In January 2018, Solid Bio revealed the trial’s first partial clinical hold at the same time as the company’s IPO and debut on the Nasdaq. It moved forward with a cut-price offering for an upsized stake, after receiving heavy criticism for not disclosing the notice earlier in its December prospectus or subsequent filings.
The partial hold was upgraded to a full clinical hold later that spring, over manufacturing concerns related to higher doses. The company was able to resume enrollment by mid-June 2018 after amending its study protocol.
But the company’s stock took another hit this past February, after SGT-001 demonstrated low levels of microdystrophin expression in an analysis of the trial’s lower dose. At the time, Ganot said that the company is confident in its approach to evaluate higher doses, alongside its scalable manufacturing process. Going forward, Solid Bio said it still plans to report additional biomarker data from the study before the end of the year.
“In the coming weeks, we anticipate that we will have a better understanding of the biological activity and potential benefit of SGT-001,” Ganot said Tuesday. “We look forward to sharing this additional data and working with the FDA to resolve the clinical hold and determining next steps for the program.”