Shares of Solid Biosciences have plunged more than 71 percent after the company revealed early data from a Phase I/II trial that showed low doses of its gene therapy treatment may lack the potential to be as effective a treatment for Duchenne muscular dystrophy as current products on the market.
Shares of Solid Biosciences have plunged more than 71 percent after the company revealed early data from a Phase I/II trial that showed low doses of its gene therapy treatment may lack the potential to be as effective a treatment for Duchenne muscular dystrophy as current products on the market.
This morning, Cambridge, Mass.-based Solid Biosciences released data from a three-month biopsy taken during the Phase I/II IGNITE DMD trial evaluating the safety and efficacy of SGT-001, a novel adeno-associated viral (AAV) vector-mediated gene transfer. The biopsy showed low levels of microdystrophin protein expression, Solid said in its announcement. 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 The company plans to engage with the patients involved with the trial to escalate the doses given to patients as soon as possible. As a result, company stock fell to $6.34 in early trading. It closed at $22.34 on Wednesday.
The early data was taken from the first three patients dosed with SGT-001. Each of these patients had been given the lowest dose outlined in the study protocol. The company said it was able to detect microdystrophin below the five percent level of quantification of the assay and in approximately 10 percent of fibers via immunofluorescence. For that one patient, there were also signs of co-localization of neuronal nitric oxide synthase and beta-sarcoglycan associated with microdystrophin expression, the company said. In the other two patients, microdystrophin was detected via immunofluorescence at very low levels, but it was undetectable via western blot assay, the company said.
Ilan Ganot, co-founder, chief executive officer and president of Solid Biosciences, said the company believes that the gene therapy program SGT-001 will be a meaningful treatment for DMD patients. Ganot said the company is confident it has “the right approach in place” to evaluate the potential efficacy of the therapy at higher doses.
“We have already begun working to expedite the planned dose escalation strategy outlined in our clinical trial protocol. This strategy is further supported by our scalable manufacturing process, from which we have sufficient drug product available to dose escalate without delay,” Ganot said in a statement.
Six patients have been enrolled in IGNITE DMD, three to the active treatment group and three to the delayed treatment control group. The safety profile of SGT-001 remains unchanged and all patients continue to be followed per the study protocol.
The early data that has so disappointed investors is not the first setback Solid Biosciences has seen with its SGT-001 DMD program. In March 2018, the U.S. Food and Drug Administration placed a clinical hold on the IGNITE DMD trial over safety concerns. That clinical hold followed closely on the heels of a partial clinical hold the federal regulatory agency placed on its product in November 2017. The latest clinical hold was lifted in June after the company addressed all of the concerns and questions the FDA had.
As Solid continues to move forward with the dose escalation, the company lags behind competitor Sarepta Therapeutics. In October, that company, also based in Cambridge, reported that patients treated with its DMD gene therapy showed “robust expression of transduced micro-dystrophin.” In all patients, expression of micro-dystrophin was associated with significant expression and up-regulation of the dystrophin-associated protein complex, an additional indication of functionality of dystrophin, Sarepta said.
