FDA keeps Solid Bio's troubled Duchenne MD gene therapy on clinical lockdown in latest setback
Much-maligned Solid Biosciences received yet another spate of bad news late Friday regarding its Duchenne muscular dystrophy gene therapy program.
It’s been almost nine months since the FDA announced a second clinical hold on Solid Bio’s Phase I/II trial for an AAV-based Duchenne MD treatment. And after extending that hold in May, US regulators again decided they needed more info with another extension on Friday.
Investors reacted somewhat poorly to the news as the Cambridge, MA-based biotech’s stock price, which peaked at over $50 per share in September 2018, fell about 2.5 percent to $2.70 after Friday’s closing bell.
Solid Bio’s notoriety dates all the way back to its IPO in January 2018 when CEO Ilan Ganot did not disclose its lead program was placed on a partial clinical hold until the company was wrapping up pricing. Around that time, the company also announced that gene therapy pioneer James Wilson resigned from its scientific advisory board after concerns arose in animal testing about severe toxic reactions, including liver damage, in high AAV doses.
A few months later, the FDA placed its first clinical hold on the study after the first patient treated experienced a “decrease in platelet count followed by a reduction in red blood cell count, transient renal impairment and evidence of complement activation,” according to a statement from the time.
But that hold was lifted in June 2018, as Solid Bio changed the study to add IV glucocorticoids after treatment, amp up monitoring activity and provide eculizumab on an as-needed basis to fight any complement activation that may occur in future.
Things seemed to be looking up, relatively speaking, until February 2019 when the Phase I/II dose-ascending trial flopped in the clinic as biopsies of patients “showed low levels of microdystrophin protein expression.” Later that year, the FDA placed its current hold on the trial after another patient experienced serious adverse effects that closely resembled the earlier setback.
In order to weather that storm, Solid Bio laid off a third of its staff including its CMO and COO. Responding to the hold’s extension in May, the biotech proposed clinical changes to the trial “designed to enhance patient safety,” and committed to improvements in the manufacturing process.
SVB Leerink saw a silver lining at the time, noting that the FDA did not comment on any of the company’s clinical strategy proposals. The changes that were ultimately made, however, did not satisfy regulators as the hold remains in place.
Ganot, a former JP Morgan investment banker, is a Duchenne MD dad and has said that has driven him to find a cure for the rare, lethal disease. By introducing a synthetic dystrophin transgene construct called microdystrophin, via a viral vector, Ganot and Solid Bio hope to prove it can do what competitors like Sarepta and others have been trying for with one decisive intervention.