- The Food and Drug Administration lifted a clinical hold on an experimental gene therapy for Duchenne muscular dystrophy, allowing Solid Biosciences to resume testing two months after the first patient treated experienced an unexpected adverse event.
- That patient has since recovered, Solid said, and changes to the study's protocol proposed by the company appear to have given the FDA confidence in green lighting a trial restart.
- Solid now expects interim data from the Phase 1/2 trial to read out in the second half of 2019 — about half a year later than originally expected. Shares in the Cambridge, Massachusetts-based biotech jumped 11% in response on Monday, fully erasing the effects of a sharp sell-off in March when the hold was first announced.
After an inauspicious start to its life as a clinical-stage biotech, Solid is back on firmer ground.
According to the company, the FDA found it had satisfactorily addressed all questions posed by the clinical hold, easing concerns about the profile of Solid's gene therapy.
In February, Solid dosed the first patient in its DMD study with the micro-dystrophin gene transfer treatment — a milestone for the field by Solid's account. But that patient experienced a drop in platelet counts and was later admitted to the hospital, where low red blood cell counts and transient renal impairment were observed. Even more worrisome were signs of complement activation, suggesting a possible immune response.
Resultingly, the FDA placed a clinical hold and asked for a more detailed assessment of the patient case.
In its update Monday, Solid noted that the patient "remained clinically stable and generally asymptomatic throughout the event, which fully resolved" following administration of steroids and a limited course of Alexion's Soliris (eculizumab).
Per the protocol changes that the FDA signed off on, patients in the study will initially be given intravenous glucocorticoids following dosing of the gene therapy. Enhanced monitoring will include a panel to test for complement activation and specifies for Soliris to be available for potential use. A biopsy may also be taken at 45 days post-administration to gauge how the therapy is working.
Notably, Solid agreed with the FDA to test its treatment in an unspecified number of ambulatory children before moving on to test in non-ambulatory adolescents. (The first patient treated was non-ambulatory.)
"We remain committed to the non-ambulatory population and plan to continue to evaluate SGT-001 in non-ambulatory adolescents later in the clinical trial," said Solid CEO Ilan Ganot on a June 18 conference call with analysts.
That shift to younger patients could have knock-on effects for future efficacy read-outs, though.
"Considering that [Solid] is now dosing younger [patients] who could benefit more, and is taking biopsies at an earlier time point, we believe this increases the likelihood that [Solid] reports more competitive efficacy earlier on," wrote Leerink analyst Joseph Schwartz in a June 18 note to investors.
The safety concerns aren't the only issue Solid has faced. Work by prominent gene therapy researcher James Wilson, who left Solid's advisory board, and others has raised concerns about the use of high doses of adeno-associated virus (AAV) to deliver gene therapies.
In restarting its trial, Solid will keep the administered dose the same as before, at 50,000,000,000,000 vg/kg.
Other companies are also moving forward with potentially competing gene therapies for DMD.
Sarepta Therapeutics, a rival of Solid's with a marketed injectable drug for DMD, is set to reveal more information about its experimental gene therapy for the condition Tuesday.
Elsewhere, Pfizer recently began dosing its own microdystrophin gene therapy candidate in a Phase 1b study. Picked up in the pharma giant's 2016 acquisition of Bamboo Therapeutics, the experimental treatment also uses an AAV9 vector as a delivery platform.
Solid had been set to report data around the same time as Pfizer, but the delay caused by its clinical hold means Pfizer will get first billing come 2019.