Shares in Solid Biosciences dropped as much as 71% on Tuesday after it said the FDA placed a clinical hold on the Phase I/II IGNITE DMD study of SGT-001, an adeno-associated viral vector-mediated gene transfer under investigation for Duchenne muscular dystrophy (DMD). The company noted that the move comes after a patient dosed in late October experienced a serious adverse event (SAE) deemed related to SGT-001 that was characterised by complement activation, thrombocytopaenia, acute kidney injury and cardio-pulmonary insufficiency.
According to Solid Biosciences, six patients have been administered SGT-001 in the trial, including three subjects in the first cohort at a dose of 5E13 vg/kg and three participants in the second cohort at a 2E14 vg/kg dose. The SAE occurred in the third patient dosed in the second cohort. "Neither cytokine- nor coagulopathy-related abnormalities were observed," the company stated, adding that the patient is "recovering and continues to improve."
CEO Ilan Ganot indicated that "in the coming weeks, we anticipate that we will have a better understanding of the biological activity and potential benefit of SGT-001." Solid Biosciences said it plans to work with the FDA to resolve the clinical hold and determine next steps for the IGNITE DMD study, from which additional biomarker data are anticipated before year end.
In June last year, the FDA lifted another clinical hold that had been placed on the study after the first patient administered SGT-001 was hospitalised due to laboratory findings that showed lower platelet and red blood cell counts, as well as evidence of complement activation. At the time, the company noted that it had made changes to the trial's protocol, including the addition of intravenous glucocorticoids in the initial weeks following administration of SGT-001 and enhanced monitoring measures that include a panel for complement activation.
Commenting on the news, SVB Leerink analyst Joseph Schwartz suggested the new adverse event resembles the one that prompted the first clinical hold last year. "The safety profile of SGT-001 will most likely be under increased scrutiny," he added.
The latest setback for Solid Biosciences comes shortly after Pfizer disclosed that two patients treated in a Phase Ib study of its investigational DMD gene therapy PF-06939926 were hospitalised due to adverse events, with one subject suffering from kidney injury, haemolysis and reduced platelet count. Meanwhile, in August, shares in Sarepta Therapeutics fell after a case of rhabdomyolysis was reported in a boy treated with the drugmaker's investigational micro-dystrophin gene therapy for DMD, SRP-9001, although the company said the event had been "erroneously submitted" to the FDA's adverse event reporting system.
Meanwhile, RBC Capital Markets analyst Brian Abrahams pointed to the fact that Sarepta has dosed at least 16 patients so far with no clinical holds, indicating a probable superior safety profile for its therapy. He predicted that SRP-9001 will win sole approval and ultimately generate revenues of $4 billion globally. Sarepta's already FDA-approved DMD therapy Exondys 51 (eteplirsen) brought in total sales of $301 million in 2018.
For related analysis, read ViewPoints: Pfizer DMD update leaves Sarepta in top spot- and with its pick of the patients, and see ViewPoints: Sarepta takes the gloves off over DMD safety disclosure.
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