Cardiac safety of fordadistrogene movaparvovec gene therapy in Duchenne muscular dystrophy: Initial observations from a phase 1b trial.

Fordadistrogene movaparvovec (FM; PF-06939926) is a recombinant adeno-associated virus serotype-9 gene-replacement construct containing a mini-dystrophin transgene in development for Duchenne muscular dystrophy (DMD). We present findings of cardiac safety assessments in participants with DMD during a 1-year follow-up from an ongoing phase 1b multicenter, single-arm, open-label trial of low- and high-dose FM. Cardiac troponin-I (cTn-I) levels and cardiac magnetic resonance imaging measures were obtained from 19 ambulatory participants (n = 3, low dose; n = 16, high dose; median age 8.8 years) and 3 non-ambulatory participants (high dose; median age 15.1 years). Six ambulatory and 3 non-ambulatory participants had cTn-I levels above the upper limit of normal at baseline. Of these, 1 ambulatory participant and 2 non-ambulatory participants had cTn-I levels >3× the baseline level during the first year following infusion. At 1 year post-infusion, mean (±SD) changes from baseline in left ventricular ejection fraction (LVEF) were -0.9% ± 4.0% in ambulatory participants and -3.1% ± 1.8% in non-ambulatory participants. One 16-year-old non-ambulatory participant with DMD experienced fatal cardiogenic shock 6 days after a high dose of FM. With the exception of participants with DMD with advanced cardiac fibrosis, assessments of cTn-I, LVEF by cardiac magnetic resonance imaging and progression of late gadolinium enhancement suggest low cardiac toxicity from FM in ambulatory participants with DMD in this study. ClinicalTrials.gov identifier: NCT03362502.