Cardiac safety of fordadistrogene movaparvovec in Duchenne muscular dystrophy after 3 years follow-up from a phase 1b trial


Clinical Trials

Poster Number: M179


Sarah Sherlock, PhD, Pfizer Inc, Codrin Lungu, MD, Pfizer Inc, Daniel Levy, MD-PhD, Pfizer, Perry Shieh, MD, PhD, University of California Los Angeles, Edward Smith, MD, Duke University, Kelly Ryan, BSN, MS, Pfizer Inc, Russell Butterfield, MD, PhD, University of Utah, Avery McIntosh, PhD, Pfizer Inc, Qi Shen, MD, Pfizer

Fordadistrogene movaparvovec is an adeno-associated virus serotype-9 (AAV9) gene-replacement construct containing a mini-dystrophin transgene, in development for Duchenne muscular dystrophy (DMD). Cardiac dysfunction is a key component of disease progression.

We present findings of cardiac MRI safety assessments in ambulatory DMD participants during a 3-year follow-up from an ongoing, phase 1b, multicenter, single-arm, open-label trial of low- and high-dose fordadistrogene movaparvovec. Left ventricular ejection fraction (LVEF) and presence of late gadolinium enhancement (LGE) were assessed over a 3-year monitoring period.

Nineteen ambulatory participants with DMD received a single infusion of fordadistrogene movaparvovec; 3 participants received a low-dose and 16 were administered a high-dose. Cardiac MRI data was captured for 17 participants (3 low-dose and 14 high-dose) at baseline, 1 year and 2 years post-infusion. 3-year post-infusion cardiac MRI data was available for 10 participants (2 low-dose and 8 high-dose). Baseline LVEF measures were similar between low-dose and high-dose participants with mean (±SD) of 56.9±1.8% and 57.8±2.1%, respectively. Change from baseline (CFB) in LVEF across participants was -0.9±4.0% after 1 year, -2.6±3.8% after 2 years and -5.1±3.6% after 3 years. At baseline, participants who received gadolinium were recorded as LGE-positive (n=7) or LGE-negative (n=7). Of the 7 initially LGE-negative participants there were no new LGE-positive participants after 1 year, and two new LGE-positive participants after 2 years.

Natural history studies suggest LVEF declines in DMD patients at a rate of ~1.6% per year. Study participants who received a single infusion of fordadistrogene movaparvovec showed LVEF declines consistent with natural history. Appearance of new LGE signal is expected during typical DMD progression and our findings appear consistent with this natural course. Overall, these data provide additional confidence in the long-term cardiac safety profile fordadistrogene movaparvovec.