LB: DAYLIGHT, a phase 2 study of fordadistrogene movaparvovec in participants with early-stage Duchenne muscular dystrophy

Topic:

Clinical Trials

Poster Number: T425

Author(s):

Barry Byrne, MD, PhD, University of Florida, Kristi Jones, MD, PhD, University of Sydney, Ian Woodcock, MD, The Royal Children’s Hospital, Barbara Gatti, MD, Pfizer, Inc., Qi Shen, MD, PhD, Pfizer, Inc., Benjamin Maligalig, MPH, Pfizer, Inc., Codrin Lungu, MD, Pfizer, Inc., Francesco Muntoni, MD, Great Ormond Street Institute of Child Health

Background:
Fordadistrogene movaparvovec (FM) is a recombinant AAV9-based gene therapy developed as a disease-modifying treatment for Duchene muscular dystrophy (DMD), that will potentially halt disease progression and improve motor function. The DAYLIGHT study will assess the safety and dystrophin expression of FM in participants with early-stage DMD.

Study Design and Methods:
DAYLIGHT is a phase 2, multicenter, single-arm, open-label study.
The primary endpoints through week 52 are the incidence and severity of treatment-emergent adverse events and serious adverse events, incidence and magnitude of abnormal laboratory findings, and incidence of abnormal and clinically relevant changes in neurological examinations, weight, vital signs, cardiac troponin I, electrocardiogram, and echocardiography. Secondary endpoints are expression and distribution of muscle mini-dystrophin at weeks 9, 52, and year 5, and safety outcomes through 5 years. Exploratory endpoints include immune responses to mini-dystrophin and the AAV9 capsid, change in serum creatine kinase concentration through 5 years, functional assessments, and health-related quality of life. Inclusion criteria are age ≥2 to <4 years at screening and confirmed genetic diagnosis of DMD. Exclusion criteria include any mutation affecting any exon between 9-13 inclusive, a deletion that affects exons 29 and 30, or a deletion affecting any exon between 56-71 inclusive, known contraindication to eculizumab, cardiac pathology eg myocarditis, prior gene therapy treatment, prior or current glucocorticoid treatment, and positive test for neutralizing antibodies to AAV9.

Results:
Ten participants were enrolled at 5 sites in the US and Australia and received a single infusion of FM (2E14 vg/kg). Three participants were in the US and 7 in Australia. Mean (range) age at screening was 2.7 (2-4) years. Nine participants had exon mutations and 1 participant had a splice-site mutation.
Conclusions: DAYLIGHT aims to assess the safety and mini-dystrophin expression of FM in participants with DMD aged ≥2 to <4 years, prior to the development of significant muscle damage. As FM is designed to provide a functional form of dystrophin, it is hypothesized to have clinically meaningful benefits in participants with early DMD. This study was funded by Pfizer. ClinicalTrials.gov: NCT05429372.