by: Parent Project Muscular Dystrophy
Edgewise Therapeutics, Inc. announced today positive topline results from the Multiple Ascending Dose (MAD) portion of a first-in-human Phase 1 clinical trial assessing the safety and tolerability of escalating doses of EDG-5506, an orally administered small molecule myosin inhibitor designed to protect injury-susceptible fast skeletal muscle fibers in dystrophinopathies such as DMD and BMD.
In addition to safety, the goal in the MAD study was to derive a relationship between dose, muscle exposure and involuntary twitch force inhibition, a surrogate for EDG-5506’s novel mechanism of action. EDG-5506 was shown to be generally well tolerated at all doses studied in healthy volunteers with no adverse events seen in laboratory values, electrocardiograms, or other vital signs.
Importantly, dosing with EDG-5506 was not found to affect voluntary grip, shoulder, or hip strength and there was no negative impact observed on alternate forms of myosin elsewhere in the body (e.g., cardiac). These compelling observations provide preliminary evidence of a dose dependent, selective inhibition of fast skeletal muscle fibers following multiple doses of EDG-5506.
Based on these favorable results, Edgewise anticipates initiation of Phase 2 trials in individuals with BMD in the first half of 2022 and DMD in the second half of 2022. Moreover, Edgewise has also started dosing individuals with BMD as part of the ongoing Phase 1b clinical trial, with plans to enroll approximately 8 subjects to assess a 20 mg dose of EDG-5506 or placebo for 14 days. Safety, PK and changes to biomarkers of muscle damage, will be evaluated for the first time in Becker patients. Edgewise also expects to initiate a follow-on open-label study in BMD patients in the first quarter of 2022.
About EDG-5506 for DMD and BMD
EDG-5506 is an orally administered small molecule designed to address the root cause of dystrophinopathies including DMD and BMD. EDG-5506 presents a novel mechanism of action to selectively limit injurious hypercontraction stress caused by the absence of functional dystrophin. EDG-5506 has the potential to benefit a broad range of patients suffering from debilitating rare neuromuscular disorders. It is anticipated to be used as a single agent therapy but it may also provide a synergistic or additive effect in combination with available therapies and therapies currently in development.
The Phase 1 study of EDG-5506 is designed to evaluate safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) in adult healthy volunteers (Phase 1a) and in adults with BMD (Phase 1b). EDG-5506 is advancing in the Multiple Ascending Dose (MAD) portion of the study. The Company expects to have topline MAD data in healthy volunteers and in individuals with BMD later in 2021. Go to clinicaltrials.gov to learn more about this study (NCT04585464).
