Edgewise Therapeutics, Inc. announced positive 12-month topline results from the ongoing ARCH study, an open label, single-center study assessing the safety, tolerability, impact on muscle damage biomarkers, and pharmacokinetics (PK) of EDG-5506 in adults with BMD. EDG-5506 is an orally administered small molecule designed to prevent contraction-induced muscle damage in dystrophinopathies including BMD and Duchenne muscular dystrophy (DMD). The ARCH study is evaluating varying doses of EDG-5506 administered daily over 24 months in 12 adults with BMD.

The Company is reporting data at the end of 12 months of treatment with EDG-5506. EDG-5506 was well-tolerated in all participants with no discontinuations or dose reductions due to adverse events. Consistent with prior observations, treatment with EDG-5506 led to significant decreases in key biomarkers of muscle damage.

Importantly, CK and TNNI2 were reduced by an average of 37% (p=0.001) and 79% (p<0.0001) from baseline, respectively, at the participants 12-month visit. After 12 months of EDG-5506 dosing, NSAA scores continued to trend in a positive direction. Nine of the twelve participants showed either a functional improvement (n=6) or exhibited stable disease (n=3) on NSAA relative to their baselines.

NSAA scores show a consistent positive trend that diverges from trajectories observed in the natural history studies reported by Bello et al. (2016) and van de Velde et al. (2021) in which the yearly decline was -1.2 NSAA points. Overall, one-year functional results were observed to have a +0.4-point improvement on the NSAA compared to the -1.2-point anticipated natural history decline in a population of BMD patients predicted to have a relentless course of disease progression. The positive results from the 12-month ARCH study support the hypothesis that a reduction in contraction-induced muscle damage in muscular dystrophies, associated with EDG-5506 administration, has the potential to preserve and improve muscle function while preventing disease progression in dystrophinopathies.

Observations from ARCH identified key factors, including the optimal dosing strategy of EDG-5506, for the design of a potentially registrational trial. A pivotal cohort, GRAND CANYON, has been added to the CANYON study and is anticipated to begin enrollment in the third quarter of 2023.