EDG-5506 helping to preserve muscles in Becker MD Phase 1 trial

Oral therapy now in enlarging, possibly pivotal Phase 2 study

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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An illustrated graph showing measured improvements in a clinical trial.

After a year of treatment with the experimental oral therapy EDG-5506 in a Phase 1 study, most men with Becker muscular dystrophy (BMD) show stable or improved motor function — a marked contrast to the disease’s natural course, where motor function worsens over time.

One-year findings in the ongoing Phase 1 ARCH clinical trial (NCT05160415) also support EDG-5506 being generally well tolerated and reducing markers of muscle damage, according to the therapy’s developer, Edgewise Therapeutics.

“We are quite pleased by the robust and consistent results observed at 12 months with EDG 5506 treatment, which, together with the favorable safety/tolerability profile, are highly encouraging,” Joanne Donovan, MD, PhD, Edgewise’s chief medical officer, said in a company press release.

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Based on these Phase 1 findings, Edgewise will expand the ongoing Phase 2 CANYON trial (NCT05291091) that is testing various doses of EDG-5506 against a placebo in about 50 children and adults with BMD, ages 12 to 50. The trial will add a pivotal “GRAND CANYON” cohort of about 120 BMD patients that, if results are positive, could support applications for the therapy’s approval.

“These data have allowed us to quickly pivot our CANYON study to include a potentially registration-enabling cohort,” Donovan said.

Patient enrollment in CANYON is continuing at sites across the U.S., and in the Netherlands and the U.K. Recruitment for a GRAND CANYON patient group is expected to begin either later this summer or in early autumn.

BMD is caused by mutations that affect the muscle protein dystrophin. Normally, dystrophin acts like a ‘shock absorber’ in muscle cells, helping to cushion and support the cell’s structures during muscle contractions. In BMD, as well as Duchenne muscular dystrophy (DMD), the lack of working dystrophin causes muscles to acquire damage over time, ultimately leading to the progressive loss of physical function that characterizes the disease.

EDG-5506 is designed to block the activity of myosin, a protein that’s involved in muscle contraction. The basic idea behind the therapy is to prevent contraction damage to muscles due to low or absent dystrophin.

“Becker is a devastating, neuromuscular disease which currently has no approved therapies. In my experience, once symptoms of muscle weakness occur, muscle has already been lost. Once declining, individuals with Becker have a relentless course of disease progression,” said Craig McDonald, MD, a professor in the department of physical medicine and rehabilitation at the University of California Davis.

ARCH trial reports significantly lower muscle damage markers with EDG-5506

ARCH enrolled 12 men with BMD, all able to walk, who are being treated daily with oral EDG-5506 for two years. The trial is due to conclude in April 2024.

The study’s main goals are to assess the safety of the experimental therapy, and Edgewise reports that results to date are generally positive: the therapy has been well tolerated overall, with no patients stopping the treatment or reducing its dose due to side effects.

Consistent with previously announced interim data, one year of EDG-5506 treatment was seen to significantly lower markers of muscle damage, the company reported. Specifically, levels of creatine kinase (CK) fell by an average of 37%, while levels of fast skeletal muscle troponin I (TNNI2) were reduced by 79% on average, the company reported.

Over the course of the study, participants’ physical function routinely is measured using the North Star Ambulatory Assessment (NSAA). Prior natural history studies have suggested that, in the absence of treatment, NSAA scores usually decrease (worsen) by an average of 1.2 points each year for adults with BMD.

In contrast, average NSAA scores for ARCH patients rose by 0.4 points after one year of treatment. Specifically, nine of its 12 participants maintained or improved their NSAA scores after one year of treatment compared with baseline (study start) measures. The other three participants experienced some loss of motor function, as measured by NSAA scores.

These data collectively “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” BMD and DMD, Edgewise stated.

“I have been closely following the progress of EDG-5506 in the clinic and am excited by the 12-month results and EDG-5506’s potential as a novel therapy for individuals with Becker,” McDonald said.

EDG-5506 also is being developed to treat Duchenne MD, and the Phase 2 LYNX clinical trial (NCT05540860) currently is enrolling boys with DMD, ages 4 to 9, at multiple centers in the U.S. The yearlong trial’s initial three months includes a placebo patient group, followed by an open-label study where all enrolled will be treated for 40 weeks.