2-year EDG-5506 treatment helps preserve motor function in BMD

Edgewise releases top-line results from Phase 1 ARCH trial

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by Andrea Lobo |

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Oral treatment with EDG-5506, now known as sevasemten, continued to stabilize muscle function after two years in men with Becker muscular dystrophy (BMD) taking part in a Phase 1 trial.

That’s in contrast to the progressive deterioration of motor function seen during the natural course of BMD in the absence of treatment.

According to Edgewise Therapeutics, the therapy’s developer, the daily regimen used in the Phase 1 ARCH trial (NCT05160415) was generally well tolerated and reduced markers of muscle damage.

“We are pleased by the promising and consistent functional results observed over two years of treatment with sevasemten, together with the favorable safety and tolerability profile,” Joanne Donovan, MD, PhD, Edgewise’s chief medical officer, said in a company press release.

The top-line ARCH results were presented at the American Academy of Neurology’s 2024 annual meeting in Denver.

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EDG-5506 blocks protein to ease movements

BMD is caused by mutations in the DMD gene that result in low or defective production of the dystrophin protein. Dystrophin functions as a shock absorber in muscle cells, supporting them during muscle contractions. The shortage of working dystrophin causes progressive muscle damage and loss of motor function.

Sevasemten is a small molecule designed to block the activity of myosin, a key protein involved in muscle contractions. The treatment is expected to make muscle movements more gentle, protecting the muscles from damage.

The completed ARCH trial enrolled 12 men with BMD who were able to walk. Participants started at a 10 mg daily dose for the first two months, followed by a 15 mg daily dose for the next four months. At six months, they started receiving a 20 mg dose, which was reduced to 10 mg after 15 months of treatment, and continued up to 24 months.

Top-line reports showed that there were no treatment discontinuations or dose reductions due to side effects.

Moreover, consistent with reported data at one year of treatment, sevasemten significantly decreased levels of key biomarkers of muscle damage, including creatine kinase, fast skeletal muscle troponin I (TNNI2), and myoglobin.

Physical function was evaluated using the North Star Ambulatory Assessment, a standard way to evaluate motor abilities. Natural BMD history studies show that NSAA scores usually decrease (worsen) by an average of 2.4 points per year.

In contrast, average NSAA scores for sevasemten-treated patients improved by 0.2 points after two years of treatment. Results of hand grip strength tests and the 100-meter timed test of maximal performance were unchanged relative to ARCH start.

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The company said the results support the hypothesis that a reduction of contraction-related muscle damage can preserve motor function and stop disease progression in BMD patients.

“In my experience, each one-point decrease in NSAA represents a loss of function important to daily activities,” said Barry J. Byrne, MD, PhD, director of the Powell Gene Therapy Center at University of Florida and chief medical advisor at the Muscular Dystrophy Association. “I have been closely following the progress of sevasemten in the clinic and am encouraged by the two-year results and the potential of this novel muscle-targeted therapy for individuals with Becker.”

The pharmacological properties of sevasemten support the use of a 10 mg dose in the ongoing GRAND CANYON group of about 120 participants with BMD that follows the Phase 2 CANYON trial (NCT05291091). The trial is currently recruiting patients at sites across the U.S., the Netherlands, and the U.K.

GRAND CANYON will assess sevasemten’s safety and pharmacological properties, as well as muscle damage biomarkers and functional measures. If positive, results from this trial could support applications seeking regulatory approval.

The company discussed the ARCH data on a webcast Tuesday, April 16. A replay and slide presentation are available.

A community webinar will be held on May 13 at 1 p.m. EDT to discuss data from ARCH and the GRAND CANYON study.