EDG-5506 Shows Promise at Reducing Becker MD Muscle Damage
6-month interim data results also show improved physical function in patients
EDG-5506, Edgewise Therapeutics’ experimental oral therapy, continues to safely reduce muscle damage and improve physical function in adults with Becker muscular dystrophy (BMD), according to six-month interim data from the Phase 1 ARCH trial.
Treatment led to a marked reduction in the average levels of key markers of muscle damage relative to the trial’s start and motor function continues to tend to improve compared to the typical decline seen in untreated patients.
“BMD is a serious neuromuscular disorder and individuals living with this disease have no approved treatment options,” Kevin Koch, PhD, Edgewise’s president and CEO, said in a company press release. “These early data are very encouraging and highlight EDG-5506’s potential to alter the course of the disease.”
The Phase 1 findings were presented by Joanne Donovan, MD, PhD, Edgewise’s chief medical officer, in a session called “Targeting Fast Muscle Myosin: a Novel Approach to Protecting Muscle for the Dystrophinopathies,” Oct. 14, as part of the 2022 Annual Congress of the World Muscle Society. The presentation was titled “Clinical Development of EDG-5506 in Duchenne and Becker Muscular Dystrophy.”
A placebo-controlled Phase 2 trial called CANYON (NCT05291091) is testing EDG-5506 in up to 66 boys and men with BMD and the study is enrolling male patients, ages 12–50, at six sites in the U.S.
EDG-5506 is being developed as a potential disease-modifying therapy for dystrophinopathies, neuromuscular conditions caused by mutations in the DMD gene that include BMD and the more severe Duchenne muscular dystrophy (DMD).
The DMD gene contains the information to produce dystrophin, a protein that helps protect muscle cells from being damaged during movement. In BMD and DMD, muscle cells become more susceptible to wear and tear from contractions.
EDG-5506 is a small orally available molecule designed to protect muscle fibers from the use-driven damage and scar tissue buildup that lead to muscle weakness and wasting. It works by suppressing myosin, a protein involved in muscle contraction.
The ongoing, open-label Phase 1 ARCH clinical trial (NCT05160415) was designed to assess EDG-5506’s one-year safety and pharmacokinetics, or its movement into, through, and out of the body. Changes in muscle damage biomarker levels, physical function measures, timed tests, and patient-reported outcomes are also being evaluated.
A total of 12 men with BMD (mean age, 32.8) who were able to walk independently were enrolled. Seven had previously participated in a brief Phase 1 trial (NCT04585464), which indicated EDG-5506 at a daily dose of 20 mg rapidly reduced markers of muscle damage.
Interim trial data promising for EDG-5506
In the ARCH study, participants started at a daily dose of 10 mg at night for the first two months, which was followed by a 15 mg daily dose for the next four months. After completing six months of treatment, all have started to receive 20 mg per night.
Consistent with the trial’s four-month data, the therapy continues to be well tolerated after six months, with no dose reductions or treatment discontinuations reported. The most commonly reported side effects have been dizziness, drowsiness, and headache.
Target circulating levels of EDG-5506 were reached after the dose was increased to 15 mg.
At the most recent assessment, the average levels of two muscle damage markers, fast skeletal muscle troponin I and creatine kinase (CK), were significantly reduced. Fast skeletal muscle troponin I levels were reduced by 75% and average CK levels were reduced by 39%.
Men with the highest values at the start of the study showed the greatest reductions, supporting “protection against activity-induced damage.”
Also, the molecular signature of BMD identified in these patients is progressively being reverted with EDG-5506 treatment. The levels of these proteins, many involved in inflammation, have shown a significant drop since the start of the study.
Gains in motor function
Motor function also continued to show an improvement trend, with eight patients improving or stabilizing relative to the study’s start on the North Star Ambulatory Assessment (NSAA), a measure of motor function with muscular dystrophy.
Contrary to the 1.22-point annual decline in NSAA scores reported for untreated BMD patients participating in a natural history study, those treated with EDG-5506 for six months show a consistent, positive trend toward increase, reflecting better function.
A similar positive trend was seen for the North Star Assessment for Limb Girdle Type Muscular Dystrophies (NSAD) scores, a scale developed for adult patients that features tasks of increasing difficulty.
Six months of EDG-5506 treatment was also associated with a reduction in patient-reported pain scores relative to the study’s start, while “other patient-reported outcomes, such as mental health, fatigue and sleep, also trended better,” Donovan noted in the presentation.
These findings support EDG-5506’s effectiveness in reducing contraction-induced damage and in helping preserve and improve muscle function in dystrophinopathies.
“As a company, we are dedicated to the muscular dystrophy community and are thankful for the trial participants as we are critically evaluating this important data to help guide our clinical development plan in BMD and DMD,” Donovan said in the release. “We continue to be encouraged by EDG-5506’s safety profile and the positive trends observed with these interim data.”
Edgewise plans to launch a Phase 2 trial, called LYNX (NCT05540860), to evaluate the safety, pharmacokinetics, and effects on muscle damage biomarkers of EDG-5506 against a placebo in up to 27 boys with DMD. The study is expected to start this year and contact information has been made available.
The company, along with the Virginia Commonwealth University, initiated an international natural history study (NCT05257473) to follow about 150 male BMD patients, ages 8 and up, in the absence of treatment. Contact and location information is also available for that.
The goal of the study is to assess the natural course of the disease, which may help evaluate the effectiveness of therapies such as EDG-5506.