The investigational therapy edasalonexent was seen to slow disease progression in boys with Duchenne muscular dystrophy, almost one-year results from the MoveDMD trial report.
Specifically, edasalonexent — administered orally as 100 mg/kg dose for 48 weeks — resulted in a statistically significant delay in disease progression and signs of lower inflammation and muscle fat accumulation compared to measures taken before the start of treatment.
A pivotal Phase 3 study of this potential therapy — designed to treat all DMD patients — is being planned.
These results were shared at the American Academy of Neurology 70th Annual meeting in a presentation titled “MoveDMD: Positive Effects of Edasalonexent, an NF-κB Inhibitor, in 4 to 7-Year Old Patients with Duchenne Muscular Dystrophy in Phase 2 Study with an Open-Label Extension.”
Edasalonexent, being developed by Catabasis Pharmaceuticals, is a small molecule design to inhibit a protein called NF-κB that promotes muscle damage in DMD and prevents muscle regeneration. It is being developed as a potential disease-modifying therapy for all DMD patients, regardless of their underlying disease-causing mutation.
The Phase 1/2 MoveDMD (NCT02439216) trial enrolled 31 DMD patients, ages 4 to 7, with different dystrophin mutations. All were naïve for steroid therapy, meaning they had never received such treatment. In the study’s second phase, the boys were randomized to receive either 67 or 100 mg/kg/day of edasalonexent, or a placebo, for up to 60 weeks of treatment. (Phase 1 was an open-label and dose-escalating study.)
The analysis included 23 patients who underwent tests prior to starting treatment for a mean of 39 weeks, serving an off-treatment control period to assess differences in outcomes compared to periods on treatment.
Researchers used both magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to measure efficacy. MRI is a non-invasive approach to assess disease progression. MRI T2 weighted image (MRI T2) is capable of measuring both inflammation and fat content in patient’s muscles. MRS T2 imaging measures inflammation and MRS fat fraction assesses fat accumulation in the muscle.
With age, DMD patients experience an increase in fat in their muscles with consequent loss of functional abilities.
Results showed that patients given edasalonexent at the higher, 100 mg/kg, dose had statistically significant improvements in both inflammation and fat content in the lower leg compared to the off-treatment control period. Changes were significant after 12 weeks of treatment, and maintained thereafter — at 24, 36, and 48 weeks of treatment.
While patients during the off-treatment control period showed a fat content increase averaging 2.6 percent per year in the soleus muscle (the muscle located at the back part of the lower leg), the average fat content increase recorded during the 48 weeks of treatment with 100 mg/kg of edasalonexent was 0.85 percent.
In contrast, data from the ImagingDMD natural history study showed that boys treated with steroids had an average increase of 3 percent per year.
At 100 mg/kg, 48 weeks of edasalonexent treatment also resulted in significant improvements in the fat fraction of the vastus lateralis (VL), part of the quadriceps muscle — an annual 5.9 percent increase, compared to a 10.4 percent in the same boys during the off-treatment period. Boys from the ImagingDMD natural history study had a 7 percent increase per year.
Almost one year of higher-dose treatment also led to improvements in all measures of muscle function analyzed, including in the North Star Ambulatory Assessment (NSAA) and tests such as the 10-meter walk/run, 4-stair climb, and time to stand.
Edasalonexent was found to be well-tolerated, with no safety signals reported in the trial.
“The results reported to date from the MoveDMD trial have been consistent and support edasalonexent as a disease-modifying therapy. Overall, in the MoveDMD trial edasalonexent has slowed progression of this disease based on improvements in multiple assessments of physical function and biomarkers of muscle health and inflammation,” Jill C. Milne, PhD, chief executive officer of Catabasis, said in a press release.
“We believe that these effects ultimately will translate to boys with Duchenne maintaining functional abilities longer,” Milne added.
Based on these positive findings, Catabasis is planning a 12-month Phase 3 study to further assess the safety and efficacy of edasalonexent.
“I am very encouraged to see these emerging data with favorable MRI changes and results of muscle function assessments with edasalonexent, which are clearly divergent from the untreated disease progression that I see in boys in this age range with Duchenne,” said Richard Finkel, MD, chief, division of Neurology, department of Pediatrics at Nemours Children’s Hospital, Orlando, and a principal study investigator.
“There is a strong need for a therapy with a safety and tolerability profile like edasalonexent for the many boys affected by this devastating disease,” Finkel concluded.