CHARLOTTE, N.C. – presented at the annual meeting of the Child Neurology Society.
The NF-kB pathway is “fundamental to the pathogenesis and biology of DMD,” said, chief of neurology at Nemours Children’s Health System in Orlando and principal investigator for the phase 2 study, known as .
A lack of dystrophin, combined with the mechanical stress of muscle contraction, activates the NF-kB pathway and inhibits muscle regeneration. “It is known that there is inflammation and fibrosis and release of cytokines early in life” in patients with DMD, Dr. Finkel said.
Independent of mutation
Edasalonexent is an NF-kB inhibitor that is being developed byas a therapy for patients with DMD regardless of the genetic mutation that is causing the disease. It may be used as monotherapy or with other dystrophin-targeted treatments, Dr. Finkel said.
In a mouse model of DMD, an analog of the drug reduced muscle inflammation and increased the force of diaphragm muscle. To assess edasalonexent’s safety, pharmacokinetics, and effects on functional measures and MRI in patients with DMD, Dr. Finkel and colleagues conducted the MoveDMD trial. Investigators enrolled boys aged 4 years to younger than 8 years who were not receiving treatment with corticosteroids.
Researchers first examined drug safety and pharmacokinetics in 17 boys who received the treatment for 1 week. The investigators then followed 16 of these patients off treatment for as long as 6 months. This off-treatment period was followed by a phase 2, placebo-controlled period, during which the 16 patients and another 15 patients received edasalonexent 67 mg/kg/day, edasalonexent 100 mg/kg/day, or placebo for 12 weeks. Patients subsequently entered an open-label extension study.
Dr. Finkel presented a comparison of outcomes during the off-treatment period with outcomes during the open-label extension. “We used these boys as their own internal control, if you wish,” he said.
Creatine kinase levels decreased soon after treatment, as did other markers of muscle disease. The drug “seems to have an early and sustained biomarker response,” Dr. Finkel said.
Annualized rate of change on lower leg muscle MRI-T2 decreased. “There is a relative reduction and stabilization from week 12 all the way out through the open-label extension to 72 weeks,” he said. “It suggests that there is an early and sustained response in stabilization of the MRI as a biomarker.”
Timed function tests
A comparison of the annualized rates of change on timed function tests – including the 10-meter walk/run, time-to-stand, and four-stair-climb, and the North Star Ambulatory Assessment – during the off-treatment and on-treatment periods indicated slowing of disease progression with treatment. “Shortly after starting on drug ... there was a relative stabilization in each of these measures,” Dr. Finkel said.