A clinical study shows the tolerance and safety of an experimental drug in boys with DMD

Targeted drugs NF-κB, a key link between dystrophin loss and disease progression, and could benefit all patients with DMD regardless of the genetic mutation, according to research published in the Journal of Neuromuscular Diseases

Patients with Duchenne muscular dystrophy (DMD) have few treatment options. Currently available or under development drugs target only a subset of DMD patients with a particular genetic mutation or cause significant adverse effects. The experimental drug edasalonexent, an oral NF-oralκInhibitor B, has the potential to slow the progression of the disease for all patients with DMD. The results of a Phase I clinical trial published in the Journal of Neuromuscular Diseases indicate that the drug has been well tolerated without any safety concerns in boys with DMD, paving the way for further clinical trials.

"In addition to being well tolerated in pediatric patients with DMD, our Phase 1 data showed that edasalonexent (CAT-1004) inhibitedκB. This is important because NF-κB is a key link between the loss of dystrophin and the progression of DMD-related disease. This would mean that edasalonexent could potentially limit the progression of the disease in all patients with DMD, regardless of their underlying mutation, "says Joanne Donovan, MD, Ph.D., Chief Medical Officer of Catabasis Pharmaceuticals. , Inc. (Cambridge, Mbad., USA).

Edasalonexent is an orally administered small molecule that contains two active ingredients, salicylic acid and docosahexaenoic acid (DHA), an omega-3 fatty acid, which are linked together to produce a single molecule. These two molecules are inhibitors of NF-kB, but edasalonexent inhibits NF-kB much more potently than either of the basic molecules alone.

In a previous study, edasalonexent was well tolerated and absorbed by adults and inhibited NF.κB. The purpose of this study, a Phase 1/2 study called MoveDMD, was to evaluate the effects on children with DMD. In this open-label, multi-dose, phase 1 clinical trial, 17 boys (mean age 5.5 years) received three sequential increasing doses of edasalonexent (33, 67, and 100 years). mg / kg / day). All doses were well tolerated, with no serious adverse events, no interruption of treatment, no dose reduction or discontinuation of treatment due to adverse effects. Most side effects were mild and gastrointestinal.

Importantly, for the two highest doses (67 and 100 mg / kg / day), seven days of treatment resulted in a decrease in NF levels.κB-regulated genes, as measured by sequencing mRNA in whole blood. The treatment also reduced serum protein levels thought to come from damaged muscles. "This shows that with a short-term dosage, edasalonexent can directly reduce NF-elevated levels.κB in circulating DMD mononuclear cells before any observable change in the muscles, "notes Dr. Donovan.

Because of the potential universal benefits of edasalonexent for all types of DMD, Dr. Donovan suggests that it could be used alone or in combination with other drugs, including gene therapy approaches in development course. Edasalonexent can potentially reduce muscle inflammation and degeneration and improve muscle regeneration. She also suggests that inhibition of NFκB can have modifying effects of the disease.

"The data from the Phase 1 MoveDMD clinical trial reinforces the good safety and safety profile of edasalonexent that we also observed in the Phase 2 and Phase 2 trial. open-label extension, "adds Erika Finanger, MD, badociate professor of pediatrics, Division of Neurology, School of Medicine at Oregon Health & Science University, and lead investigator for the MoveD® and PolarisD® trials. "I am pleased to continue to evaluate edasalonexent as a potential new treatment for people affected by Duchenne, and I am excited to participate in the Phase 3 Polaris DMD study."

DMD is the most common genetic neuromuscular disease affecting one in 3,500 to 6,000 male births. The disease is characterized by progressive muscle weakness and degeneration accompanied by a loss of contractibility. It is caused by one of the many mutations of the DMD gene. Regardless of the mutation considered, chronic activation of the transcription factor NF- is a key factor in muscle degeneration and suppression of muscle regeneration in DMD.κB, which causes the loss of dystrophin, a protein that helps keep muscle cells intact.