U-M startup marks milestone in drug therapy for boys with Duchenne muscular dystrophy

10/13/2017

Two boys under treatment outside the United States for Duchenne muscular dystrophy—an X-linked disease that affects only boys and young men—met key milestones while on Carmeseal-MD, a drug developed by a University of Michigan startup.

Phrixus Pharmaceuticals Inc. is working with Ethicor Pharma Ltd., its licensor, to commercialize the drug outside the U.S. with plans to begin the first trial of Carmeseal-MD at Cincinnati Children’s Hospital in the first quarter 2018.

The drug’s active ingredient, P-188 NF, was developed by Joseph Metzger while a professor of molecular and integrative physiology at U-M. Metzger, now chair of the Department of Integrative Biology and Physiology at the University of Minnesota, has shown that P-188 NF could boost the blood-pumping capacity of damaged hearts by binding to the damaged regions of cell membranes.

When P-188 NF, which Metzger and his colleagues called a “molecular band-aid,” is infused into the bloodstream, it finds and attaches to microscopic instabilities and tears in the heart muscle. This can prevent the damaging pathological leakage of calcium into the heart cells and improve the heart’s ability to provide sufficient oxygen to the vital organs.

The drug is being prescribed to boys and young men outside the U.S. who have both respiratory and cardiac disease. The longest treatment so far has been for 15 months without apparent adverse events, but with significant reductions in biomarkers of damage to skeletal and heart muscle.

“It’s a progressive and lethal disease,” said Thomas A. Collet, president and CEO of Phrixus. “This is one of the most prevalent of the rare diseases and no treatment is fully approved for the numerous negative consequences of the disease.”

Duchenne muscular dystrophy affects roughly 15,000 to 20,000 boys in the U.S. and Europe each year. The disease becomes apparent from age 2 to 7. It first affects muscles in the arms and legs before progressing to the diaphragm, the main muscle that controls breathing, and then the heart.

“By the time they are 12 to 14, they become non-ambulatory and often die by their mid-20s,” Collet said. “These parents are told that not much can be done.”

Unlike many other drugs that focus on extending the time that the boys can walk, Carmeseal-MD works to delay damage to the diaphragm and heart muscles.

“This is the only drug that has the potential to treat both cardiac and respiratory dysfunction, the two leading causes of death,” Collet said.

If the treatment shows promise, Phrixus plans to make it widely available as an unlicensed special in Europe while pursuing FDA approval in the U.S.