番茄社区

LOS ANGELES -- The investigative utrophin modulator ezutromid showed promise in treating Duchenne muscular dystrophy, according to an interim analysis of an open-label, phase II clinical trial.

Ezutromid appeared to have significantly deceased inflammation in the calf muscle of Duchenne patients after 24 weeks, reported Anne Heatherington, PhD, of Summit Therapeutics in Oxford, England, and colleagues at the American Academy of Neurology annual meeting.

Ezutromid is a small-molecule, first-in-kind utrophin modulator. Utrophin, a naturally occurring protein physically similar to dystrophin in developing and repairing muscle, may act as functional replacement for dystrophin.

In this study presented in an , 40 boys with Duchenne muscular dystrophy who were ambulant, ages 5 to 10 years, and treated with stable corticosteroids received 2,500 mg or 1,000 mg of ezutromid orally twice a day.

The researchers biopsied the boys' muscles to evaluate degeneration and used magnetic resonance spectroscopy transverse relaxation time T2 (MRS T2) to measure changes in water molecules and assess inflammation. Repeated cycles of muscle damage and repair create inflammation and causes T2 time to increase with disease progression.

At 24 weeks, muscle biopsies showed a statistically significant drop in developmental myosin, signifying less muscle degeneration. Despite this decrease, mean utrophin intensity was maintained. "These two results combined indicate that we have target engagement and reduction in muscle damage," Heatherington said.

MRS results demonstrated a statistically significant reduction in T2 time for the soleus muscle and a small increase in the fat fraction of both the soleus and vastus lateralis muscles. This suggested an early effect of ezutromid on downstream muscle health on background of stable steroids, Heatherington noted.

"When we look at the data collected from the arm muscles of the boys in the biopsy, and we compare that to the T2 data from the leg muscles of the boys, we see a high correlation where most boys who had a decrease in developmental myosin also had a decrease in T2," she said. "These data suggest that ezutromid reduces muscle damage and improves muscle health while continuing to be safe and well tolerated."

"This report provides additional evidence for the safety of ezutromid, and provides support for the presumed biologic mechanism of its effect in patients with dystrophinopathy (Duchenne muscular dystrophy)," observed Lyell Jones, Jr., MD, of the Mayo Clinic in Rochester, Minnesota, who was not involved in the study. "The mechanism of this drug's action is different from the mechanism of other disease modifying agents like corticosteroids or exon-skipping treatments."

"While promising, insights into efficacy will need to await results of a randomized, controlled, blinded clinical trial," he told 番茄社区. "If it demonstrates efficacy in that setting, it would provide yet another tool in the care of patients with this difficult disease."

In 2016, the FDA approved eteplirsen (Exondys 51), the first-ever drug for Duchenne muscular dystrophy. Earlier this month, Pfizer began the first human trial of to treat the disorder.

The full phase II trial analysis at 48 weeks for ezutromid should be completed later this year, and a phase III placebo-controlled trial started in 2019.