Ezutromid Significantly Reduces Muscle Inflammation, Interim Analysis of PhaseOut DMD Trial Shows

Ezutromid Significantly Reduces Muscle Inflammation, Interim Analysis of PhaseOut DMD Trial Shows

A new interim analysis of the PhaseOut DMD clinical trial shows that ezutromid (SMT C1100) significantly decreased muscle inflammation in patients with Duchenne muscular dystrophy (DMD), Summit Therapeutics announced.

Ezutromid is called a utrophin modulator because it is able to trigger utrophin production in people who lack dystrophin, such as DMD patients.

Utrophin is a naturally occurring protein in the muscle, functionally and structurally similar to dystrophin. Previous preclinical-trial studies have shown it can improve muscle performance.

The ongoing Phase 2 study (NCT02858362) is an open-label trial that’s evaluating the efficacy and safety of ezutromid administered over 48 weeks (11 months) in boys with DMD.

Forty DMD patients ages 5-10 and recruited from centers in the U.S. and the U.K. were enrolled in the trial. The boys are treated with a daily dose of 2,500 mg of ezutromid (open-label phase) followed by a 30-day safety follow-up phase.

The primary objective (called the endpoint) is to measure the change in leg muscle parameters by magnetic resonance imaging (MRI) and the levels of ezutromid in the blood at specific times during treatment  at weeks 1, 4, 8, 12, 24, 36 and 48.

Additional (secondary) endpoints include assessing utrophin protein levels and muscle fiber regeneration by analyzing muscle biopsies.

A previous analysis conducted at 24 weeks showed that treatment with ezutromid significantly reduced muscle damage in DMD patients.

Now, researchers showed that the therapy also led to a significant reduction in inflammation, shown by a decrease in the magnetic resonance spectroscopy transverse relaxation time T2 (MRS-T2) at 24 weeks in two leg muscles, the calf muscle (soleus) and the thigh muscle (vastus lateralis).

The median decrease in the calf muscle (38 patients) one of the most reliable leg muscles for monitoring MRS-T2 was -0.861 milliseconds, and in the thigh muscle (37 patients) -0.470 milliseconds, from baseline to 24 weeks.

T2 relaxation time is an advanced technique to detect small structural changes that occur with early degeneration or inflammation. Researchers previously showed that an increase in T2 relaxation time was the result of inflammation.

The reduction in MRS-T2 agrees with the expected activity of ezutromid in stabilizing muscle fiber membranes by increasing utrophin protein expression, leading to reduced muscle damage and inflammation.

All patients enrolled in the study were also undergoing therapy with steroids, previously shown to also lead to MRS-T2 reductions, so the new effects are a result of treatment with ezutromid.

“MRS-T2 is an objective technique used to monitor DMD disease progression as it allows for the precise quantification of changes in muscle breakdown and inflammation. MRS-T2 values typically increase over time in DMD,”  Dr. H. Lee Sweeney, director of the Myology Institute at the University of Florida and co-director of Imaging DMD, said in a press release.

“The decrease in MRS-T2 seen in PhaseOut DMD is encouraging and suggests ezutromid is having a positive effect on muscle health,” Sweeney said. “These data could be an early indication that these patients are experiencing a decrease in disease severity and highlight ezutromid’s potential as a disease modifying treatment. I look forward to seeing further findings from PhaseOut DMD.”

David Roblin, MD, chief medical officer and president of research and development at Summit, said the 24-week analysis shows “encouraging signs of ezutromid activity in PhaseOut DMD. These MRS-T2 findings show a positive impact on downstream muscle health.

“This, combined with the evidence that ezutromid can modulate production of utrophin protein and significantly reduce muscle damage, is further evidence of the potential of ezutromid as a disease modifying approach for the treatment of all genetic forms of DMD,” he added.


  1. Manoj says:

    I read all of your dmd related news. Just would like to inform you that my son 4 year old has DMD and exon 46 to 51 are deleted, report says.

    Could you please tell me that ezutromid is available in India, if yes, what will be cost?

    This medicine can save life of. my child.

    Looking forward to your suggestions please.

    Manoj Sharma

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