Ezutromid (SMT C1100) was an investigational therapy developed by Summit Therapeutics for the potential treatment of Duchenne muscular dystrophy (DMD), a genetic disorder characterized by progressive muscle degeneration and weakness.

The development of ezutromid was stopped after a Phase 2 clinical trial failed to reach its objectives.

How ezutromid was thought to work

DMD is caused by a mutation in the gene that encodes for dystrophin, a protein that plays an essential role in maintaining the integrity of muscle cells. Utrophin is a naturally occurring protein with similar function and structure to that of dystrophin. It is produced mainly during the early stages of muscle fiber development, but its production stops when muscle fibers are mature. This is when dystrophin takes over. Utrophin also is produced in the early stages of the repair process after a muscle fiber is damaged.

Ezutromid was a compound that modulated utrophin production, i.e., utrophin levels are maintained in order to substitute for dystrophin in mature muscle fibers. It was thought that utrophin modulation had the potential to slow, or even stop, the progression of DMD regardless of the type of mutation causing the disease.

Ezutromid in clinical trials

After two Phase 1 clinical trials showed that two ezutromid formulations called F3 and F6, were well-tolerated, ezutromid entered a Phase 2 trial (NCT02858362, PhaseOut DMD) to assess its safety and efficacy. 

After a 28-day screening and baseline phase, 40 boys with DMD received either 1,000 mg (F3 formulation) or 2,500 mg (F6 formulation) of ezutromid twice daily for 48 weeks.

The primary endpoint of the study was the change from baseline in magnetic resonance imaging (MRI) parameters related to fat infiltration and inflammation of the leg muscles. Additional endpoints included utrophin protein and muscle fiber regeneration level from muscle biopsies, safety, pharmacokinetic measures (how the compound moves in the body), and exploratory measures assessed by the six-minute walk test (6MWT), North Star Ambulatory Assessment, and patient-reported outcomes.

Interim results from a 24-week analysis suggested that ezutromid could have a clinical benefit. Muscle damage and inflammation were reduced compared to baseline, which was shown by the analysis of muscle biopsies and MRS transverse relaxation time T2T2 relaxation time allows the detection of small structural changes that occur in early muscle degeneration or inflammation. It has been shown that inflammation increases T2 relaxation time.

However, when the results from assessments after 12, 24, 36, and 48 weeks were taken together, it was seen that ezutromid did not provide any significant benefit for the patients. Based on this finding Summit Therapeutics decided to discontinue the development of ezutromid therapy for the treatment of DMD. 

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