A phase 1b trial of a drug designed to increase utrophin protein levels in Duchenne MD-affected muscles, appears safe and may have muscle-protective effects
Update (July 7, 2014): Summit PLC, developer of experimental DMD drug SMT C1100, presented additional encouraging findings regarding this drug's apparent effects on DMD-affected muscles at the 13th International Congress on Neuromuscular Disease held in Nice, France, July 5-10, 2014. In a July 7, 2014, press release and at the conference, Summit announced that levels of three key enzymes that leak from damaged muscle cells into the bloodstream were reduced when boys with DMD were treated with oral SMT C1100 for 10 days. The three key enzymes are creatine kinase (CK), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). "These data are consistent with the proposed mechanism of action of the utrophin modulator SMT C1100," the press release said. The proposed mechanism of action of this drug is protection of potentially "leaky" muscle fibers by increasing production and distribution of the utrophin protein. A poster summarizing the conference presentation is located at 13th ICNMD Clinical Presentation.
Preliminary results of a phase 1b trial of the experimental drug SMT C1100 in 12 boys with Duchenne muscular dystrophy (DMD) show the oral compound was safe and well-tolerated at all doses tested but that blood levels of the drug varied among trial participants. The company says the variability in blood levels of the drug may be related to dietary intake in the participants or to other factors related to DMD.
In addition and encouragingly, most of the study participants showed a reduction in blood levels of the enzyme creatine kinase (CK), which leaks out of damaged muscle fibers and is considered an indication of ongoing muscle damage.
Summit PLC, an Oxford, United Kingdom, biotechnology company that has received significant funding from MDA to support the development of SMT C1100, announced these results in a May 21, 2014, press release.
The company says it expects to revise future clinical trials plans to determine the optimal way, either through dietary means or drug formulation changes, to address the blood level variability. Summit plans to start the next clinical trial of SMT C1100 in the fourth quarter of 2014.
Utrophin may help compensate for loss of dystrophin
SMT C1100, in development at Summit with MDA support, is designed to maintain levels of a protein known as utrophin in muscle fibers. This protein is normally made during early muscle development and regeneration but nearly disappears and is replaced by dystrophin as muscle fibers mature.
MDA-supported studies conducted in dystrophin-deficient mice have previously shown that raising utrophin protein levels may help compensate for a lack of dystrophin, which is missing in patients with DMD and diminished in patients with the related disorder Becker muscular dystrophy (BMD). (SMT C1100 may also have benefit in BMD patients, but tests in BMD have not been conducted to date.)
About the phase 1b trial
Trial participants were between 5 and 11 years old, and all received SMT C1100 in this open-label study, conducted in the United Kingdom. (There was no placebo group.)
The 12 participants were divided into three dosage groups, with each group receiving a higher daily dosage than the previous group. Participants received SMT C1100 for 10 days.
Unexpected impact on muscle health markers
"This first-ever trial of a utrophin modulator in DMD patients demonstrated the excellent safety profile of SMT C1100 with the study successfully achieving its primary endpoint," said Glyn Edwards, CEO of Summit. "In addition, the positive impact on the enzyme markers of muscle health was both unexpected and exciting, with these data potentially representing SMT C1100's first signs of activity in DMD patients."
He continued, "Our goal with utrophin modulation is to treat all patients with DMD. Armed with a greater understanding of the importance of diet and other disease-related factors, our future clinical trial plans will be modified and will increase the potential likelihood of achieving this goal."
For more information
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