Clinical trial Duchenne muscular dystrophy

Summit, a UK drug company, announced on the 9th December 2013 that a boy with Duchenne muscular dystrophy (DMD) had taken the first dose of SMT C1100 in the phase 1b clinical trial. SMT C1100 is an oral drug designed to increase the amounts of a protein called utrophin in the body. It is thought that utrophin might be able to substitute for the dystrophin that is missing in boys with DMD because the two proteins are very similar. If this drug proves to be effective it may also be applicable to individuals with Becker MD.

Our bodies naturally make small amounts utrophin protein in certain parts of the body and at certain times. Research in mice and dogs lacking dystrophin has shown that increasing the levels of utrophin protein in the muscles can prevent muscle damage and reduce muscular dystrophy symptoms.

Professor Dame Kay Davies’ laboratory at the University of Oxford has been researching utrophin for more than 20 years and in recent years, in collaboration with Summit, they discovered SMT C1100 which was able to increase the amount of utrophin in a mouse model of DMD. SMT C1100 has been tested in a phase 1 trial in healthy volunteers and it was shown that enough of the drug was absorbed into the bloodstream to potentially have a positive effect on the muscles.

The phase 1b trial was conducted at four UK hospitals and involved 12 boys with DMD between the ages of 5 and 11. The trial amied to further test the safety of the drug and determine the dose to be used in a larger phase 2 trial. The 12 boys were divided equally into three groups, each receiving a different daily dose for ten days. Evidence of the effectiveness of SMT C1100 won’t be known until the phase 2 trial has been completed, and it is likely that any positive results will need to be confirmed in an even larger phase 3 trial.

The progression of SMT C1100 into clinical trial has been eagerly awaited because the utrophin approach to treating DMD has the advantage that it could be used to treat all boys with DMD, no matter what their genetic mutation is. Other approaches such as exon skipping need to be tailor made to correct the particular genetic error and each drug only has the potential to treat a subset of patients.

“SMT C1100 is a promising treatment that has the potential to improve the life of all patients with DMD, irrespective of the underlying dystrophin fault,” commented Dr David Roblin, Summit’s Chief Medical Officer. “There is an urgent need to develop effective medicines for DMD patients and this study forms an important step in our clinical plans towards establishing SMT C1100 and utrophin modulation as a viable treatment that could slow or even stop the progression of this devastating condition.”

UPDATE: Preliminary results released May 2014
Preliminary results of the trial were released in May 2014 which showed that SMT C1100 was safe and well-tolerated at all dose levels. Encouragingly, reduced creatine kinase (CK) levels (a marker of damaged muscle fibres) were also noted. However, this will need to be confirmed in future clinical trials because CK levels are known to fluctuate during the course of the disease, there were only a small number of participants in this trial and there was no placebo control.

Levels of the drug in the blood stream were variable between participants. Only two boys had amounts in their blood comparable to the levels achieved in the healthy adults in the phase 1 trial and levels were lower in the other ten. The company speculates that diet or other disease related factors may be the cause. Summit now plans to address this variability in drug uptake either by dietary changes or by modifying the formulation of SMT C1100 before starting further trials later this year.

Further information

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Updated 30 May 2014