SMT C1100: Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is the most common form of the muscular dystrophies. It is an orphan disease which occurs in about 1 in 3,500 males, with around 30% of DMD cases arising in boys with no familial history of the disease. DMD is caused by the absence of the protein dystrophin.
In DMD the lack of dystrophin protein results in severe and progressive skeletal and heart muscle deterioration resulting death before their mid-twenties. Currently, there is no known cure for the disease.
Summit’s Approach: The Upregulation of Utrophin
SMT C1100 is a small molecule Utrophin upregulator and is the only disease modifying treatment in clinical development that has the potential to benefit all DMD patients. In addition, SMT C1100 is anticipated to be complementary to other therapeutic approaches currently in development. SMT C1100 has been granted orphan drug status in the US and Europe.
Why Utrophin Upregulation?
Utrophin is a naturally occurring protein that is similar to dystrophin and scientists have shown that upregulating (increasing) its production can compensate for the missing dystrophin and help to restore healthy muscle function.
SMT C1100: Disease modifying potential
Results from in vitro and in vivo non-clincial efficacy studies, including one performed in the gold standard mdx mouse model, established the disease modidying potential of SMT C1100:
- Increases utrophin protein in dystrophin deficient muscle cells from DMD patients to levels expected to be of significant therapeutic benefit
- Significantly increases the amount of Utrophin in the gold standard in vivo model (see Figure 1)
- Improves whole muscle function in study that is surrogate to the 6 minute walk test, a primary endpoint in human clinical trials
- Reduces muscle degeneration, fibrosis and chronic inflammation
The results were generated in three independent laboratories including those of world-leading DMD academic Professor Dame Kay Davies FRS (University of Oxford, UK) and published in the leading peer reviewed scientific journal PLoS ONE.
Figure 1: Results from an in vivo study showing the increase in Utrophin protein levels, represented by the white rings, in dystrophin lacking muscles (left) after treatment with SMT C1100 (right)
SMT C1100: Phase I Clinical Trial to Start in Early 2012
In December 2011, Summit entered into a $1.5 million agreement with a group of US based DMD organisations to support a new Phase I clinical study in healthy volunteers. Summit expects to submit a clinical trial application in Q1 2012, with headline results from the study anticipated to be available in Q3 2012. A successful outcome from the Phase I trial could lead to a Phase II study in DMD patients starting in H1 2013. The organisations involved are the Muscular Dystrophy Association, Parent Project Muscular Dystrophy, Charley's Fund, Cure Duchenne, the Foundation to Eradicate Duchenne and the Nash Avery Foundation.
The new clinical trial will evaluate a new formulation of SMT C1100 to see if it can provide consistent levels of the drug in the blood that the non-clinical efficacy studies predicted would be required to confer therapeutic benefit in DMD patients, while also further assessing its safety. The new formulation will be appropriate for use by all DMD patients. A previous Phase I clinical trial of healthy volunteers showed SMT C1100 to be safe and well tolerated in all subjects with no adverse events reported.
If you would like to find out more about our programme please email: dmd@summitplc.com
