DART Therapeutics Inc., an innovative, new-model biotechnology firm focused on developing therapies for duchenne muscular dystrophy (DMD), has started a phase Ib/IIa study of its lead drug candidate, HT-100 (delayed-release halofuginone). The phase Ib study (with a six-month 2a extension) in patients will determine the safety and tolerability of different, increasing doses of HT-100, and explore trends in a range of efficacy endpoints.
HT-100 is an orally available, small molecule drug candidate intended to reduce fibrosis and inflammation and promote healthy muscle fiber regeneration in boys with DMD. The phase Ib/IIa clinical programme will enroll 30 boys and young men with DMD, both ambulatory and non-ambulatory. Participating centers include University of California, Davis Medical Centre, Kennedy Krieger Institute, Johns Hopkins School of Medicine, Maryland, Washington University School of Medicine, St. Louis, Cincinnati Children’s Hospital Medical Centre and Nationwide Children’s Hospital. DART expects to complete the study in mid 2014.
“Treating DMD requires a cocktail of therapies that will change over time,” said Gene Williams, CEO of DART Therapeutics. “We believe HT-100 could be a valuable part of this cocktail even a mini-cocktail on its own because it demonstrates potential to address many different aspects of the disease in parallel, which could make it an exceptionally important therapy for all boys living with DMD.”
DART’s study will include boys aged six through 20, an atypical age range that allows investigators to evaluate HT-100’s safety in a broad population as well as study its effect in different disease stages. Researchers will also evaluate a new endpoint that could make DMD studies faster, more precise, less expensive and inclusive of a larger group of boys. Presently, the six-minute walk (6MW) is the standard endpoint for DMD studies. However, the 6MW has shortcomings including variability and difficulty interpreting the clinical relevance of a given effect size. It also limits study participants to boys who can walk at a certain speed. There are no validated endpoints for very young boys with DMD. The proposed endpoint, electrical impedance myography (EIM), is a simple, non-invasive technique that can measure the health of a muscle and track its changes over time. As a validated endpoint for DMD, EIM would allow researchers to include a wide range of boys in studies and more effectively and rapidly understand how well a treatment is working to halt disease progression.
“Not only do we need several different categories of treatments for DMD—a therapeutic cocktail that might include different components depending on the stage of the disease—we also need new endpoints to improve the quality and speed of our clinical studies,” said Dr Diana Escolar, associate professor of Neurology at Johns Hopkins School of Medicine’s Kennedy Krieger Institute, DART’s chief medical officer and study director. “It is only through this two-pronged approach that we will succeed in our mission to make DMD a chronic, manageable disease instead of a fatal one.”
DMD is the most common of the muscular dystrophies and the most lethal genetic disorder of childhood. It is caused by a genetic mutation that renders boys unable to make functional dystrophin, a protein critical for normal muscle function.