Marathon Pharmaceuticals Study May Support Deflazacort Approval For DMD

The glucocorticoid deflazacort might shortly be approved for treatment of Duchenne muscular dystrophy (DMD) in the US. In preparation for the approval process, Marathon Pharmaceuticals have released new data showing that in young rats, the drug causes a slowing of growth but is otherwise safe.

Deflazacort has been used extensively for the treatment of DMD around the world. Despite this, the drug is not approved for this particular use. Marathon Pharmaceuticals have, however, started the process to gain approval from the U.S. Food and Drug Administration for the use of deflazacort for DMD.

Long-term treatment with glucocorticoids is linked to a host of side effects such as growth retardation in children — a treatment consequence mediated through complex effects on other hormonal systems. While deflazacort has been used extensively in children with Duchenne muscular dystrophy, no controlled studies of the drug’s effects on growth in experimental animals have previously been published.

To study the growth processes, researchers exposed rats to the drug for about 70 days, starting when the rats were 21 days old. The animals were then allowed to the point of recovery until they were 133 days old. This development period can be compared to the human age of 2 until early adulthood. In total, the team analyzed data from 180 male and 180 female rats.

Findings revealed that deflazacort reduced weight gain in rats during the treatment period. The decrease was related to the dose, and the largest growth impairment was seen in animals receiving the highest dose. While weight gain was slowed in both males and females, it was more evident in male rats.

The doses used in the study cannot be directly translated to human doses, since rats are more sensitive to the drug than humans. Nevertheless, the animals were exposed to levels about 2-3 times higher compared to what is used in children and adolescents with DMD.

The researchers then measured weight gain during a recovery period of 52 days, during which the treated animals gained more weight than controls.

The team analyzed a large set of other parameters, and found that the drug had effects similar to what can be expected after glucocorticoid treatment, such as a thinning of the outer layer of the bones. These effects were also reversed when treatment was stopped.

Importantly, no effects were observed on sperm motility or density, nor any other changes in the testes of rats. Also, the treatment did not induce any changes in rats’ brains or peripheral nervous systems.