News Summary of paper published: Phase IIa trial in Duchenne muscular dystrophy shows vamorolone is a first-in-class dissociative steroidal anti-inflammatory drug Positive results have been released from the first in-patient clinical study of vamorolone, a trial part funded by Duchenne UK. The drug was shown to have an improved safety profile compared to the commonly prescribed glucocorticoid prednisone. This open-label phase IIa trial of vamorolone enrolled 48 ambulant boys between 4 and 7 years old, who had never taken glucocorticoid steroids. Each patient was given one of 4 different doses of vamorolone for 2 weeks, with a 2-week follow up with no drug. The study was designed to determine the safety vamorolone in patients with DMD. No clinically significant safety concerns were observed- even at the high dose. Vamorolone shown to have improved safety profile compared to prednisone. Vamorolone shown to have anti-inflammatory effects and to stabilise the muscle (myofiber) membrane. Vamorolone shows potential for improvement in bone safety compared to prednisone. Dose dependant decrease in CK observed after just 2 weeks. All study participants completed the 4-week trial and were invited to enrol in a 24-week Phase II extension study. Vamorolone is a drug being developed by ReveraGen Biopharma, which could provide an alternative to the current standard of care for DMD, glucocorticoid steroids. Glucocorticoid steroids, such as prednisone and deflazacort, are known to slow disease progression in DMD through their anti-inflammatory properties. However, they have a vast array of severe side effects including weight gain, stunted growth, increased bone fragility, delayed puberty, metabolic disturbance, adrenal suppression, adverse effects on mood and behaviour and others. The structure of vamorolone is very similar to glucocorticoid steroids, and they work using the same mechanism: by binding to and activating the glucocorticoid receptor. The glucocorticoid receptor regulates genes controlling development, metabolism and immune response. An activated glucocorticoid receptor upregulates the expression of anti-inflammatory proteins. The glucocorticoid/receptor complex couples up to form a dimer (2 compounds attached together). The vamorolone/receptor compound, on the other hand, remains as a single ‘monomer’. It has been shown that receptor/ligand monomers (formed commonly with vamorolone) mediate the anti-inflammatory effects of steroids. But receptor/ligand dimers (formed with glucocorticoids) appear to be responsible for the severe side effects of glucocorticoid drugs. Vamorolone will now enter a phase 2b study, VISION-DMD, to assess the safety and efficacy of vamorolone over a 24-week period. The study, which will enrol a total of 120 boys, will compare two different doses of vamorolone to a standard dose of prednisone and a placebo. To find out more about this trial visit the DMD Hub website. Read the full paper published with details of the IIa trial and results here.