Using PBPK for Label Recommendations in Rare Disease: Deflazacort for Duchenne Muscular Dystrophy
Deflazacort (Emflaza®) was fast-tracked, given orphan status, and approved by the US FDA in February 2017 for patients 5 years and older with Duchenne Muscular Dystrophy (DMD). Emflaza is a corticosteroid that works by decreasing inflammation and reducing the activity of the immune system. It is also a pro-drug, which undergoes conversion in the plasma by esterases, taken to the liver and metabolized by CYP3A4 enzymes. Not only did this raise a concern about the drug’s drug-drug interaction (DDI) liability, but DMD patients typically take multiple other medicines to support the heart, breathing muscles, bone health, gastrointestinal symptoms, hormone levels, common antibiotics, and to manage pain.