Lessons learned from developing an oligonucleotide drug for a rare disease

Eteplirsen is a medicine developed for the treatment of Duchenne muscular dystrophy, a neuromuscular disorder that affects 1 in 5000 newborn boys. It was only the fourth drug of its kind ever approved (a splice switching antisense oligonucleotide) and the first with a morpholino chemistry. Its developmental path was constrained by these factors and, although some of the hurdles that had to be navigated at the time have since improved, many persist, particularly in the field of rare diseases. This manuscript presents an account of many of such hurdles, how they influenced eteplirsen’s development and how some of them may be avoided.