Eric Hoffman
Center for Genetic Medicine Research, Children’s National Medical Center and Department of Integrative Systems Biology, George Washington University, Washington, DC 20010, USA
Drug development is a lengthy and time consuming process, where it has been suggested that it typically costs $500 million and takes 15 years to bring a drug to market. The high costs become problematic with orphan drugs, where there may be very few patients to prescribe the new drug and distribute costs. Also, there are increasing opportunities for highly targeted drugs, but often in ever more stratified patient populations, so the proportion of orphan drugs is expected to increase dramatically. Methods to decrease the costs and time associated with orphan drug development include early de-risking (reducing late stage expensive failures), and accelerated approval (moving larger efficacy trials to the post-marketing space). VBP15 is a first in human drug developed for Duchenne muscular dystrophy (DMD). Intellectual property for the program was transferred from Children’s National Medical Center to ReveraGen Biopharma. Initial seed funding for lead compound selection was accomplished through support of the Department of Defense CDMRP, and early de-risking of the lead (VBP15) was done in partnership with the National Institutes of Health TRND program. Pre-clinical studies and Phase 1 trials were funded by venture philanthropy support of seven DMD foundations through a risk sharing and profit sharing model based on later drug sales. Phase 2a and 2b trials in DMD patients are to run by international academic networks, with the possibility of accelerated approval after a short-term (3-6 month) trial with a measure of strength as the primary outcome measure. VBP15 is a steroidal compound built on a delta 9,11 backbone, where the drug shows a high affinity for the glucocorticoid receptor, but is effective in dissociating anti-inflammatory transrepression subactivities (retention of efficacy), from the transactivation subproperties associated with side effects (growth stunting, adrenal suppression, immune suppression). VBP15 has shown efficacy in pre-clinical models of multiple chronic inflammatory states, including allergic lung disease, arthritis, multiple sclerosis, inflammatory bowel disease, and sickle cell anemia. Thus, VBP15 holds potential for replacing traditional glucocorticoids in multiple indications, including DMD.