Vamorolone may prove successful as a novel anti-inflammatory for many indications where pharmacological glucocorticoid steroidal drugs are currently standard of care. The improved safety of vamorolone may prove particularly important in the pediatric populations, where many of the side effects of prednisone can significantly reduce the quality of life of young patients.
The initial clinical development program for vamorolone focuses on Duchenne muscular dystrophy (DMD). DMD is of particular interest as it is the most common single gene disorder, affecting roughly 1:4,000 young boys worldwide. The disease shows a high mutation rate, making it impossible to implement screening programs to effectively identify most families at future risk for DMD (as can be done with Cystic Fibrosis, Tay-Sachs, or other genetic disorders). DMD also is a high unmet need, with no drugs ever having received regulatory approval. Traditional glucocorticoids are considered standard of care for DMD, but the side effect profiles can often make physicians reluctant to prescribe the drug, especially to very young children. Particularly prior to the clinical onset of the disease, the severe side effects are felt to outweigh the benefit in strength and mobility.
If a new chemical entity with reduced side effects proved effective in symptomatic DMD patients (such as vamorolone), the use of the drug could be moved earlier in the disease process, perhaps even at the point of birth. Neonatal screening for DMD is easily accomplished, and over 1 million boys have been screened at birth. However, most neonatal screening programs for DMD are not currently active due to lack of therapies applicable to very young, pre-symptomatic children with DMD.
Use of vamorolone in these earlier stages of disease holds potential to preserve greater muscle function than is seen currently with prednisone or deflazacort, with less of the side effects that have inhibited prescription of traditional glucocorticoids at very young ages. Thus, vamorolone may provide a justification for wide-spread implementation of neonatal screening in all state-mandated panels.
ReveraGen is pursuing parallel regulatory approval in both USA (FDA) and Europe (EMA). In the USA, pre-IND meetings were held with the FDA in October 2013, and the IND was filed December 2014. Phase 1 clinical trials were completed in late 2015 in adult volunteers (SAD and MAD), and have been funded through venture philanthropy contracts by the MDA (USA), Joining Jack (UK), DRF (UK) and Duchenne Children’s Trust (UK). Phase 2a studies in 4-7 yr old steroid-naïve DMD boys (patients that have not taken prednisone or deflazacort) are currently underway. The Phase 2a studies include the option for a 6-month extension study. The DMD clinical program is being developed and run by a collaboration between the CINRG group (www.cinrgresearch.org), and Newcastle University (Kate Bushby and Michela Guglieri). The Phase 2b studies are also expected be in younger 4-7 yr old steroid-naïve boys, with the possibility of accelerated approval.
Vamorolone is being developed as a replacement for existing glucocorticoids, not as an add-on therapy as are all other drugs being developed for DMD. As glucocorticoids are considered standard of care, the regulatory path for replacement of the standard of care can be complex. If vamorolone does show improvements over existing glucocorticoid treatments, then we envision most or all DMD patients to transition to vamorolone, including both very young patients (where glucocorticoids are not standard of care), as well as older patients.