Vamorolone, a dissociative synthetic steroid, co-developed by ReveraGen and Santhera, has been evaluated for its anti-inflammatory effects in Duchenne muscular dystrophy (DMD) in two trials. The first trial evaluated two oral doses of vamorolone (2 and 6 mg/kg/day) for 30 months in 46 DMD boys aged 4 to 7 years after a dose escalation phase and in comparison with an external cohort of patients (natural history of CINRG) treated in real life with corticosteroids.
The second study evaluated the same doses of vamorolone in 121 boys aged 4 to 7 years (divided into 4 groups) for 6 months compared to oral prednisone 0.75 mg/kg/day and placebo.
The results show that :
- Vamorolone is well tolerated in the medium and long term, based on blood constants, liver and urine markers obtained. In the second trial, the same number of (resolved) adverse events were observed in all treatment groups.
- Weight gain was similar with vamorolone and corticosteroids, particularly prednisone, as observed in the second trial. The 6 mg/kg/day dose of vamorolone appeared to cause greater weight gain: 10 participants in the first trial had to switch to the 2 mg/kg/day dose to stabilise this weight gain.
- Vamorolone did not interfere with growth, which was normal in participants in the first trial compared to the CINRG cohort on steroids, and in the second trial compared to prednisone.
- Blood osteocalcin levels and other markers of bone mineralisation were better maintained on vamorolone than on prednisone, where they decreased.
- Motor function was assessed with the 6-minute walk test, the speed test for walking or running 10 metres, getting up from the floor or climbing 4 steps, and with the use of the NSAA functional scale, showing similar efficacy results over 6 and 30 months between vamorolone and conventional steroids.
Based on these encouraging results, Santhera has filed two marketing authorisation applications for vamorolone in DMD, in Europe and the United States. A response is expected in the second quarter of 2023.
