#apaperaday: Efficacy and Safety of Vamorolone Over 48 Weeks in Boys With Duchenne Muscular Dystrophy

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Efficacy and Safety of Vamorolone Over 48 Weeks in Boys With Duchenne Muscular Dystrophy

Today’s pick is from Neurology by Dang et al on the 48 week results of the vamorolone study in Duchenne. doi: 10.1212/WNL.0000000000208112

Duchenne patients use glucocorticosteroids to slow down disease progression. However, this does result in side effects. As an alternative vamorolone is a dissociative steroid that has less of the side effects while still having the positive effects.

The pivotal trial to get vamorolone approved involved 121 patients from 4-7 years old who were steroid naïve. Patients received prednisone, steroids or 2 or 6 mg/kg/day vamorolone for 24 weeks. The results of this part have been reported already:

vamorolone treatment at 6 mg/kg/day had similar efficacy as prednisone. After 24 weeks placebo and prednisone treated patients were split over the 2 and 6 mg/kg/day vamorolone groups, while those on vamorolone stayed on this dose for another 24 weeks.

114 patients were still enrolled when the second stage started and 112 completed it until 48 weeks. The 2 who withdrew were from the 6 mg/kg/day vamorolone group and withdrew due to acute hepatitis or without a reason. Authors first remind us of the 24 week results:

The 2 and 6 mg/kg/day vamorolone treatment resulted in improved time to stand, 6 minute walk test and 10 meter run compared to placebo and equal to prednisone. 6 mg/kg/day also improved north star ambulatory assessment and 4 stair climb studies

After 48 weeks the patients in the 6 mg/kg/day vamorolone group maintained the improvement, while for the 2 mg/kg/group were maintained or declined slightly. For most functional outcomes the 6 mg/kg/day group did better than the 2 mg/kg/day group.

The patients who switched to vamorolone from placebo improved in functional outcomes after the switch for both doses but the 6 mg/kg/day group improved more. Those switching from prednisone maintained function for both doses but the 2 mg/kg/day group showed more variability.

Adverse events were seen, most were not related to vamorolone. Cushingoid features were reported for 14% & 32% of patients in 2 and 6 mg/kg/day vamorolone groups (this is treatment related). No specific side effects were seen for patients switching from prednisone to vamorolone.

Compared to the prednisone group, vamorolone patients had less GI problems and less Cushingoid features. Growth trajectories were normal and bone turnover markers were as well for the vamorolone treated patients, unlike the prednisone groups (stunted growth and bone turnover)

Adrenal suppression was seen for both vamorolone and prednisone groups. This means the PJ Nicholoff protocol has to be implemented also for patients on vamorolone as patients will not produce cortisol in stress situations (e.g. fracture).

Authors discuss that some data had to be assessed remotely because of the pandemic. Furthermore, they caution that many comparisons were made and no multiple testing correction was applied. Still I think the data shows that 6 mg/kg/day vamorolone performs well

What we do not know yet is whether it will continue to perform as well as prednisone with less side effects after longer treatment. As vamorolone is now approved in USA, Europe and UK, the long term treatment data will now be collected.