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Efficacy and Safety of Vamorolone in Duchenne Muscular Dystrophy: A 30-Month Nonrandomized Controlled Open-Label Extension Trial.

#apaperaday: Efficacy and Safety of Vamorolone in Duchenne Muscular Dystrophy

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Efficacy and Safety of Vamorolone in Duchenne Muscular Dystrophy: A 30-Month Nonrandomized Controlled Open-Label Extension Trial.

Today from the office again with a paper from JAMA Network Open by Mah et al on 30 months open extension data with vamorolone in Duchenne patients. Doi 10.1001/jamanetworkopen.2021.44178.

Duchenne patients are treated with glucocorticosteroids (GC). This slows down disease progression but also causes many side effects, including weight gain, Cushing syndrome, short stature, behavior changes, lower bone density, cataracts

Vamorolone is a steroidal anti-inflammatory compound that lacks an 11 beta-hydroxy-carbonyl group thus having a contact site less for the GC receptor. Furthermore, vamorolone is also a potent agonist of mineralcorticoid receptors.

The hope is that vamorolone would have the same beneficial effects as GC, but would induce less side effects. A dose finding study was done in 2017 for 6 months, followed by an open label extension (OLE) using doses of 2 and 6 mg/kg/day. The paper reports results of 2 years OLE.

Authors analyzed 21 patients for whom 30 months data was available (6 months 2 or 6 mg/kg dose in dose finding and 24 months OLE with 2 or 6 mg/kg). Comparing 30 months results to baseline authors saw no difference in time to stand, 6 minute walk distance (6MWD) and NSAA score.

Authors then compared the patients to a natural history cohort (NH, 75 DMD patients treated with steroids). Here the challenge was that for many patients no 30 month follow up data was available. Authors resorted to a prespecified sensitivity analysis to allow comparison.

This revealed there was no difference between GC and vamorolone treated patients for functional outcome measures (6MWT, NSAA) or the risk of losing a function on the NSAA. The vamorolone treated patients had less height reduction than GC treated patients.

In conclusion the data suggest vamorolone treatment has the same functional effects as GC, but less side effects. However, for now this is based on suboptimal comparison. An almost completed placebo-controlled trial will provide real evidence of (hopefully) safety and efficacy.

Authors indicate the study has limitations, the already mentioned difficulty of limited NH data and the open label nature. Furthermore, authors stress that additional, longer term studies are needed to evaluate if vamorolone can induce adrenal suppression.

I am looking forward to the vamorolone placebo-controlled trial data – really hope this will show safety and efficacy. Furthermore, I think this paper highlights very well the importance of having long term NH data – such as is being collected in the Duchenne Center NL.


Pictures by Annemieke, used with permission.