Vamorolone Shows Efficacy in Duchenne Muscular Dystrophy, Safety Advantages Over Prednisone


Compared with placebo, vamorolone-treated patients showed significantly better outcomes on several secondary and exploratory end points, such as the NorthStar Ambulatory Assessment and time to climb 4 stairs.

Eric Hoffman, PhD, professor of pharmaceutical sciences, Binghamton University

Eric Hoffman, PhD

New 24-week primary efficacy and safety analyses from the phase 2 VISION-DMD trial (NCT03439670) of vamorolone (Santhera, ReveraGen), an investigational first-in-class dissociative steroid for Duchenne muscular dystrophy (DMD), were published in JAMA Neurology.1

These expand on the previously announced findings presented at the 2022 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, March 13-16, in Nashville, Tennessee. All told, the study medication met its primary end point of statistically significant and clinically relevant improvement in Time to Stand Test (TTSTAND) compared with placebo, as well as showed several differences in safety outcomes against competing therapy prednisone, including no negative impact on biomarkers of bone health and no loss of linear growth. From baseline to week 24, patients treated with vamorolone 6 mg/kg per day demonstrated least squares mean (LSM) velocity of 0.05 m/s (SE, 0.01) on TTSTAND compared with –0.01 m/s (SE, 0.01) for those on placebo.

"Data from the VISION-DMD study continues to validate our ambition of developing a steroidal like treatment where we can retain the efficacy of traditional corticosteroids and reduce some of the toxicities that all too often lead to the premature discontinuation of treatment in children with DMD," Eric Hoffman, PhD, professor of pharmaceutical sciences, Binghamton University, and chief executive officer, ReveraGen, said in a statement.2

The study featured 133 males with genetically confirmed DMD with a mean age of 5.4 years, 121 of whom were randomly assigned to either placebo (n = 30), prednisone (n = 31), or low-dose vamorolone (2 mg/kg per day; n = 30) and high-dose vamorolone (6 mg/kg per day; n = 30). Results showed that those on placebo showed a stable course with a slight decline in TTSTAND relative to baseline, whereas the vamorolone 6 mg/kg per day group vs placebo showed improvement by 6 weeks of treatment (LSM velocity, 0.03 m/s [SE, 0.01] vs 0 m/s [SE, 0.01]; P = .02), continued improvement to 12 weeks (LSM velocity, 0.04 m/s [SE, 0.01] vs –0.01 m/s [SE, 0.01]; P = .001) and maintained to 24 weeks of treatment.

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The first-rank secondary end point of change in TTSTAND velocity for the low-dose group vamorolone group vs placebo was met with significance (LSM velocity, 0.03 m/s [SE, 0.01] vs –0.01 m/s [SE, 0.01] ; P = .02). Change from baseline to week 24 for 6-Meter Walk Test (6MWT) for the high-dose group vs placebo (LSM distance, 28.3 m [SE, 9.6] vs –13.3 m [SE, 10.0]; P = .003) and low-dose vs placebo (LSM distance, 23.9 m [SE, 9.7] vs –13.3 m [SE, 10.0]; P = .009), the subsequent secondary end points, was also met.

Exploratory end points, such as NorthStar Ambulatory Assessment (NSAA) total score and time to climb 4 stairs (TTCLIMB) velocity, both showed improvement that favored both the high- and low-dose vamorolone groups compared with placebo. Between the 2 groups, patient reported outcomes such as Pediatric Outcomes Data Collection Instrument (PODCI) and Treatment Satisfaction Questionnaire (TSQM), as well as measures of muscle strength, were not statistically significantly different. Notably, in a prespecified analysis of Psychosocial adjustment and Role Skills Scale III (PARS III) limited to 4 of 5 subscales, findings suggested that treatment with low dose vamorolone showed better adjustment for anxiety and depression compared with prednisone. This finding however was not adjusted after multiple testing.

While the number of patients reporting at least 1 treatment-emergent adverse event (TEAE) was similar between groups, the total count of TEAEs was lowest in the placebo group (n = 77), highest in the prednisone group (n = 121), and intermediate in the 2 vamorolone groups (low dose: n = 97; high dose: n = 91). The only withdrawal from the study was from 1 patient in the prednisone group, owing to an AE of personality change that was viewed by the investigator as possibly related to the drug and abated after cessation of the drug.

Among the notable safety findings, investigators observed a heigh percentile decline in prednisone-treated (–1.88 percentile [SD, 8.81]), but not vamorolone-treated patients (high dose: +3.86 percentile [SD, 6.16]; P = .02). Additionally, there was linear growth delay in the prednisone group but not in the vamorolone groups, consistent with previously reported 2.5-year open-label data. Additionally, both groups showed similar overall gain in body mass index, with increases ranging 0.4 to 0.5 in index z score over the 24-week treatment period.3 For dual-energy X-ray absorptiometry, only total body lean mass index for the prednisone group (n = 24) vs the vamorolone, 2 mg/kg per day, group (n = 18) of 18 comparisons showed significance that survived post hoc adjustment for multiple testing (LSM, vamorolone: 2.61 [SE, 1.42]; LSM, prednisone: 9.62 [SE, 1.29]; unadjusted P < .001; Bonferroni-Holm adjusted P = .007) in favor of prednisone.

On biomarker safety end points, patients on prednisone had marked reductions in serum biomarkers of bone formulation such as osteocalcin and procollagen 1 intact N-terminal propeptide (P1NP) whereas this was not the case for vamorolone (mean osteocalcin: prednisone vs high dose vamorolone, –15.5 ng/mL [SE, 15.8] vs –0.17 ng/mL [SE, 17.7]; mean P1NP: prednisone vs high dose vamorolone, –143.7 ng/mL [SE, 124.6] vs –7.9 ng/mL [SE, 122.1]). Similar results were seen on type 1 collagen cross-linked C-telopeptide (CTX1), a marker of bone turnover (mean CTX1: prednisone vs high dose vamorolone; –320 pg/mL [SD, 174] vs 110 pg/mL [267]; P <.001).

1. Guglieri M, Clemens PR, Perlman SJ, et al. Efficacy and safety of vamorolone vs placebo and prednisone among boys with Duchenne muscular dystrophy: a randomized clinical trial. JAMA Neurol. Published online August 29, 2022. doi:10.1001/jamaneurol.2022.2480
2. JAMA Neurology publishes positive clinical trial with vamorolone in Duchenne muscular dystrophy. Santhera. News release. September 1, 2022. Accessed September 1, 2022.
3. Smith EC, Conklin LS, Hoffman EP, et al. Efficacy and safety of vamorolone in Duchenne muscular dystrophy: an 18-month interim analysis of a non-randomized open-label extension study. PLoS Med. 2020;17(9):e1003222. doi:10.1371/journal.pmed.1003222
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