Vamorolone Demonstrates Continued Safety, Efficacy in DMD Delayed-Start Analysis

Utkarsh Dang, PhD, MSc

Results from part 2 of the phase 2b VISION-DMD study (NCT03439670) showed that steroid-naïve boys with Duchenne muscular dystrophy (DMD) who switched to vamorolone (Santhera & ReveraGen) after 24 weeks of placebo treatment demonstrated improved outcomes on several different timed function test velocities.¹

Led by Utkarsh Dang, PhD, MSc, assistant professor, Carlton University Health Sciences, the data confirmed a disease-modifying effect with vamorolone, which was previously observed in the original 24-week analysis. Vamorolone, an investigational first-in-class dissociative steroid, aims to retain the anti-inflammatory activity of corticosteroids while decreasing the deleterious adverse events (AEs).

Presented at the 2022 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, March 13-16, in Nashville, Tennessee, the open-label study included 121 boys with DMD randomized to placebo for 24 weeks (Period 1) who crossed-over to 2 vamorolone groups (2.0 or 6.0 mg/kg/day) for another 24-week treatment period, otherwise known as Period 2. Change was modeled at weeks 12, 24, 40, and 48 using mixed models for repeated measures for early-starters (vamorolone 2.0 mg/kg/day: n = 30; vamorolone 6.0 mg/kg/day: n = 28) and delayed-starters (placebo-to-vamorolone 2.0 mg/kg/day: n = 14; placebo-to-vamorolone 6.0 my/kg/day: n = 14).

After 24 weeks of treatment with vamorolone, delayed starters demonstrated improvement on multiple efficacy outcomes including Time to Stand Test (TTSTANDV)(week 48 vs week 24, P <.05). Between the two groups, early-starters on vamorolone 6.0 mg/kg/day had increased outcome means relative to the delayed-starters for all 5 outcomes at all time points except for 10 Meter Walk Test.

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At the end of the 48-week period, only the mean for Time to Climb Test was statistically significant between early- and delayed-starters (P <.05). Although the data were not provided, investigators noted that other comparisons (vamorolone 2.0 mg/kg/day throughout vs placebo-to-vamorolone 2.0 mg/kg/day or pooled dose groups) yielded similar findings for the most part.

In the original analysis published in June 2021, both the low- and high-dose groups showed strong efficacy in the study’s primary and secondary end points. The primary end point, superiority in change of TTSTAND velocity, was represented by a difference of 0.06 (95% CI, 0.02-0.10) rises per second from baseline in the treated group (P = .002). These patients had clinically relevant improvements in TTSTAND from 6.0 to 4.6 seconds whereas those in the placebo group had deteriorations from 5.4 to 5.5 seconds.²

Vamorolone showed a favorable safety and tolerability profile over prednisone, the comparator drug in VISION-DMD. The 24-week study was completed by 114 of 121 patients (94%). Both the high- and low-dosages showed favorable safety and tolerability profiles. No patients treated with vamorolone discontinued the study due to treatment-emergent AEs (TEAEs). The vamorolone-treated group had 96 TEAEs in the low-dose group and 91 TEAEs in the high-dose group compared with 120 TEAEs in the prednisone-treated group. High-dose vamorolone was found to be significantly superior to prednisone (P = .02) in a prespecified analysis of clinically relevant AEs.

In November 2021, Santhera and ReveraGen announced the successful completion of a first pre-new drug application meeting with the FDA for vamorolone for the treatment of DMD. In its conclusions from the meeting, the FDA agreed that the efficacy shown in VISION-DMD supports an NDA application and that the results from VISION-DMD and the open-label studies provide sufficient safety data to support an NDA filing. Based on this feedback, the companies stated that they would initiate the rolling NDA submission in Q1 of 2022 but have yet to do formally submit at this point.³

For more coverage of MDA 2022, click here.

REFERENCE
1. Dang U, Guglieri M, Clemens PR, et al. Delayed start analysis of efficacy outcomes in placebo to vamorolone crossover participants in VBP15-004. Presented at MDA Clinical and Scientific Conference; March 13-16. Poster 89.

2. Santhera and ReveraGen announce positive and statistically highly significant topline results with vamorolone in pivotal VISION-DMD study. News release. Santhera. June 1, 2021. https://www.globenewswire.com/news-release/2021/06/01/2239124/0/en/Santhera-and-ReveraGen-Announce-Positive-and-Statistically-Highly-Significant-Topline-Results-with-Vamorolone-in-Pivotal-VISION-DMD-Study.html

3. Santhera and ReveraGen announce successful pre-NDA meeting for vamorolone in Duchenne muscular dystrophy. News release. Santhera. November 17, 2021. https://www.globenewswire.com/news-release/2021/11/17/2335970/0/en/Santhera-and-ReveraGen-Announce-Successful-FDA-Pre-NDA-Meeting-for-Vamorolone-in-Duchenne-Muscular-Dystrophy.html