The Food and Drug Administration (FDA) has accepted for filing the New Drug Application (NDA) for vamorolone for the treatment of Duchenne muscular dystrophy (DMD).

Vamorolone is a first-in-class dissociative steroidal drug that retains the anti-inflammatory activity of corticosteroids but with a novel mechanism of action. The NDA is supported by data from the randomized, double-blind, placebo- and active-controlled phase 2b VISION-DMD study (ClinicalTrials.gov Identifier: NCT03439670), which evaluated the efficacy and safety of vamorolone in ambulant boys 4 to less than 7 years of age with DMD. Patients (N=121) were randomly assigned to receive vamorolone orally at daily doses of 2mg/kg or 6mg/kg, prednisone 0.75mg/kg/day, or placebo.

Findings showed that treatment with vamorolone 6mg/kg/day met the primary endpoint demonstrating superiority in change of time to stand from supine positioning to standing (TTSTAND) velocity at 24 weeks compared with placebo (treatment difference, 0.06 [95% CI, 0.02-0.10] rises/second from baseline [P =.002]). This corresponded to a clinically relevant improvement in TTSTAND in the vamorolone 6mg/kg/day arm (from 6.0 to 4.6 seconds) and deterioration in the placebo arm (from 5.4 to 5.5 seconds).

Vamorolone was also found to be superior to placebo across multiple secondary endpoints, including TTSTAND velocity for 2mg/kg/day (P =.02), 6-Minute Walk (6MWT) for 6mg/kg/day (P =.003) and 2mg/kg/day (P =.009), and Time to Run/Walk 10 meters (TTRW) for 6mg/kg/day (P =.002).

No statistically significant differences were observed between vamorolone 6mg/kg/day and prednisone across all endpoints. The analysis showed that height percentile declined in patients treated with prednisone but not among those who received vamorolone (P =.02).

The most common adverse events reported with vamorolone were cushingoid features, vomiting and vitamin D deficiency.

A Prescription Drug User Fee Act target date of October 26, 2023 has been set for the application.

References

  1. Santhera and ReveraGen announce FDA acceptance of New Drug Application for vamorolone in Duchenne muscular dystrophy. News release. Santhera Pharmaceuticals and ReveraGen BioPharma, Inc. Accessed January 9, 2023. https://www.globenewswire.com/news-release/2023/01/09/2584775/0/en/Santhera-and-ReveraGen-Announce-FDA-Acceptance-of-New-Drug-Application-for-Vamorolone-in-Duchenne-Muscular-Dystrophy.html.
  2. Santhera and ReveraGen announce positive and statistically highly significant topline results with vamorolone in pivotal VISION-DMD study. News release. Santhera Pharmaceuticals and ReveraGen BioPharma, Inc. June 1, 2021. Accessed January 9, 2023. https://www.reveragen.com/wp-content/uploads/2021-06-01_PR_VamTopline_e_final.pdf.