Vamorolone Safely Improves Muscle Function in DMD Boys, Trial Finds

Top-line data from the VISION-DMD Phase 2b clinical trial evaluating vamorolone in boys with Duchenne muscular dystrophy (DMD), showed efficacy across primary and secondary study goals. The investigational therapy was also well-tolerated with a favorable safety profile.

Santhera Pharmaceuticals, which is developing the treatment in partnership with ReveraGen BioPharma, plans to apply to the U.S. Food and Drug Administration (FDA) early in 2022, requesting a priority review of vamorolone to treat DMD. 

“We are thrilled about the positive results of the VISION-DMD study as it represents a culmination over a decade of scientific research,” Eric Hoffman, PhD, president and CEO at ReveraGen, said in a press release. “We are grateful to have been able to gather such important data and would like to thank all VISION-DMD participants, their families, and caregivers, as well as investigators and study personnel, for their commitment to this ongoing program.”

Vamorolone is a first-in-class steroid that retains corticosteroid anti-inflammatory activity, the current standard of care in children and adolescents with DMD, but with fewer side effects.

VISION-DMD, a 48-week (almost one year) study (NCT03439670), is testing the safety and efficacy of vamorolone at 2 and 6 mg/kg, given daily as an oral, flavored liquid, against the corticosteroid prednisone (0.75 mg/kg/day) and a placebo in 121 boys, ages 4 through 6, with DMD and able to walk. 

Top-line results covered data from the first 24 weeks (six months), and met the study’s primary goal of a significant change in the Time to Stand (TTSTAND) velocity — a recognized marker of muscle function, which measures the speed at which a participant stands from a lying position. 

In those given 6 mg/kg of vamorolone each day, TTSTAND velocity showed a treatment difference of 0.06 rises per second over placebo, which corresponded to a clinically meaningful improvement to 4.6 seconds, from 6.0 seconds before treatment (a baseline measure). In contrast, patients assigned to placebo showed a corresponding deterioration from 5.4 to 5.5 seconds.

The study also showed vamorolone significantly increased TTSTAND velocity for those who received 2 mg/kg daily over placebo, as well as the 6-minute walk test at both doses, which measures the distance walked in six minutes, and the Time to run/walk 10 meters (TTRW) test at 6 mg/kg daily. 

No statistically significant differences were seen between vamorolone at 6 mg/kg each day and prednisone across all efficacy outcomes.

Regarding safety, 114 of the 121 (94%) boys enrolled completed 24 weeks of treatment. Vamorolone at both doses showed a favorable safety and tolerability profile, with no severe or worse treatment-emergent adverse events (TEAEs) or adverse events that led to study discontinuation.

A total of 96 TEAEs were reported at 2 mg/kg each day, 91 at 6 mg/kg daily, while 120 were reported in those given prednisone. In a pre-planned subgroup analysis, vamorolone at 6 mg/kg each day was significantly superior to prednisone. 

Standard corticosteroids have been shown to stunt growth with continued use. However, in open-label studies over 2.5 years, vamorolone was reported to not stunt growth and to have fewer side effects than those typical of corticosteroid use. At 24 weeks of VISION-DMD, vamorolone at 6 mg/kg/day versus prednisone showed a significant difference in growth velocity. 

“Stunting of growth is a major concern of families and patients treated with corticosteroids, and we are delighted to see this superiority of vamorolone proven in this double-blind study,” said Paula Clemens, MD, study co-chair at the University of Pittsburgh School of Medicine.

VISION-DMD will continue for another 24 weeks, with all participants receiving vamorolone at a 2 or 6 mg/kg daily dose and assessed for the treatment’s tolerability and efficacy. Final data is expected later this year, the companies said. 

“The strength of evidence for both efficacy and safety of vamorolone over such a wide dose range … allows clinicians to individually tailor treatment of Duchenne patients by starting at the higher 6 mg/kg/day dose of vamorolone with equivalent efficacy to daily prednisone and titrate [lower] the dose according to how well the treatment is tolerated whilst maintaining optimal efficacy,” said Craig McDonald, MD, a professor at the University of California, Davis.

“I am enthusiastic that this approach may allow patients to avoid side effects that currently lead to discontinuing steroid treatment, meaning they are able stay on for longer,” McDonald added.

Based on the entire 48-week study data, the company also plans to apply for vamorolone’s approval in Europe toward mid-2022. If approved, Santhera intends to market the treatment in the U.S. and Europe, and to seek collaborations worldwide. 

“Today’s news is a tremendous milestone for patients and Santhera as we further advance vamorolone as a foundational treatment option in DMD,” said Dario Eklund, CEO of Santhera. “The treatment effect translates into the potential to delay disease progression by about two years and indicates disease-modifying potential of vamorolone.” 

“We now look forward to working with regulatory authorities to bring vamorolone to DMD patients, first in the U.S. and subsequently in Europe,” he added.