Vamorolone Shows Efficacy With Fewer Side Effects Over 48 Weeks
Treatment with vamorolone continued to show a good safety profile and sustained efficacy across functional assessments after almost one year in boys with Duchenne muscular dystrophy (DMD), according to 48-week results of the Phase 2b VISION-DMD clinical trial.
Data also showed no loss of efficacy in boys who switched from the corticosteroid prednisone to vamolorone. This switch was associated by investigators with a reversal of growth stunting and fewer side effects, including behavioral changes.
“We are delighted about the positive outcome of the pivotal VISION-DMD study as it brings to fruition over a decade of scientific research to design and develop a corticosteroid that has the potential to address very clear unmet medical needs that burden patients and families,” Eric Hoffman, PhD, president and CEO at ReveraGen BioPharma, said in a press release.
ReveraGen is developing vamorolone with Santhera Pharmaceuticals.
Vamorolone is a first-in-class steroid with the anti-inflammatory activity of corticosteroids, the current standard of care in children and adolescents with DMD, but designed to have fewer side effects. It binds to the same receptors as corticosteroids but differs in how it interacts with those receptors, to potentially ease side effects of treatments like prednisone, which can include excessive weight gain, hypertension, behavioral changes, cataracts, and bone fractures.
VISION-DMD (NCT03439670) was a double-blind trial in up to 121 ambulant boys with Duchenne, ages 4 through 6, to test vamorolone against a placebo and prednisone.
Previous results covering its first 24 weeks (six months) showed that treatment with vamorolone led to a significant change in Time to Stand (TTSTAND) velocity, a marker of muscle function that measures the speed at which a patient stands from a lying position. Safety and efficacy findings from this pivotal trial part were deemed sufficient by the U.S. Food and Drug Administration (FDA) to support a request for vamorolone’s approval in treating DMD.
“Now, we are very pleased to announce the completion of the VISION-DMD study, providing longer term data which both confirm earlier findings but importantly also support the potential benefits of vamorolone in overcoming some of the challenges these young children and families face in tolerating long term use of corticosteroids,” said Dario Eklund, CEO of Santhera.
A total of 112 patients completed the full 48 weeks of treatment. Two who had entered the trial’s second part decided to stop treatment, one due to an unspecified adverse event.
The analysis looked at boys initially randomized to placebo or prednisone (0.75 mg/kg daily) who then switched to vamorolone — after a four-week tapering period — at either 2 mg/kg or 6 mg/kg daily for another 24 weeks. It also included patients assigned to vamorolone at either dose for the study’s first 24 weeks, who then continued with the treatment at their assigned dose.
Vamorolone’s safety profile was consistent between week 24 and week 48 among boys who continued on the same dose.
Their body mass index (BMI) — a measure of body fat — was also stable between weeks 24 and 48, and growth velocity was preserved at both doses.
A better safety profile was seen in boys who moved to vamorolone after 24 weeks of treatment with prednisone. Notably, changing to the potential therapy at 6 mg/kg a day led to a 30% reduction in the number of side effects reported and a 60% reduction in side effects typically associated with corticosteroids. Behavioral changes decreased by 60%, a finding of “particular interest,” the companies reported.
Patients in this group given vamorolone at its higher dose also showed a reversal in stunted growth and stabilized BMI, which had increased with prednisone’s use.
Safety and tolerability results were similar for those who switched to vamorolone at its 2 mg/kg daily dose.
Three serious adverse events were reported during the trial, but were considered to be unrelated to vamorolone’s use, the companies reported.
“Short stature, behavioral changes and weight gain are some of the important concerns families a nd patients experience with corticosteroids, often limiting their use or even leading to treatment discontinuation,” said Paula Clemens, MD, a study co-chair at the University of Pittsburgh School of Medicine.
“Based on data from the VISION-DMD study, promising data on restoration of normal growth, fewer side effects impacting behavior and encouraging data on body mass index (BMI) seen with vamorolone, this novel, first-in-class steroid has the potential to emerge as a valuable alternative to the current standard of care for DMD,” Clemens added.
Gains in function from the study’s start reported at week 24 were maintained or improved through week 48 in patients continuously treated with vamorolone at its 6 mg/kg daily dose across all measures: TTSTAND velocity, the North Star Ambulatory Assessment — a 17-item rating scale used to measure functional motor abilities in DMD — and the time to run/walk 10 meters. Results of the 6-minute walk test (6MWT), the distance walked in six minutes, improved at week 48 (48 vs. 37 meters).
Among those continuously treated at its 2 mg/kg daily dose, the higher-dose vamorolone group showed significant superiority in the TTSTAND velocity and 6MWT assessments.
Efficacy gains noted with prednisone in the trial’s first 24 weeks were sustained across all functional tests in patients who switched to vamorolone at high dose.
“These data presented today support our ambition that vamorolone may have the potential to be an alternative to prednisone,” Santhera stated in a letter to the Duchenne community.
“We look forward to commencing the NDA [new drug application] submission with our partner ReveraGen and working with regulators to making vamorolone available as soon as possible,” Eklund added.