Santhera, ReveraGen Advancing Plans for Vamorolone Application
The companies announced Tuesday they had completed a pre-NDA meeting with the U.S. Food and Drug Administration (FDA). In the meeting, the FDA indicated that results from the recently finished pivotal portion of the VISION-DMD clinical trial provide sufficient safety and efficacy data to support an NDA.
“We are very pleased with the positive outcome of this first pre-NDA meeting and look forward to initiating our NDA submission,” Eric Hoffman, PhD, president and CEO of ReveraGen, said in a press release.
The FDA also said it would be acceptable for the companies to do a rolling application for vamorolone — meaning they could submit parts of the NDA as they are ready, rather than waiting until every part of the application is completed to submit all together, as is standard. The companies are planning to start their rolling application early next year.
“The feedback from the FDA on our submission plans is encouraging and an important confirmatory step of the progress we have made in advancing vamorolone as a foundational treatment option in DMD. We now look forward to working with the FDA and other regulatory authorities to bring vamorolone to market as soon as possible,” said Dario Eklund, Santhera’s CEO.
Vamorolone is a first-in-class steroid medication that binds to the same receptors as corticosteroids, which is a type of anti-inflammatory medication used as standard care for DMD. Because of the specific ways in which vamorolone interacts with corticosteroid receptors, the experimental medication is expected to have similar anti-inflammatory potency as corticosteroids, but with fewer side effects.
Although outside the official scope of the pre-NDA meeting, the FDA noted that — since corticosteroids are used in many conditions other than DMD — vamorolone may have potential uses for other indications.
ReveraGen sponsored a Phase 2b clinical trial called VISION-DMD (NCT03439670), which enrolled 121 boys with DMD ages 4–6. Participants were assigned randomly to receive a placebo, a standard corticosteroid called prednisone, or vamorolone at doses of 2 or 6 mg/kg per day. The experimental therapy was given a flavored liquid.
The study’s main goal was to determine the effect of treatment on Time to Stand (TTSTAND), a measure of muscle function that assesses how long it takes someone to go from lying down to standing up.
Top-line results showed that, after 24 weeks of treatment, participants on the higher dose experienced a significant improvement in TTSTAND, from 6.0 to 4.6 seconds on average. Participants on the lower dose of vamorolone also showed an improvement. By contrast, participants on placebo had a slight decrease in TTSTAND over the study, from 5.4 to 5.5 seconds.
Treatment with vamorolone also significantly improved other measures of physical function, namely the six-minute walk test and the time to run/walk 10 meters (32 feet).
The medication generally was well-tolerated in VISION-DMD. The most common side effects associated with treatment were vomiting, vitamin D deficiency, and cushingoid features (physical changes such as abnormal abdominal fat that are linked to high levels of cortisol, a stress hormone with activity similar to corticosteroids).
In addition to data from VISION-DMD, recent data from from another Phase 2 trial called VBP15–003 (NCT02760277), and its extension study VBP15-LTE (NCT03038399), indicated that with 2.5 years of follow-up, treatment with vamorolone delayed the decline in motor function, and was generally well-tolerated.