#MDA2021 – Long-term Vamorolone Slowed Disease Progression in DMD Boys

Editor’s note: The Muscular Dystrophy News Today team is providing in-depth coverage of the 2021 MDA Virtual Clinical and Scientific Conference, March 15–18. Go here to read the latest stories from the conference.

Long-term treatment with the experimental steroid therapy vamorolone safely and effectively delays motor function decline in boys with Duchenne muscular dystrophy (DMD), according to final, 2.5-year data from a Phase 2 clinical trial and its extension study.

Notably, these benefits were more pronounced with higher doses of the therapy and in boys treated earlier in life (before age 5). Vamorolone was associated with fewer side effects than those typically seen with standard corticosteroids.

These findings, supporting vamorolone as a potential therapy for DMD, were shared by Utkarsh Dang, PhD, an assistant professor at Binghamton University, in an oral presentation at the 2021 MDA Virtual Clinical and Scientific Conference, held March 15–18.

The presentation was titled “2.5-years of Vamorolone Treatment in Duchenne Muscular Dystrophy: Results of an Open Label Long-Term Extension.”

Conventional corticosteroids used for treating DMD, such as prednisone and Emflaza (deflazacort), “have been shown to delay loss of milestone function by two to three years,” Dang said. 

However, their continued use “comes with a lot of side effects,” which has become a major concern in the care of these patients.

As opposed to standard corticosteroids, vamolorone — a first-in-class steroidal product — has a mechanism of action that “dissociates efficacy from safety,” causing fewer and less-severe side effects without compromising its anti-inflammatory properties.

The therapy, given once a day as an oral, flavored liquid, is being developed by ReveraGen BioPharma and Santhera Pharmaceuticals, which holds the therapy’s worldwide rights in all indications.

The Phase 2 VBP15–003 clinical trial (NCT02760277) evaluated the safety and effectiveness of six months of treatment with one of four doses of vamolorone (0.25, 0.75, 2, or 6 mg/kg per day) in 48 boys, ages 4–7, with DMD.

All 46 boys who completed the trial chose to enter its long-term extension study, called VBP15-LTE (NCT03038399), in which they continued treatment, at a daily dose of 2 or 6 mg/kg — those linked to greater therapeutic benefits in VBP15-003 — for up to two years.

Participants’ motor function was assessed mainly through five outcome measures. These included the speed at which boys were able to stand, climb stairs, and run or walk 10 meters (about 11 yards), as well as the 6-minute walk test, which measures the distance a patient can walk in six minutes, and the North Star Ambulatory Assessment (a standard measure of DMD severity).

Previous 18-month data from a combination of VBP15–003 and VBP15–LTE studies showed that vamolorone led to clinically meaningful improvements in all motor outcomes analyzed, and caused fewer side effects than those reported for standard corticosteroids.

Findings at the end of the long-term extension study, totaling 2.5 years of vamolorone treatment, now were presented at the meeting.

Half of the 46 patients entering VBP15–LTE and initially assigned 2 or 6 mg/kg of vamolorone continued treatment at these high doses, while the other half was dose-escalated to the high doses.

Five (10.9%) patients discontinued the long-term study: three due to participation in other trials; one due to study burden; and another due to loss of muscle strength.

Results showed that vamolorone led to motor function improvements among boys younger than 5, and to disease stability in the 5-and-older group.

In addition, earlier initiation of high-dose vamorolone delayed motor function decline, compared with dose-escalation six months later. These dose-related group differences were detected from the first six months of treatment.

Notably, after switching to high-dose vamorolone, boys originally on low doses started “to do better and followed the overall trajectory” of those always on high dose, but “they didn’t catch up,” Dang said.

The findings supported a disease-modifying effect for vamorolone and highlighted the importance of early and high-dose treatment.

Long-term vamorolone treatment was generally safe and well-tolerated, with the most common adverse events (side effects) including common cold (37%), cough (34.8%), fever (34.8%), and vomiting (30.4%).

Rates of most common and treatment-related adverse events appeared to show a dose-response, being more frequent with the highest dose (6 mg/kg). There were two serious adverse events, but these were deemed unrelated to vamorolone. No patient died during the study.

“Adverse events typically associated with corticosteroids were consistent with previous 18-month published report and remain less than published reports of corticosteroid clinical trials,” Dang said.

Specifically, there were few reports of Cushingoid syndrome, fewer events of weight gain, and no reports of excessive hair grow or behavioral changes. The investigational therapy also was not associated with other common side effects of traditional corticosteroids, such as stunted growth, reductions in bone-related molecules, and insulin resistance.

“These data provide evidence of the safety and clinical benefits of vamorolone in the long-term treatment of DMD,” Dang added.

Vamorolone also is being tested against a placebo or prednisone in 121 Duchenne boys, ages 4 to 6, and able to walk, in VISION-DMD, a 48-week Phase 2b trial (NCT03439670).

Should top-line results from this trial be positive, they are expected to support an application to the U.S. Food and Drug Administration requesting the approval of vamorolone for DMD in early 2022.