Rare Daily Staff

Santhera Pharmaceuticals and ReveraGen BioPharma reported positive topline results from the VISION-DMD study, demonstrating robust efficacy across multiple efficacy endpoints and favorable safety and tolerability of vamorolone in the treatment of patients with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a rare inherited X-chromosome-linked disease, which almost exclusively affects males, and is characterized by inflammation that is present at birth or shortly thereafter. Inflammation leads to fibrosis of muscle and is clinically manifested by progressive muscle degeneration and weakness. Major milestones in the disease are the loss of ambulation, the loss of self-feeding, the start of assisted ventilation, and the development of cardiomyopathy. DMD reduces life expectancy to before the fourth decade due to respiratory and/or cardiac failure.

VISION-DMD is a pivotal phase 2b study designed to demonstrate efficacy and safety of vamorolone compared to placebo and prednisone (active control) in the treatment of DMD. In the first 24-week double-blind period, 121 ambulant boys aged 4 to 7 years with DMD were randomized to receive vamorolone (low dose 2 mg/kg/day or high dose 6 mg/kg/day) or prednisone (0.75 mg/kg/day) or placebo. A second period of 24 weeks, where all participants receive vamorolone treatment on either of the two dose levels, will continue to capture additional longer-term safety and tolerability data.

The study met its primary endpoint of superiority in change of time to stand from supine positioning to standing (TTSTAND) velocity with vamorolone 6 mg/kg/day versus placebo. This corresponds to a clinically relevant improvement in TTSTAND in the vamorolone 6 mg/kg/day group from 6.0 to 4.6 seconds and a corresponding deterioration in the placebo group from 5.4 to 5.5 seconds. The study also met secondary endpoints for Six-Minute Walk (6MWT) and Time to Run/Walk 10 meters (TTRW) tests, which achieved statistical significance versus placebo. Vamorolone showed a favorable safety and tolerability profile over prednisone and did not show stunting of growth as reported with conventional corticosteroids. The study completion rate at 24 weeks was 94 percent (or 114 of 121 participants).

“The treatment effect translates into the potential to delay disease progression by about two years and indicates disease modifying potential of vamorolone,” said Dario Eklund, CEO of Santhera.

Santhera plans to submit a New Drug Application (NDA) in the United States in the first quarter of 2022 and request a priority review based on the Fast Track designation granted by the U.S. Food and Drug Administration.

The VISION-DMD study continues to 48 weeks and will, subject to a positive outcome, deliver data for the submission of a marketing authorization application in Europe in the second quarter of 2022. Upon approval, Santhera intends to commercialize vamorolone for the treatment of DMD through its own organization in the United States and main markets in Europe and is seeking collaborations outside those regions for DMD and for additional indications worldwide. Santhera estimates the peak sales potential for vamorolone in the DMD indication to be more than $500 million in the U.S. and the largest five European countries combined.

Vamorolone is a first-in-class dissociative steroid that retains the anti-inflammatory activity of corticosteroids while decreasing the deleterious side effects. As such, vamorolone could emerge as a promising alternative to existing corticosteroids, the current standard of care in children and adolescent patients with DMD. There is substantial unmet medical need in this patient group as high-dose corticosteroids have significant systemic side effects that diminish patient quality of life.

Vamorolone was discovered by ReveraGen BioPharma and is being developed in collaboration with Santhera, which owns worldwide rights to the drug candidate in all indications through an agreement with ReveraGen and Idorsia signed in September 2020.

The vamorolone development program has received funding from several international non-profit foundations and patient organizations, the U.S. National Institutes of Health, the U.S. Department of Defense, and the European Commission’s Horizon 2020 program. It has been granted Orphan Drug status in the United States and in Europe and has received Fast Track and Rare Pediatric Disease designations by the FDA and Promising Innovative Medicine (PIM) status from the U.K. MHRA.

Photo: Dario Eklund, CEO of Santhera

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