Santhera: Study results from Duchenne muscular dystrophy patients

• Results from 112 patients with DMD who completed the study confirm maintenance of efficacy and benefits in safety and tolerability of treatment with vamorolone over 48 weeks
• AGAMREE has shown safety benefits in patients switching from standard of care corticosteroids in terms of recovery of bone health and growth
• More than 200 patients have now been treated with vamorolone for up to 84 months across clinical studies and access programs
• AGAMREE is the only approved medication in the European Union (EU) for treating all patients from age 4 years with DMD [1], and the first DMD treatment approved across the U.S., EU and UK

The publication reports the results of the 48-week treatment with vamorolone in patients with DMD in the VISION-DMD study, supporting the long-term efficacy and safety profile of vamorolone and concluding that vamorolone was generally well tolerated, consistent with the 24-week study findings, as published previously in JAMA Neurology [3].

The Neurology publication states: “Vamorolone is a dissociative corticosteroid that selectively binds to the glucocorticoid receptor and has shown similar efficacy and reduced safety concerns in comparison with prednisone in Duchenne muscular dystrophy (DMD) [3]. This study [VISION-DMD] was conducted to determine the efficacy and safety of vamorolone over 48 weeks and to study crossover participants (prednisone to vamorolone; placebo to vamorolone).

A total of 121 participants with DMD were randomized. Vamorolone at a dose of 6 mg/kg/d showed maintenance of improvement for all motor outcomes to week 48 (e.g., for primary outcome, time to stand from supine [TTSTAND] velocity, week 24 least squares mean [LSM] [SE] 0.052 [0.0130] rises/s vs week 48 LSM [SE] 0.0446 [0.0138]). After 48 weeks, vamorolone at a dose of 2 mg/kg/d showed similar improvements as 6 mg/kg/d for North Star Ambulatory Assessment (NSAA) (vamorolone 6 mg/kg/d–vamorolone 2 mg/kg/d LSM [SE] 0.49 [1.14]; 95% CI −1.80 to 2.78, p = 0.67), but less improvement for other motor outcomes. The placebo to vamorolone 6 mg/kg/d group showed rapid improvements after 20 weeks of treatment approaching benefit seen with 48-week 6 mg/kg/d of vamorolone treatment for TTSTAND, time to run/walk 10 m, and NSAA. There was significant improvement in linear growth after crossover in the prednisone to vamorolone 6 mg/kg/d group, and rapid reversal of prednisone-induced decline in bone turnover biomarkers in both crossover groups. There was an increase in BMI after 24 weeks of treatment that then stabilized for both vamorolone groups.

Improvements of motor outcomes seen with 6 mg/kg/d of vamorolone at 24 weeks of treatment were maintained to 48 weeks of treatment. Vamorolone at a dose of 6 mg/kg/d showed better maintenance of effect compared with vamorolone at a dose of 2 mg/kg/d for most (3/5) motor outcomes. Bone morbidities of prednisone (stunting of growth and declines in serum bone biomarkers) were reversed when treatment transitioned to vamorolone.”

AGAMREE is the first and only medicinal product for DMD to have received full approval in the EU and, following approval in the U.S. last October and in the UK in January, it is the first authorized treatment for patients with the disease in all three territories.

References:
[1]   Applicable drug labeling: Summary of Product Characteristics (SmPC). English. German.
[2]   Dang UJ et al. (2024) Neurology 2024;102:e208112. doi.org/10.1212/WNL.0000000000208112. Link.
[3]    Guglieri M et al (2022). JAMA Neurol. 2022;79(10):1005-1014. doi:10.1001/jamaneurol.2022.2480. Link.
[4]    Liu X et al (2020). Proc Natl Acad Sci USA 117:24285-24293
[5]    Heier CR et al (2019). Life Science Alliance DOI: 10.26508
[6]    Ward et al., WMS 2022, FP.27 - Poster 71. Link.
[7]   Hasham et al., MDA 2022 Poster presentation. Link.