Vamorolone – a corticosteroid approved by global regulators for the treatment of Duchenne muscular dystrophy. Literature review

Cover Page

Cite item

Full Text

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked hereditary disease that manifests in early childhood and progresses with age, leading to loss of mobility and respiratory and cardiac failure. The globally recognized gold standard for DMD treatment is corticosteroids. However, until recently, only deflazacort (Emflaza) had received approval from the U.S. Food and Drug Administration (FDA) for the indication of DMD. All other drugs in this group were used off-label. At the end of 2023, the FDA, followed by the European Medicines Agency (EMA), registered another drug from the corticosteroid group – vamorolone (Agamree). In 2024, vamorolone received approval in the United Kingdom and China. Thus, all leading global regulators currently recognize vamorolone as a corticosteroids for the treatment of DMD.

About the authors

D. V. Vlodavets

Scientific Research Clinical Institute of Pediatrics and Pediatrics Surgery named after Acad.Yu.E. Veltischev, N.I. Pirogov Russian
National Research Medical University, Ministry of Health of Russia

Author for correspondence.
Email: mityaus@gmail.com
ORCID iD: 0000-0003-2635-2752

Dmitriy Vladimirovich Vlodavets 

2 Taldomskaya St., Moscow 125412

Russian Federation

S. B. Artemyeva

Scientific Research Clinical Institute of Pediatrics and Pediatrics Surgery named after Acad.Yu.E. Veltischev, N.I. Pirogov Russian
National Research Medical University, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-8876-7462

2 Taldomskaya St., Moscow 125412

Russian Federation

E. V. Tozliyan

Scientific Research Clinical Institute of Pediatrics and Pediatrics Surgery named after Acad.Yu.E. Veltischev, N.I. Pirogov Russian
National Research Medical University, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-4858-9251

2 Taldomskaya St., Moscow 125412

Russian Federation

A. K. Shulchenko

A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia

Email: fake@neicon.ru
ORCID iD: 0009-0001-2218-9874

Build. 1, 96 Prospekt Vernadskogo, Moscow 119571

Russian Federation

References

  1. Clinical guidelines “Progressive Duchenne muscular dystrophy. Progressive Becker muscular dystrophy”. 2023. (In Russ.).
  2. General characteristics of the medicinal product for medical use Viltepso, RU LP-No.(006482)-(RG-RU) dated 7 August, 2024. (In Russ.).
  3. General characteristics of the medicinal product for medical use Translarna, RU LP-006596 dated 24 November, 2020. (In Russ.).
  4. Ahmet A., Tobin R., Dang U.J. et al. Adrenal suppression from vamorolone and prednisone in Duchenne muscular dystrophy: Results from the phase 2b clinical trial. J Clin Endocrinol Metab 2025;110(2):334–44. doi: 10.1210/clinem/dgae521
  5. Angelini C., Peterle E. Old and new therapeutic developments in steroid treatment in Duchenne muscular dystrophy. Acta Myol 2012;31(1):9–15.
  6. Bello L., Gordish-Dressman H., Morgenroth L.P. et al. Prednisone/ prednisolone and deflazacort regimens in the CINRG Duchenne Natural History Study. Neurology 2015;85:1048–55.
  7. Bez Batti Angulski A., Hosny N., Cohen H. et al. Duchenne muscular dystrophy: Disease mechanism and therapeutic strategies. Front Physiol 2023;14:1183101. doi: 10.3389/fphys.2023.1183101
  8. Birnkrant D.J., Bushby K., Bann C.M. et al. Diagnosis and management of Duchenne muscular dystrophy, part 3: Primary care, emergency management, psychosocial care, and transitions of care across the lifespan. Lancet Neurol 2018;17(5):445–55. doi: 10.1016/S1474-4422(18)30026-7
  9. Blake D.J., Weir A., Newey S.E. et al. function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiol Rev.2002;82(2):291–329. doi: 10.1152/physrev.00028.2001
  10. Buckon C., Sienko S., Bagley A. et al. Can quantitative muscle strength and functional motor ability differentiate the influence of age and corticosteroids in ambulatory boys with Duchenne muscular dystrophy? PLoS Curr 2016. doi: 10.1371/currents.md. 1ced64dff945f8958221fddcd4ee60b0
  11. Crastin A., Shanker A., Sagmeister M.S. et al. Vamorolone: A novel metabolism resistant steroid that suppresses joint destruction in chronic polyarthritis with reduced systemic side effects. Rheumatology (Oxford) 2025:keaf129. doi: 10.1093/rheumatology/keaf129
  12. Dang U.J., Damsker J.M., Guglieri M. et al. Efficacy and safety of vamorolone over 48 weeks in boys with Duchenne muscular dystrophy: A randomized controlled trial. Neurology 2024;102(5):e208112. doi: 10.1212/WNL.0000000000208112
  13. Duan D., Goemans N., Takeda S. et al. Duchenne muscular dystrophy. Nat Rev Dis Primers 2021;7(1):13. doi: 10.1038/s41572-021-00248-3
  14. Elhalag R.H., Motawea K.R., Talat N.E. et al. Efficacy of vamorolone in treatment of Duchene muscle dystrophy: A metaanalysis. Front Neurol 2023;14:1107474. doi: 10.3389/fneur.2023.1107474
  15. Exon 45 Skipping: Duchenne Muscular Dystrophy (DMD) | Amondys 45. Available at: https://www.amondys45.com.
  16. EXONDYS 51 (eteplirsen) | Treatment of Duchenne Muscular Dystrophy. Available at: https://www.exondys51.com.
  17. Gao Q.Q., McNally E.M. The dystrophin complex: Structure, function and implications for therapy. Compr Physiol 2015;5(3):1223–39. doi: 10.1002/cphy.c140048
  18. Guglieri M., Bushby K., McDermott M.P. et al. Effect of different c orticosteroid dosing regimens on clinical outcomes in boys with Duchenne muscular dystrophy: A randomized clinical trial. JAMA 2022;327(15):1456–68. doi: 10.1001/jama.2022.4315
  19. Guglieri M., Clemens P.R., Perlman S.J. et al. Efficacy and safety of vamorolone vs placebo and prednisone among boys with Duchenne muscular dystrophy: A randomized clinical trial. JAMA Neurol 2022,1;79(10):1005–14. doi: 10.1001/jamaneurol.2022.2480
  20. Heier C.R., Damsker J.M., Yu Q. et al. VBP15, a novel anti-inflammatory and membrane-stabilizer, improves muscular dystrophy without side effects. EMBO Mol Med 2013;5(10): 1569–85. doi: 10.1002/emmm.201302621
  21. Heier C.R., Damsker J.M., Yu Q. et al. Phase IIa trial in Duchenne muscular dystrophy shows vamorolone is a first-in-class dissociative steroidal antiinflammatory drug. Pharmacol Res 2018;136:140–50. doi: 10.1016/j.phrs.2018.09.007
  22. Heier C.R., Yu Q., Fiorillo A.A. et al. Vamorolone targets dual nuclear receptors to treat inflammation and dystrophic cardiomyopathy. Life Scie Alliance 2019;2(1):e201800186.
  23. Henricson E., de Vera A., Nip K. et al. Evaluation of behavioural problems using PARS III in the VISION-DMD study of vamorolone vs prednisone in Duchenne muscular dystrophy (DMD). Available at: https://www.santhera.com/assets/files/ content/scientific-literature/EAN-Behaviour.pdf.
  24. Hiscott J., Marois J., Garoufalis J. et al. Characterization of a functional NF-κB site in the human interleukin 1β promoter: Evidence for a positive autoregulatory loop. Mol Cell Biol 1993;13(10):6231–40. doi: 10.1128/mcb.13.10.6231-6240.1993
  25. Hoffman E.P., Riddle V., Siegler M.A. et al. Phase 1 trial of vamorolone, a first-in-class steroid, shows improvements in side effects via biomarkers bridged to clinical outcomes. Steroids 2018;134:43–52. doi: 10.1016/j.steroids.2018.02.010
  26. Hoffman E. Vamorolone: Clinical stage first dissociative steroidal anti-inflammatory. 2018. Available at: https://www.parentprojectmd.org/wp-content/uploads/2018/07/ACC18_02_200_Reveragen.pdf.
  27. Kauh E., Mixson L., Malice M.P. et al. Prednisone affects inflammation, glucose tolerance, and bone turnover within hours of treatment in healthy individuals. Eur J Endocrinol 2012;166(3):459–67. doi: 10.1530/EJE-11-0751
  28. Koeks Z., Bladen C.L., Salgado D. et al. Clinical outcomes in Duchenne muscular dystrophy: A study of 5345 patients from the TREAT-NMD DMD Global Database. J Neuromuscul Dis 2017;4(4):293–306. doi: 10.3233/JND-170280
  29. Larson C.M., Henderson R.C. Bone mineral density and fractures in boys with Duchenne muscular dystrophy. J Pediatr Orthop 2000;20(1):71–4.
  30. Libermann T.A., Baltimore D. Activation of interleukin-6 gene expression through the NF-κB transcription factor. Mol Cell Biol 1990;10(5):2327–34. doi: 10.1128/mcb.10.5.2327-2334.1990
  31. Li X., Conklin L.S., van den Anker J. et al. Exposure-response analysis of vamorolone (VBP15) in boys with Duchenne muscular dystrophy. J Clin Pharmacol 2020;60(10):1385–96. doi: 10.1002/jcph.1632
  32. Liu X., Wang Y., Gutierrez J.S. et al. Disruption of a key ligand-H-bond network drives dissociative properties in vamorolone for Duchenne muscular dystrophy treatment. Proc Natl Acad Sci USA 2020;117(39):24285–93. doi: 10.1073/pnas.2006890117
  33. Mackenzie S.J., Nicolau S., Connolly A., Mendell J. Therapeutic approaches for Duchenne muscular dystrophy: Old and new. Semin Pediatr Neurol 2021;37:100877. doi: 10.1016/j.spen.2021.100877
  34. Mah J.K., Clemens P.R., Guglieri M. et al. Efficacy and safety of vamorolone in Duchenne muscular dystrophy: A 30-month nonrandomized controlled open-label extension trial. JAMA Netw Open 2022;5(1):e2144178. doi: 10.1001/jamanetworkopen.2021.44178
  35. Manzur A.Y., Kuntzer T., Pike M., Swan A. Glucocorticoid corticosteroids for Duchenne muscular dystrophy. Cochrane Database Syst Rev 2008;1:CD003725. doi: 10.1002/14651858.CD003725.pub3
  36. Marden J.R., Freimark .J, Yao Z. et al. Real-world outcomes of long-term prednisone and deflazacort use in patients with Duchenne muscular dystrophy: Experience at a single, large care center. J Comp Eff Res 2020;9(3):177–89. doi: 10.2217/cer-2019-0170
  37. McDonald D.G., Kinali M., Gallagher A.C. et al. Fracture prevalence in Duchenne muscular dystrophy. Dev Med Child Neurol 2002;44(10):695–8. doi: 10.1017/s0012162201002778
  38. Mercuri E., Muntoni F., Osorio A.N. et al. Safety and effectiveness of ataluren: Comparison of results from the STRIDE Registry and CINRG DMD Natural History Study. J Comp Eff Res 2020;9(5):341–60. doi: 10.2217/cer-2019-0171
  39. Pane M., Fanelli L., Mazzone E.S. et al. Benefits of glucocorticoids in non-ambulant boys/men with Duchenne muscular dystrophy: A multicentric longitudinal study using the Performance of Upper Limb test. Neuromuscul Disord 2015;25(10):749–53. doi: 10.1016/j.nmd.2015.07.009
  40. Schram G., Fournier A., Leduc H. et al. All-cause mortality and cardiovascular outcomes with prophylactic steroid therapy in Duchenne muscular dystrophy. J Am Coll Cardiol 2013;61(9):948–54. doi: 10.1016/j.jacc.2012.12.008
  41. Smith E.C., Conklin L.S., Hoffman E.P. et al. Efficacy and safety of vamorolone in Duchenne muscular dystrophy: An 18-month interim analysis of a non-randomized open label extension study. PLoS Med 2020;17(9):e1003222. doi: 10.1371/journal.pmed.1003222
  42. Sreetama S.C., Chandra G., van der Meulen J.H. et al. Membrane stabilization by modified steroid offers a potential therapy for muscular dystrophy due to dysferlin deficit. Mol Ther 2018;26(9):2231–42. doi: 10.1016/j.ymthe.2018.07.021
  43. The Spine Fracture Burden in Boys with DMD Treated with the Novel Dissociative Steroid Vamorolone versus Deflazacort or Prednisone. Available at: https://www.santhera.com/assets/files/ content/scientific-literature/FP03-WMS_poster_20_August_2022.pdf.
  44. VYONDYS 53 (golodirsen) | Duchenne Muscular Dystrophy Treatment. Available at: https://www.vyondys53.com.
  45. Ward L., Jackowski S., Dang U. et al. The spine fracture burden in boys with DMD treated with the novel dissociative steroid vamorolone versus deflazacort and prednisone. Neuromuscular Disord 2022;32(Suppl 1):S42–S136. doi: 10.1016/j.nmd.2022.07.033

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c)


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 22926 от  12.01.2006.