Chemistry:Vidofludimus

From HandWiki

Vidofludimus is an orally administered small-molecule compound and an investigational new drug. Its calcium salt is being evaluated to treat multiple sclerosis (MS), ulcerative colitis and other chronic inflammatory and autoimmune diseases.[1] It is a nuclear receptor-related 1 (Nurr1) activator and dihydroorotate dehydrogenase (DHODH) inhibitor.[2][3] Vidofludimus is being developed by the American-German biotechnology company Immunic Therapeutics.[4]

Potential medical applications

As of 2025, vidofludimus calcium is not approved in any country and is being tested in clinical trials for the treatment of MS, including the Phase 3 ENSURE studies in relapsing multiple sclerosis (RMS), as well as for the treatment of post‑COVID syndrome (PCS).[5][6]

In addition, the investigational drug was tested in Phase 2 studies in relapsing‑remitting MS (RRMS),[7][8] progressive MS (PMS),[9] moderate to severe ulcerative colitis (UC),[10] primary sclerosing cholangitis (PSC)[11] and COVID-19,[12] as well as in Phase 1 studies in healthy volunteers.[13]

As studies have shown, the safety profile observed is similar to that of placebo.[7][8][9][10][11][12] The pharmacokinetic profile, with a terminal plasma half-life of approximately 30 hours, enables once-daily oral administration.[13]

Mechanism of action

Vidofludimus calcium acts as an activator of nuclear receptor-related 1 (Nurr1),[14] a neuroprotective transcription factor and emerging target for neurodegenerative diseases. Activation of Nurr1 is associated with neuroprotective effects by acting on microglia, astrocytes, and neurons. In microglia and astrocytes, Nurr1 activation leads to a reduction in pro-inflammatory cytokines and blocks the production of direct neurotoxic agents such as reactive oxygen species and nitric oxide. Increased Nurr1 activity in neurons promotes neuronal survival and differentiation, as well as improved neurotransmission. Therefore, activation of Nurr1 by vidofludimus calcium could reduce or halt neurodegeneration and the progression of disability in patients suffering from MS and other degenerative diseases.[15]

In addition to its effects as a Nurr1 activator, vidofludimus calcium is also an inhibitor of dihydroorotate dehydrogenase (DHODH),[16][17] a mitochondrial key enzyme required for pyrimidine de novo biosynthesis. In contrast to resting lymphocytes, active and rapidly proliferating lymphocytes rely on this enzyme to meet their demand for pyrimidines. To counteract an activated and pathogenic lymphocyte population, DHODH blockade is of clinical interest: the activated lymphocytes undergo metabolic stress, which subsequently induces apoptosis of the activated immune cells.[17]

Pharmaceutical formulation

Vidofludimus calcium is formulated as an oral tablet. Current dose strengths used in clinical studies are 30 mg and 45 mg.[5][17]

Medical history

The company behind vidofludimus calcium, Immunic Therapeutics, was founded in 2016 in Planegg-Martinsried, Germany. In September 2016, Immunic Therapeutics received a Series A funding of €17.5 million. With this money, Immunic Therapeutics acquired immunology programs from company 4SC.[18][19] In March 2021, the outstanding royalties with 4SC were settled, resulting in vidofludimus calcium being fully owned by Immunic.[20]

References

  1. ↑ "Vidofludimus calcium — Immunic". AdisInsight. Springer Nature Switzerland AG. https://adisinsight.springer.com/drugs/800048014. 
  2. ↑ A. Muehler; E. Peelen; H. Kohlhof; M. Gröppel; D. Vitt (August 2020). "Vidofludimus calcium, a next generation DHODH inhibitor for the Treatment of relapsing-remitting multiple sclerosis". Multiple Sclerosis and Related Disorders 43. doi:10.1016/j.msard.2020.102129. PMID 32428844. 
  3. ↑ Marco Meglio (2023-07-28). "Potential of Vidofludimus Calcium as a Nurr1 Activator" (in en). Neurology Live. https://www.neurologylive.com/view/potential-vidofludimus-calcium-nurr1-activator. 
  4. ↑ Lindsey Shapiro (2025-01-09). "Immunic 'on track' with MS clinical trials testing vidofludimus calcium" (in de). Multiple Sclerosis News Today. https://multiplesclerosisnewstoday.com/news-posts/2025/01/09/immunic-ms-clinical-trials-vidofludimus-calcium-progressing/. 
  5. ↑ 5.0 5.1 "Vidofludimus Calcium - Immunic Therapeutics" (in en). Imux. https://imux.com/pipeline/imu-838/. 
  6. ↑ "Frankfurter Uniklinik testet Medikament gegen Post Covid" (in de). Frankfurter Allgemeine Zeitung. 2024-09-11. https://www.faz.net/aktuell/rhein-main/frankfurt/frankfurter-uniklinik-testet-medikament-gegen-post-covid-19973127.html. 
  7. ↑ 7.0 7.1 Robert J. Fox; Heinz Wiendl; Christian Wolf; Nicola De Stefano; Johann Sellner; Viktoriia Gryb; Konrad Rejdak; Plamen Stoyanov Bozhinov et al. (2022). "A double-blind, randomized, placebo-controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium in relapsing-remitting multiple sclerosis". Annals of Clinical and Translational Neurology 9 (7): pp. 977–987. doi:10.1002/acn3.51574. 
  8. ↑ 8.0 8.1 Robert J. Fox; Heinz Wiendl; Christian Wolf; Nicola De Stefano; Johann Sellner; Viktoriia Gryb; Konrad Rejdak; Plamen S. Bozhinov et al. (May 2024). "Safety and Dose-Response of Vidofludimus Calcium in Relapsing Multiple Sclerosis". Neurology Neuroimmunology & Neuroinflammation 11 (3). doi:10.1212/NXI.0000000000200208. https://www.neurology.org/doi/10.1212/NXI.0000000000200208. 
  9. ↑ 9.0 9.1 "Immunic Announces Vidofludimus Calcium Reduced Risk of Disability Worsening by 30% in Primary Progressive Multiple Sclerosis Patients from Phase 2 CALLIPER Trial" (in en). Imux. https://imux.com/immunic-announces-vidofludimus-calcium-reduced-risk-of-disability-worsening-by-30-in-primary-progressive-multiple-sclerosis-patients-from-phase-2-calliper-trial/. 
  10. ↑ 10.0 10.1 Geert D'Haens; Kalina Grivcheva Stardelova; Edite Sadiku; Natallia Kizlova; Syitlana Skybalo; Yulia Shehovtsova; Mirela Abramescu; Daniel Vitt et al. (March 2025). "Vidofludimus Calcium in Patients With Moderate-to-Severe Ulcerative Colitis: A Randomized, Placebo-Controlled, Phase 2 Trial". Clinical and Translational Gastroenterology 16 (3). doi:10.14309/ctg.0000000000000813. 
  11. ↑ 11.0 11.1 Elizabeth J. Carey; John Eaton; Mitchell Clayton; Andrea Gossard; Sara Iqbal; Hamid Ullah; Nan Zhang; Richard Butterfield et al. (July 2022). "A pilot study of vidofludimus calcium for treatment of primary sclerosing cholangitis.". Hepatology Communications 6 (7): pp. 1589–1597. 
  12. ↑ 12.0 12.1 M.J.G.T. Vehreschild; P. Atanasov; K. Yurko (2022). "Safety and Efficacy of Vidofludimus Calcium in Patients Hospitalized with COVID-19: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial.". Infect Dis Ther (11): pp. 2159–2176. 
  13. ↑ 13.0 13.1 Andreas Muehler; Hella Kohlhof; Manfred Groeppel; Daniel Vitt (2020-10-01). "Safety, Tolerability and Pharmacokinetics of Vidofludimus calcium (IMU-838) After Single and Multiple Ascending Oral Doses in Healthy Male Subjects". European Journal of Drug Metabolism and Pharmacokinetics 45 (5): pp. 557–573. doi:10.1007/s13318-020-00623-7. 
  14. ↑ J. Vietor; C. Gege; T. Stiller; R. Busch; E. Schallmayer; H. Kohlhof; G. Höfner; J. Pabel et al. (2023-05-11). "Development of a Potent Nurr1 Agonist Tool for In Vivo Applications.". J Med Chem 66 (9): pp. 6391–6402. 
  15. ↑ Lindsey Shapiro (2023-05-18). "Experimental MS therapy vidofludimus calcium triggers Nurr1 protein" (in en). https://multiplesclerosisnewstoday.com/news-posts/potential-ms-therapy-vidofludimus-calcium-triggers-nurr1-protein. 
  16. ↑ Andreas Muehler; Evelyn Peelen; Hella Kohlhof; Manfred Gröppel; Daniel Vitt (2020-08-01). "Vidofludimus calcium, a next generation DHODH inhibitor for the Treatment of relapsing-remitting multiple sclerosis". Multiple Sclerosis and Related Disorders 43. doi:10.1016/j.msard.2020.102129. PMID 32428844. 
  17. ↑ 17.0 17.1 17.2 Shitiz Sriwastava; Mahmoud Elkhooly; Suban Amatya; Kriti Shrestha; Yusuf Kagzi; Dipika Bhatia; Rajesh Gupta; Shruti Jaiswal et al. (2024-05-15). "Recent advances in the treatment of primary and secondary progressive Multiple Sclerosis" (in en). Journal of Neuroimmunology 390. doi:10.1016/j.jneuroim.2024.578315. PMID 38554666. 
  18. ↑ Nick Paul Taylor (2016-09-28). "Immunic wraps up €17.5M Series A, buys immunology programs from 4SC" (in en). Fierce Biotech. https://www.fiercebiotech.com/biotech/immunic-wraps-up-eu17-5m-series-a-buys-immunology-programs-from-4sc. 
  19. ↑ "4SC, Immunic deal". BioCentury. 2016-10-03. https://www.biocentury.com/article/280881/4sc-immunic-deal. 
  20. ↑ "Other news to note for March 31, 2021" (in en). BioWorld. 2021-03-31. https://www.bioworld.com/articles/505380-other-news-to-note-for-march-31-2021?v=preview. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Vidofludimus&oldid=4038223"