Vidofludimus

Last updated

Vidofludimus
INN: Vidofludimus calcium
Vidofludimus.svg
Clinical data
Routes of
administration 		oral (tablet)
Drug class small-molecule
Legal status
Legal status
  • Investigational
Identifiers
  • 2-[[2-fluoro-4-(3-methoxyphenyl)phenyl]carbamoyl]cyclopentene-1-carboxylic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.112.872 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C20H18FNO4
Molar mass 355.365 g·mol−1
3D model (JSmol)
  • COC1=CC=CC(=C1)C2=CC(=C(C=C2)NC(=O)C3=C(CCC3)C(=O)O)F
  • InChI=1S/C20H18FNO4/c1-26-14-5-2-4-12(10-14)13-8-9-18(17(21)11-13)22-19(23)15-6-3-7-16(15)20(24)25/h2,4-5,8-11H,3,6-7H2,1H3,(H,22,23)(H,24,25)
  • Key:XPRDUGXOWVXZLL-UHFFFAOYSA-N

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]

Contents

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.
  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 102129. doi: 10.1016/j.msard.2020.102129 . PMID   32428844.
  3. ↑ Marco Meglio (2023-07-28). "Potential of Vidofludimus Calcium as a Nurr1 Activator". Neurology Live. Retrieved 2025-09-19.
  4. ↑ Lindsey Shapiro (2025-01-09). "Immunic 'on track' with MS clinical trials testing vidofludimus calcium". Multiple Sclerosis News Today (in German). Retrieved 2025-09-19.
  5. 1 2 "Vidofludimus Calcium - Immunic Therapeutics". Imux. Retrieved 2024-08-30.
  6. ↑ "Frankfurter Uniklinik testet Medikament gegen Post Covid". Frankfurter Allgemeine Zeitung (in German). 2024-09-11. Retrieved 2025-09-19.
  7. 1 2 Robert J. Fox, Heinz Wiendl, Christian Wolf, Nicola De Stefano, Johann Sellner, Viktoriia Gryb, 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. Vol. 9, no. 7. pp. 977–987. doi:10.1002/acn3.51574.
  8. 1 2 Robert J. Fox, Heinz Wiendl, Christian Wolf, Nicola De Stefano, Johann Sellner, Viktoriia Gryb, et al. (May 2024). "Safety and Dose-Response of Vidofludimus Calcium in Relapsing Multiple Sclerosis". Neurology Neuroimmunology & Neuroinflammation. Vol. 11, no. 3. doi:10.1212/NXI.0000000000200208 . Retrieved 2025-09-19.
  9. 1 2 "Immunic Announces Vidofludimus Calcium Reduced Risk of Disability Worsening by 30% in Primary Progressive Multiple Sclerosis Patients from Phase 2 CALLIPER Trial". Imux. Retrieved 2025-09-19.
  10. 1 2 Geert D'Haens, Kalina Grivcheva Stardelova, Edite Sadiku, Natallia Kizlova, Syitlana Skybalo, Yulia Shehovtsova, 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. Vol. 16, no. 3. doi:10.14309/ctg.0000000000000813.
  11. 1 2 Elizabeth J. Carey, John Eaton, Mitchell Clayton, Andrea Gossard, Sara Iqbal, Hamid Ullah, et al. (July 2022). "A pilot study of vidofludimus calcium for treatment of primary sclerosing cholangitis". Hepatology Communications. Vol. 6(7). pp. 1589–1597.
  12. 1 2 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. No. 11. pp. 2159–2176.
  13. 1 2 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. Vol. 45, no. 5. pp. 557–573. doi:10.1007/s13318-020-00623-7. PMC   7511286 .
  14. ↑ J. Vietor, C. Gege, T. Stiller, R. Busch, E. Schallmayer, H. Kohlhof, et al. (2023-05-11). "Development of a Potent Nurr1 Agonist Tool for In Vivo Applications". J Med Chem. No. 66(9). pp. 6391–6402.
  15. ↑ Lindsey Shapiro (2023-05-18). "Experimental MS therapy vidofludimus calcium triggers Nurr1 protein" . Retrieved 2025-09-19.
  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. Vol. 43. doi:10.1016/j.msard.2020.102129. PMID   32428844.
  17. 1 2 3 Shitiz Sriwastava, Mahmoud Elkhooly, Suban Amatya, Kriti Shrestha, Yusuf Kagzi, Dipika Bhatia, et al. (2024-05-15). "Recent advances in the treatment of primary and secondary progressive Multiple Sclerosis". Journal of Neuroimmunology. Vol. 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". Fierce Biotech. Retrieved 2025-09-19.
  19. ↑ "4SC, Immunic deal". BioCentury. 2016-10-03. Retrieved 2025-09-19.
  20. ↑ "Other news to note for March 31, 2021". BioWorld. 2021-03-31. Retrieved 2025-09-19.
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