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Review

An Overview of the Efficacy and Safety of Ozanimod for the Treatment of Relapsing Multiple Sclerosis

, , & ORCID Icon
Pages 1993-2004 | Published online: 11 May 2021

References

  • DoshiA, ChatawayJ. Multiple sclerosis, a treatable disease. Clin Med (Lond). 2016;16(Suppl 6):s53–s59. doi:10.7861/clinmedicine.16-6-s5327956442
  • OhJ, Vidal-JordanaA, MontalbanX. Multiple sclerosis: clinical aspects. Curr Opin Neurol. 2018;31(6):752–759. doi:10.1097/WCO.000000000000062230300239
  • ObinataH, HlaT. Sphingosine 1-phosphate and inflammation. Int Immunol. 2019;31(9):617–625. doi:10.1093/intimm/dxz03731049553
  • ChaudhryBZ, CohenJA, ConwayDS. Sphingosine 1-Phosphate receptor modulators for the treatment of multiple sclerosis. Neurotherapeutics. 2017;14(4):859–873. doi:10.1007/s13311-017-0565-428812220
  • RascheL, PaulF. Ozanimod for the treatment of relapsing remitting multiple sclerosis. Expert Opin Pharmacother. 2018;19(18):2073–2086. doi:10.1080/14656566.2018.154059230407868
  • ChibaK, YanagawaY, MasubuchiY, et al. FTY720, a novel immunosuppressant, induces sequestration of circulating mature lymphocytes by acceleration of lymphocyte homing in rats. I. FTY720 selectively decreases the number of circulating mature lymphocytes by acceleration of lymphocyte homing. J Immunol. 1998;160(10):5037–5044.9590253
  • CohanS, LucassenE, SmootK, BrinkJ, ChenC. Sphingosine-1-Phosphate: its pharmacological regulation and the treatment of multiple sclerosis: a review article. Biomedicines. 2020;8(7):227. doi:10.3390/biomedicines8070227
  • KapposL, AntelJ, ComiG, et al. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med. 2006;355(11):1124–1140. doi:10.1056/NEJMoa05264316971719
  • NovgorodovAS, El-AlwaniM, BielawskiJ, ObeidLM, GudzTI. Activation of sphingosine-1-phosphate receptor S1P5 inhibits oligodendrocyte progenitor migration. FASEB J. 2007;21(7):1503–1514. doi:10.1096/fj.06-7420com17255471
  • JaillardC, HarrisonS, StankoffB, et al. Edg8/S1P5: an oligodendroglial receptor with dual function on process retraction and cell survival. J Neurosci. 2005;25(6):1459–1469. doi:10.1523/JNEUROSCI.4645-04.200515703400
  • Van DoornR, Lopes PinheiroMA, KooijG, et al. Sphingosine 1-phosphate receptor 5 mediates the immune quiescence of the human brain endothelial barrier. J Neuroinflammation. 2012;9:133. doi:10.1186/1742-2094-9-13322715976
  • UrbanoM, GuerreroM, RosenH, RobertsE. Modulators of the Sphingosine 1-phosphate receptor 1. Bioorg Med Chem Lett. 2013;23(23):6377–6389. doi:10.1016/j.bmcl.2013.09.05824125884
  • GoldR, ComiG, PalaceJ, et al. Assessment of cardiac safety during fingolimod treatment initiation in a real-world relapsing multiple sclerosis population: a Phase 3b, open-label study. J Neurol. 2014;261(2):267–276. doi:10.1007/s00415-013-7115-824221641
  • GergelyP, Nuesslein-HildesheimB, GueriniD, et al. The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate. Br J Pharmacol. 2012;167(5):1035–1047. doi:10.1111/j.1476-5381.2012.02061.x22646698
  • SelmajK, LiDK, HartungHP, et al. Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study [published correction appears in Lancet Neurol. 2013 Sep;12(9):846]. Lancet Neurol. 2013;12(8):756–767. doi:10.1016/S1474-4422(13)70102-923764350
  • KapposL, LiDK, StüveO, et al. Safety and Efficacy of Siponimod (BAF312) in patients with relapsing-remitting multiple sclerosis: dose-blinded, randomized extension of the phase 2 BOLD Study. JAMA Neurol. 2016;73(9):1089–1098. doi:10.1001/jamaneurol.2016.145127380540
  • KapposL, Bar-OrA, CreeBAC, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study [published correction appears in Lancet. 2018 Nov 17;392(10160):2170]. Lancet. 2018;391(10127):1263–1273. doi:10.1016/S0140-6736(18)30475-629576505
  • DumitrescuL, ConstantinescuCS, TanasescuR. Siponimod for the treatment of secondary progressive multiple sclerosis. Expert Opin Pharmacother. 2019;20(2):143–150. doi:10.1080/14656566.2018.155136330517042
  • U.S. Food and Drug Administration (FDA). FDA approves new oral drug to treat multiple sclerosis; 2021. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-new-oral-drug-treat-multiple-sclerosis. Accessed 326, 2019.
  • European Medicines Agency (EMA). MayzentEPAR; 2021. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/mayzent. Accessed 1112, 2019.
  • OlssonT, BosterA, FernándezÓ, et al. Oral ponesimod in relapsing-remitting multiple sclerosis: a randomised phase II trial. J Neurol Neurosurg Psychiatry. 2014;85(11):1198–1208. doi:10.1136/jnnp-2013-30728224659797
  • KapposL, FoxRJ, BurcklenM, et al. Ponesimod compared with teriflunomide in patients with relapsing multiple sclerosis in the active-comparator Phase 3 OPTIMUM Study: a Randomized Clinical Trial [published online ahead of print, 2021 Mar 29]. JAMA Neurol. 2021. doi:10.1001/jamaneurol.2021.0405
  • European Medicines Agency (EMA). Ponvory; 2021. Available from: https://www.ema.europa.eu/en/medicines/human/summaries-opinion/ponvory. Accessed 325, 2021.
  • ScottFL, ClemonsB, BrooksJ, et al. Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1) and receptor-5 (S1P5) agonist with autoimmune disease-modifying activity. Br J Pharmacol. 2016;173(11):1778–1792. doi:10.1111/bph.1347626990079
  • TranJQ, HartungJP, PeachRJ, et al. Results from the first-in-human study with ozanimod, a novel, selective sphingosine-1-Phosphate receptor modulator. J Clin Pharmacol. 2017;57(8):988–996. doi:10.1002/jcph.88728398597
  • ECTRIMS Online Library. Taylor MeadowsK Ozanimod (RPC1063) is potentially neuroprotective through direct CNS effects. 10/27/17; 200838; P118310/27/17; 200838; P1183. Available from: https://onlinelibrary.ectrims-congress.eu/ectrims/2017/ACTRIMS-ECTRIMS2017/200838/kristen.r.taylor.meadows.ozanimod.28rpc106329.is.potentially.neuroprotective.html. Accessed 423, 2021.
  • Taylor MeadowsK, ScottF, VillescazC, et al. Ozanimod (RPC1063) reduces the plasma biomarker neurofilament light chain in preclinical rodent models of multiple sclerosis. ECTRIMS Online Library; 2021. Available from: https://onlinelibrary.ectrims-congress.eu/ectrims/2017/ACTRIMS-ECTRIMS2017/199629/kristen.r.taylor.meadows.ozanimod.(rpc1063).reduces.the.plasma.biomarker.html. Accessed 423, 2021.
  • Taylor MeadowsK Ozanimod (RPC1063) is potentially neuroprotective through direct CNS effects. ECTRIMS online library; 2021. Available from: https://onlinelibrary.ectrims-congress.eu/ectrims/2017/ACTRIMS-ECTRIMS2017/200838/kristen.r.taylor.meadows.ozanimod.28rpc106329.is.potentially.neuroprotective.html. Accessed 423, 2021.
  • MusellaA, GentileA, GuadalupiL, et al. Central modulation of selective sphingosine-1-Phosphate receptor 1 ameliorates experimental multiple sclerosis. Cells. 2020;9(5):1290. doi:10.3390/cells9051290
  • CreeBAC, MaresJ, HartungHP. Current therapeutic landscape in multiple sclerosis: an evolving treatment paradigm [published correction appears in Curr Opin Neurol. 2019 Oct;32(5):782]. Curr Opin Neurol. 2019;32(3):365–377. doi:10.1097/WCO.000000000000070030985372
  • Celgene Corporation. Zeposia (ozanimod) capsules: US prescription information 2020; 2021. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209899s000lbl.pdf. Accessed 423, 2021.
  • TranJQ, HartungJP, TompkinsCA, FrohnaPA. Effects of high- and low-fat meals on the pharmacokinetics of ozanimod, a novel sphingosine-1-Phosphate receptor modulator. Clin Pharmacol Drug Dev. 2018;7(6):634–640. doi:10.1002/cpdd.40929125718
  • ZEPOSIA (Ozanimod) (Package Insert). Celgene Corporation: summit, NJ, USA; 2021. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209899s000lbl.pdf. Accessed 423, 2021.
  • HarrisS, TranJQ, SouthworthH, SpencerCM, CreeBAC, ZamvilSS. Effect of the sphingosine-1-phosphate receptor modulator ozanimod on leukocyte subtypes in relapsing MS. Neurol Neuroimmunol Neuroinflamm. 2020;7(5):e839. doi:10.1212/NXI.000000000000083932737072
  • CohenJA, ArnoldDL, ComiG, et al. Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016;15(4):373–381. doi:10.1016/S1474-4422(16)00018-126879276
  • CohenJA, ComiG, SelmajKW, et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, randomised, 24-month, phase 3 trial. Lancet Neurol. 2019;18(11):1021–1033. doi:10.1016/S1474-4422(19)30238-831492652
  • ComiG, KapposL, SelmajKW, et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial. Lancet Neurol. 2019;18(11):1009–1020. doi:10.1016/S1474-4422(19)30239-X31492651
  • DeLucaJ, SchipplingS, MontalbanX, et al. Effect of ozanimod on symbol digit modalities test performance in relapsing MS [published online ahead of print, 2020 Dec 10]. Mult Scler Relat Disord. 2020;48:102673. doi:10.1016/j.msard.2020.10267333454584
  • ECTRIMS Online Library. SteinmanL. 09/12/19; 278233; P1031. Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis: results from the DAYBREAK Open-Label Extension Study; 2021. Available from: https://onlinelibrary.ectrims-congress.eu/ectrims/2019/stockholm/278233/lawrence.steinman.long-term.safety.and.efficacy.of.ozanimod.in.relapsing.html. Accessed 423, 2021.
  • The ENLIGHTEN study; 2021. Available from: https://clinicaltrials.gov/ct2/show/NCT03261453. Accessed 423, 2021.
  • SwallowE, Patterson-LombaO, YinL, et al. Comparative safety and efficacy of ozanimod versus fingolimod for relapsing multiple sclerosis. J Comp Eff Res. 2020;9(4):275–285. doi:10.2217/cer-2019-016931948278
  • TongJ, ZouQ, ChenY, et al. Efficacy and acceptability of the S1P receptor in the treatment of multiple sclerosis: a meta-analysis [published online ahead of print, 2021 Feb 1] [published correction appears in Neurol Sci. 2021 Mar 19;:]. Neurol Sci. 2021. doi:10.1007/s10072-021-05049-w
  • LuG, AdesAE. Combination of direct and indirect evidence in mixed treatment comparisons. Stat Med. 2004;23(20):3105–3124. doi:10.1002/sim.187515449338
  • KapposL, ArnoldDL, Bar-OrA, et al. Safety and efficacy of amiselimod in relapsing multiple sclerosis (MOMENTUM): a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2016;15(11):1148–1159. doi:10.1016/S1474-4422(16)30192-227543447
  • KapposL, ArnoldDL, Bar-OrA, et al. Two-year results from a phase 2 extension study of oral amiselimod in relapsing multiple sclerosis. Mult Scler. 2018;24(12):1605–1616. doi:10.1177/135245851772834328911260
  • HakikiB, PortaccioE, GianniniM, RazzoliniL, PastòL, AmatoMP. Withdrawal of fingolimod treatment for relapsing-remitting multiple sclerosis: report of six cases. Mult Scler. 2012;18(11):1636–1639. doi:10.1177/135245851245477322829326
  • BergerB, BaumgartnerA, RauerS, et al. Severe disease reactivation in four patients with relapsing-remitting multiple sclerosis after fingolimod cessation. J Neuroimmunol. 2015;282:118–122. doi:10.1016/j.jneuroim.2015.03.02225903738
  • GhezziA, RoccaMA, BaronciniD, et al. Disease reac- tivation after fingolimod discontinuation in two multiple sclerosis patients. J Neurol. 2013;260:327–329. doi:10.1007/s00415-012-6744-723161460
  • HatcherSE, WaubantE, NourbakhshB, Crabtree-HartmanE, GravesJS. Rebound syndrome in patients with multiple sclerosis after cessation of fingolimod treatment. JAMA Neurol. 2016;73(7):790–794. doi:10.1001/jamaneurol.2016.082627135594
  • FrauJ, SormaniMP, SignoriA, et al. Clinical activity after fingolimod cessation: disease reactivation or rebound? Eur J Neurol. 2018;25(10):1270–1275. doi:10.1111/ene.1369429851435
  • SongZY, YamasakiR, KawanoY, et al. Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod. PLoS One. 2015;10(4):e0124923. doi:10.1371/journal.pone.012492325919001
  • Al-ZaqriN, PooventhiranT, Jagadeeswara RaoD, et al. Structure, conformational dynamics, quantum mechanical studies and potential biological activity analysis of multiple sclerosis medicine ozanimod. J Mol Struc. 2021;1227:e129685. doi:10.1016/j.molstruc.2020.129685
  • Taylor MeadowsKR, SteinbergMW, ClemonsB, et al. Ozanimod (RPC1063), a selective S1PR1 and S1PR5 modulator, reduces chronic inflammation and alleviates kidney pathology in murine systemic lupus erythematosus. PLoS One. 2018;13(4):e0193236. doi:10.1371/journal.pone.019323629608575
  • SandbornWJ, FeaganBG, WolfDC, et al. Ozanimod induction and maintenance treatment for ulcerative colitis. N Engl J Med. 2016;374(18):1754–1762. doi:10.1056/NEJMoa151324827144850
  • SandbornWJ, FeaganBG, HanauerS. et al. Long-term efficacy and safety of ozanimod in moderate-to-severe ulcerative colitis: results from the open-label extension of the randomized, Phase 2 Touchstone Study [published online ahead of print, 2021 Jan 13]. J Crohns Colitis;2021. jjab012. doi:10.1093/ecco-jcc/jjab01233438008
  • FeaganBG, SandbornWJ, DaneseS, et al. Ozanimod induction therapy for patients with moderate to severe Crohn’s disease: a single-arm, phase 2, prospective observer-blinded endpoint study. Lancet Gastroenterol Hepatol. 2020;5(9):819–828. doi:10.1016/S2468-1253(20)30188-632553149
  • LambYN. Ozanimod: first Approval. Drugs. 2020;80(8):841–848. doi:10.1007/s40265-020-01319-732385738
  • Pérez-JeldresT, TylerCJ, BoyerJD, et al. Targeting cytokine signaling and lymphocyte traffic via small molecules in inflammatory bowel disease: JAK Inhibitors and S1PR Agonists. Front Pharmacol. 2019;10:212. doi:10.3389/fphar.2019.0021230930775
  • O’SullivanS, DevKK. Sphingosine-1-phosphate receptor therapies: advances in clinical trials for CNS-related diseases. Neuropharmacology. 2017;113(Pt B):597–607. doi:10.1016/j.neuropharm.2016.11.00627825807
  • PotenzaRL, De SimoneR, ArmidaM, et al. Fingolimod: a disease-modifier drug in a mouse model of amyotrophic lateral sclerosis. Neurotherapeutics. 2016;13(4):918–927. doi:10.1007/s13311-016-0462-227456702
  • DeograciasR, YazdaniM, DekkersMP, et al. Fingolimod, a sphingosine-1 phosphate receptor modulator, increases BDNF levels and improves symptoms of a mouse model of Rett syndrome. Proc Natl Acad Sci U S A. 2012;109(35):14230–14235. doi:10.1073/pnas.120609310922891354
  • LiW, XuH, TestaiFD, Mechanism of action and clinical potential of fingolimod for the treatment of stroke. Front Neurol. 2016;7:139. doi:10.3389/fneur.2016.0013927617002
  • Estrada-BernalA, PalanichamyK, Ray ChaudhuryA, Van BrocklynJR. Induction of brain tumor stem cell apoptosis by FTY720: a potential therapeutic agent for glioblastoma. Neuro Oncol. 2012;14(4):405–415. doi:10.1093/neuonc/nos00522351749
  • Di PardoA, AmicoE, FavellatoM, et al. FTY720 (fingolimod) is a neuroprotective and disease-modifying agent in cellular and mouse models of Huntington disease. Hum Mol Genet. 2014;23(9):2251–2265. doi:10.1093/hmg/ddt61524301680
  • GaoF, LiuY, LiX, WangY, WeiD, JiangW. Fingolimod (FTY720) inhibits neuroinflammation and attenuates spontaneous convulsions in lithium-pilocarpine induced status epilepticus in rat model. Pharmacol Biochem Behav. 2012;103(2):187–196. doi:10.1016/j.pbb.2012.08.02522960129
  • ZhengC, KarI, ChenCK, et al. Multiple sclerosis disease-modifying therapy and the COVID-19 Pandemic: implications on the Risk of Infection and Future Vaccination. CNS Drugs. 2020;34(9):879–896. doi:10.1007/s40263-020-00756-y32780300
  • Sharifian-DorcheM, SahraianMA, FaddaG, et al. COVID-19 and disease-modifying therapies in patients with demyelinating diseases of the central nervous system: a systematic review [published online ahead of print, 2021 Jan 29]. Mult Scler Relat Disord. 2021;50:102800. doi:10.1016/j.msard.2021.10280033578206
  • LoonstraFC, HoitsmaE, van KempenZL, KillesteinJ, MostertJP. COVID-19 in multiple sclerosis: the Dutch experience. Mult Scler. 2020;26(10):1256–1260. doi:10.1177/135245852094219832662742
  • MallucciG, ZitoA, FabbroBD, BergamaschiR. Asymptomatic SARS-CoV-2 infection in two patients with multiple sclerosis treated with fingolimod. Mult Scler Relat Disord. 2020;45:102414. doi:10.1016/j.msard.2020.10241432711296
  • BolloL, GuerraT, BavaroDF, et al. Seroconversion and indolent course of COVID-19 in patients with multiple sclerosis treated with fingolimod and teriflunomide. J Neurol Sci. 2020;416:117011. doi:10.1016/j.jns.2020.11701132650143
  • BowenJD, BrinkJ, BrownTR, et al. COVID-19 in MS: initial observations from the Pacific Northwest. Neurol Neuroimmunol Neuroinflamm. 2020;7(5):e783. doi:10.1212/NXI.000000000000078332457226
  • BarzegarM, MirmosayyebO, NehzatN, et al. COVID-19 infection in a patient with multiple sclerosis treated with fingolimod. Neurol Neuroimmunol Neuroinflamm. 2020;7(4):e753. doi:10.1212/NXI.000000000000075332371550
  • FoerchC, FriedauerL, BauerB, WolfT, AdamEH. Severe COVID-19 infection in a patient with multiple sclerosis treated with fingolimod. Mult Scler Relat Disord. 2020;42:102180. doi:10.1016/j.msard.2020.10218032408155
  • Gomez-MayordomoV, Montero-EscribanoP, Matías-GuiuJA, González-GarcíaN, Porta-EtessamJ, Matías-GuiuJ. Clinical exacerbation of SARS-CoV2 infection after fingolimod withdrawal. J Med Virol. 2020;93:546–549. doi:10.1002/jmv.2627932644205
  • ParrottaE, KisterI, CharvetL, et al. COVID-19 outcomes in MS: observational study of early experience from NYU Multiple Sclerosis Comprehensive Care Center. Neurol Neuroimmunol Neuroinflamm. 2020;7(5):e835. doi:10.1212/NXI.000000000000083532646885
  • SormaniMP, De RossiN, SchiavettiI, et al. Disease-modifying therapies and coronavirus disease 2019 severity in multiple sclerosis. Ann Neurol. 2021;89:780–789. doi:10.1002/ana.2602833480077
  • U.S. Food and Drug Administration (FDA). Drug Trials Snapshots: ZEPOSIA; 2021. Available from: https://www.fda.gov/drugs/development-approval-process-drugs/drug-trials-snapshots-zeposia. Accessed 423, 2021.
  • European Medicines Agency (EMA). Zeposia; 2021. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/zeposia. Accessed 423, 2021.