fingolimod

{{Short description|Chemical compound}}

{{Use dmy dates|date=February 2023}}

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{{Infobox drug

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| image = Fingolimod structure.svg

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| image2 = Fingolimod-3D-balls-by-AHRLS-2011.png

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| pronounce =

| tradename = Gilenya

| Drugs.com = {{drugs.com|monograph|fingolimod-hydrochloride}}

| MedlinePlus = a611006

| DailyMedID = Fingolimod

| pregnancy_AU = D

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| routes_of_administration = By mouth

| class = Immunosuppressants

| ATC_prefix = L04

| ATC_suffix = AE01

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| legal_AU_comment = {{cite web | title=FINGOLIMOD-TEVA/TE-FINGOLIMOD (Teva Pharma Australia Pty Ltd) | website=Therapeutic Goods Administration (TGA) | date=16 February 2023 | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/fingolimod-tevate-fingolimod-teva-pharma-australia-pty-ltd | access-date=23 April 2023}}

| legal_BR =

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| legal_CA = Rx-only

| legal_CA_comment = {{cite web | title=Health product highlights 2021: Annexes of products approved in 2021 | website=Health Canada | date=3 August 2022 | url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/health-product-highlights-2021/appendices.html | access-date=25 March 2024}}

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| legal_UK = POM

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| legal_US = Rx-only

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| legal_EU = Rx-only

| legal_EU_comment = {{cite web | title=Gilenya EPAR | website=European Medicines Agency (EMA) | date=17 March 2011 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/gilenya | access-date=16 November 2024}}

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| index2_label = as HCl

| IUPHAR_ligand = 2407

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 162359-55-9

| CAS_supplemental =

| PubChem = 107970

| DrugBank_Ref = {{drugbankcite|changed|drugbank}}

| DrugBank = DB08868

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| UNII = 3QN8BYN5QF

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| KEGG2 = D04187

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| ChEBI = 63115

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| ChEMBL = 314854

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| IUPAC_name = 2-Amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol

| C=19 | H=33 | N=1 | O=2

| SMILES = CCCCCCCCC1=CC=C(C=C1)CCC(CO)(CO)N

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C19H33NO2/c1-2-3-4-5-6-7-8-17-9-11-18(12-10-17)13-14-19(20,15-21)16-22/h9-12,21-22H,2-8,13-16,20H2,1H3

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Fingolimod, sold under the brand name Gilenya, is an immunomodulating medication, used for the treatment of multiple sclerosis. Fingolimod is a sphingosine-1-phosphate receptor modulator, which sequesters lymphocytes in lymph nodes, preventing them from contributing to an autoimmune reaction. It has been reported to reduce the rate of relapses in relapsing-remitting multiple sclerosis by approximately one-half over a two-year period.{{cite journal | vauthors = Sanford M | title = Fingolimod: a review of its use in relapsing-remitting multiple sclerosis | journal = Drugs | volume = 74 | issue = 12 | pages = 1411–33 | date = August 2014 | pmid = 25063048 | doi = 10.1007/s40265-014-0264-y | s2cid = 42807019 }}

Medical uses

Fingolimod is used in the treatment of the relapsing form of multiple sclerosis. Its effect in those with primary progressive multiple sclerosis is not clear. It may also be used in chronic inflammatory demyelinating polyneuropathy.{{cite web|title=Fingolimod Hydrochloride|url=https://www.drugs.com/monograph/fingolimod-hydrochloride.html|publisher=The American Society of Health-System Pharmacists|access-date=9 August 2015}}

Adverse effects

The most common side effects of fingolimod have been head colds,{{vague|date=July 2018}} headache,{{cite web|url=https://www.uptodate.com/contents/fingolimod-drug-information?search=fingolimod&source=panel_search_result&selectedTitle=1~13&usage_type=panel&kp_tab=drug_general&display_rank=1#F10829804|title=UpToDate|website=www.uptodate.com|access-date=24 June 2019}} increased gamma-glutamyl transfer (≤15%), diarrhea (13%), nausea (13%), abdominal pain (11%) and fatigue. A few cases of skin cancer have been reported, which has also been reported in patients taking natalizumab (Tysabri), an approved multiple sclerosis drug.{{cite web|url=http://www.webmd.com/multiple-sclerosis/news/20080416/good-news-for-oral-ms-drug-fingolimod |title=Good News for Oral MS Drug Fingolimod |publisher=Webmd.com |date=16 April 2008 |access-date=30 September 2013}} Fingolimod has also been associated with potentially fatal infections, bradycardia and, in 2009, a case of hemorrhaging focal encephalitis, an inflammation of the brain with bleeding.{{cite journal | vauthors = Leypoldt F, Münchau A, Moeller F, Bester M, Gerloff C, Heesen C | title = Hemorrhaging focal encephalitis under fingolimod (FTY720) treatment: a case report | journal = Neurology | volume = 72 | issue = 11 | pages = 1022–4 | date = March 2009 | pmid = 19289744 | doi = 10.1212/01.wnl.0000344567.51394.e3 | s2cid = 8523513 }} Two people died: one due to brain herpes infection, and a second one due to herpes zoster. It is unclear whether the drug was responsible for the events.{{cite web | url=http://www.ms-uk.org/dmd?flap=6#6 | title=MS-UK | Multiple Sclerosis Information, Helpline, support, MS news and research | access-date=17 June 2014 | archive-date=19 March 2015 | archive-url=https://web.archive.org/web/20150319050553/http://www.ms-uk.org/dmd?flap=6#6 | url-status=dead }} At least 24 cases of progressive multifocal leukoencephalopathy had also occurred as of 2023.{{cite journal | vauthors = Sriwastava S, Chaudhary D, Srivastava S, Beard K, Bai X, Wen S, Khalid SH, Lisak RP | title = Progressive multifocal leukoencephalopathy and sphingosine 1-phosphate receptor modulators used in multiple sclerosis: an updated review of literature | journal = Journal of Neurology | volume = 269 | issue = 3 | pages = 1678–1687 | date = March 2022 | pmid = 34800168 | doi = 10.1007/s00415-021-10910-1 }}

Fingolimod has also been known to cause macular edema, resulting in decreased vision.{{cite journal | vauthors = Jain N, Bhatti MT | title = Fingolimod-associated macular edema: incidence, detection, and management | journal = Neurology | volume = 78 | issue = 9 | pages = 672–80 | date = February 2012 | pmid = 22371414 | doi = 10.1212/WNL.0b013e318248deea | s2cid = 11742356 }}{{cite journal |vauthors=Jain N, Bhatti MT |title=Macular Edema Associated With Fingolimod |journal=EyeNet |volume=78 |issue=9 |pages=672–80 |date=April 2012 |url=http://development.aao.org/publications/eyenet/201204/upload/Fingolimod-Associated-Macular-Edema-PDF.pdf |access-date=20 August 2015 |archive-url=https://web.archive.org/web/20160616175309/http://development.aao.org/publications/eyenet/201204/upload/Fingolimod-Associated-Macular-Edema-PDF.pdf |archive-date=16 June 2016 |url-status=dead |pmid=22371414 |doi=10.1212/WNL.0b013e318248deea |s2cid=11742356 }} Therefore, frequent surveillance eye examinations are required while taking this medication.

In the United States, fingolimod must be dispensed with a medication guide that contains important information about its uses and risks. Serious risks include slowing of the heart rate, especially after the first dose. Fingolimod may increase the risk of serious infections. Patients should be monitored for infection during treatment and for two months after discontinuation of treatment. A rare brain infection that usually leads to death or severe disability, called progressive multifocal leukoencephalopathy (PML) has been reported in patients being treated with the drug. PML cases usually occur in patients with weakened immune systems. Fingolimod can cause vision problems. It may increase the risk for swelling and narrowing of the blood vessels in the brain (posterior reversible encephalopathy syndrome). Other serious risks include respiratory problems, liver injury, increased blood pressure and skin cancer. Fingolimod may cause harm to a developing fetus; health care professionals should advise women of child-bearing age of the potential risk to the fetus and to use effective contraception.

The European Medicines Agency (EMA) stated that the multiple sclerosis medicine fingolimod (Gilenya) must not be used in pregnant women and in women able to have children who are not using effective contraception.{{cite press release | title=Updated restrictions for Gilenya: multiple sclerosis medicine not to be used in pregnancy | website=European Medicines Agency (EMA) | date=26 July 2019 | url=https://www.ema.europa.eu/en/news/updated-restrictions-gilenya-multiple-sclerosis-medicine-not-be-used-pregnancy | access-date=12 July 2020}} {{PD-notice}}

Structure and mechanism

It is derived from myriocin (ISP-1), a metabolite of the fungus Isaria sinclairii. It is a structural analogue of sphingosine and is phosphorylated by sphingosine kinases in the cell (most importantly sphingosine kinase 2).{{cite journal | vauthors = Paugh SW, Payne SG, Barbour SE, Milstien S, Spiegel S | title = The immunosuppressant FTY720 is phosphorylated by sphingosine kinase type 2 | journal = FEBS Letters | volume = 554 | issue = 1–2 | pages = 189–93 | date = November 2003 | pmid = 14596938 | doi = 10.1016/S0014-5793(03)01168-2 | s2cid = 41465940 | doi-access = | bibcode = 2003FEBSL.554..189P }}{{cite journal | vauthors = Billich A, Bornancin F, Dévay P, Mechtcheriakova D, Urtz N, Baumruker T | title = Phosphorylation of the immunomodulatory drug FTY720 by sphingosine kinases | journal = The Journal of Biological Chemistry | volume = 278 | issue = 48 | pages = 47408–15 | date = November 2003 | pmid = 13129923 | doi = 10.1074/jbc.M307687200 | doi-access = free }} [http://www.jbc.org/cgi/content/full/278/48/47408 Free full text] {{Webarchive|url=https://web.archive.org/web/20080613020334/http://www.jbc.org/cgi/content/full/278/48/47408 |date=13 June 2008 }}{{cite journal | vauthors = Sanchez T, Estrada-Hernandez T, Paik JH, Wu MT, Venkataraman K, Brinkmann V, Claffey K, Hla T | title = Phosphorylation and action of the immunomodulator FTY720 inhibits vascular endothelial cell growth factor-induced vascular permeability | journal = The Journal of Biological Chemistry | volume = 278 | issue = 47 | pages = 47281–90 | date = November 2003 | pmid = 12954648 | doi = 10.1074/jbc.M306896200 | doi-access = free }} The molecular biology of phospho-fingolimod is thought to lie in its activity at one of the five sphingosine-1-phosphate receptors, S1PR1.{{cite journal | vauthors = Hla T, Lee MJ, Ancellin N, Paik JH, Kluk MJ | title = Lysophospholipids--receptor revelations | journal = Science | volume = 294 | issue = 5548 | pages = 1875–8 | date = November 2001 | pmid = 11729304 | doi = 10.1126/science.1065323 | bibcode = 2001Sci...294.1875H | s2cid = 46727063 }} Phospho-fingolimod causes the internalization of S1P receptors, which sequesters lymphocytes in lymph nodes, preventing them from moving to the central nervous system and causing a relapse of multiple sclerosis.

The unphosphorylated moiety of fingolimod, which is the predominant form of the drug in the body, is also an active molecule. Unphosphorylated fingolimod impairs the ability of cytotoxic CD8 T cells to kill their target cells by a different mechanism, which involves the arachidonic acid pathway, which is unrelated to sphingosine phosphate receptors.{{cite journal | vauthors = Ntranos A, Hall O, Robinson DP, Grishkan IV, Schott JT, Tosi DM, Klein SL, Calabresi PA, Gocke AR | title = FTY720 impairs CD8 T-cell function independently of the sphingosine-1-phosphate pathway | journal = Journal of Neuroimmunology | volume = 270 | issue = 1–2 | pages = 13–21 | date = May 2014 | pmid = 24680062 | doi = 10.1016/j.jneuroim.2014.03.007 | s2cid = 206276944 | url = https://www.researchgate.net/publication/260760061 }} This has implications both for increasing susceptibility to viral infections as well as enhancing therapeutic efficacy in multiple sclerosis.

Additionally, fingolimod shifts macrophages to an anti-inflammatory M2 phenotype. It modulates their proliferation, morphology, and cytokine release via inhibition of the transient receptor potential cation channel, subfamily M, member 7. (TRPM7).{{cite journal | vauthors = Schilling T, Miralles F, Eder C | title = TRPM7 regulates proliferation and polarisation of macrophages | journal = Journal of Cell Science | volume = 127 | issue = Pt 21 | pages = 4561–6 | date = November 2014 | pmid = 25205764 | pmc = 4215710 | doi = 10.1242/jcs.151068 }}

Finally, fingolimod has also been found to have other molecular targets and functions. Fingolimod has been reported to be a cannabinoid receptor antagonist,{{cite journal | vauthors = Paugh SW, Cassidy MP, He H, Milstien S, Sim-Selley LJ, Spiegel S, Selley DE | title = Sphingosine and its analog, the immunosuppressant 2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol, interact with the CB1 cannabinoid receptor | journal = Molecular Pharmacology | volume = 70 | issue = 1 | pages = 41–50 | date = July 2006 | pmid = 16571654 | doi = 10.1124/mol.105.020552 | s2cid = 11131541 }} a cPLA2 inhibitor{{cite journal | vauthors = Payne SG, Oskeritzian CA, Griffiths R, Subramanian P, Barbour SE, Chalfant CE, Milstien S, Spiegel S | title = The immunosuppressant drug FTY720 inhibits cytosolic phospholipase A2 independently of sphingosine-1-phosphate receptors | journal = Blood | volume = 109 | issue = 3 | pages = 1077–85 | date = February 2007 | pmid = 17008548 | pmc = 1785128 | doi = 10.1182/blood-2006-03-011437 }} and a ceramide synthase inhibitor.{{cite journal | vauthors = Berdyshev EV, Gorshkova I, Skobeleva A, Bittman R, Lu X, Dudek SM, Mirzapoiazova T, Garcia JG, Natarajan V | title = FTY720 inhibits ceramide synthases and up-regulates dihydrosphingosine 1-phosphate formation in human lung endothelial cells | journal = The Journal of Biological Chemistry | volume = 284 | issue = 9 | pages = 5467–77 | date = February 2009 | pmid = 19119142 | pmc = 2645812 | doi = 10.1074/jbc.M805186200 | doi-access = free }}{{cite journal | vauthors = Lahiri S, Park H, Laviad EL, Lu X, Bittman R, Futerman AH | title = Ceramide synthesis is modulated by the sphingosine analog FTY720 via a mixture of uncompetitive and noncompetitive inhibition in an Acyl-CoA chain length-dependent manner | journal = The Journal of Biological Chemistry | volume = 284 | issue = 24 | pages = 16090–8 | date = June 2009 | pmid = 19357080 | pmc = 2713526 | doi = 10.1074/jbc.M807438200 | doi-access = free }} It has also been reported to stimulate the repair process of glial cells and glial precursor cells after injury.{{cite journal | vauthors = Horga A, Montalban X | title = FTY720 (fingolimod) for relapsing multiple sclerosis | journal = Expert Review of Neurotherapeutics | volume = 8 | issue = 5 | pages = 699–714 | date = May 2008 | pmid = 18457527 | doi = 10.1586/14737175.8.5.699 | s2cid = 28071687 }}

History

First synthesized in 1992 by Yoshitomi Pharmaceuticals, fingolimod was derived from an immunosuppressive natural product, myriocin (ISP-I) through chemical modification. Myriocin was isolated from the culture broth a type of entomopathogenic fungus (Isaria sinclairii) that was an eternal youth nostrum in traditional Chinese medicine.{{cite journal | vauthors = Adachi K, Chiba K | title = FTY720 story. Its discovery and the following accelerated development of sphingosine 1-phosphate receptor agonists as immunomodulators based on reverse pharmacology | journal = Perspectives in Medicinal Chemistry | volume = 1 | pages = 11–23 | date = September 2007 | pmid = 19812733 | pmc = 2754916 | doi = 10.1177/1177391X0700100002 }} Showing positive results in both in vitro (mixed lymphocyte reaction) and in vivo screening (prolonging rat skin graft survival time), myriocin was modified through a series of steps to yield fingolimod, code named at the time FTY720.{{cite journal| doi = 10.1016/0960-894X(95)00126-E | vauthors = Fujita T, Yoneta M, Hirose R, Sasaki S, Inoue K, Kiuchi M, Hirase S, Adachi K, Arita M, Chiba K | title = Simple compounds, 2-alkyl-2-amino-1,3-propanediols have potent immunosuppressive activity | journal = Bioorg. Med. Chem. Lett. | volume= 5 | pages = 847–52 | year = 1995| issue = 8}} A recent review highlights the synthetic methods, mode of action and potential applications of this molecule.{{cite journal | vauthors = Balasubramaniam S, Sankaran GS, Badle SS |title=Perspective on FTY720, an Immunosuppressant |journal=Synthesis |volume=50 |issue=5 |pages=968–83 |doi=10.1055/s-0036-1591877 |year=2018 |s2cid=102682294 }}

Structure activity relationship (SAR) studies on myriocin homologs and partially synthetic derivatives showed that the configuration at the carbon bearing the 3-hydroxy group or the 14-ketone, the 6-double bond, and the 4-hydroxy group were not important for its activity and simplification of the structure of ISP-I was done in an attempt to reduce toxicity and improve drug ability.

Elimination of side chain functionalities and removal of chiral centers was part of the simplification process and an intermediate compound (ISP-I-28) with the carboxylic acid of myriocin transformed to a hydroxymethyl group was generated. ISP-I-28 was found to be less toxic and more effective at lengthening rat skin allograft time than ISP-1.

In September 2010, fingolimod became the first oral disease-modifying drug approved by the U.S. Food and Drug Administration (FDA) to reduce relapses and delay disability progression in patients with relapsing forms of multiple sclerosis.{{cite web | title=FDA approves first oral drug to reduce MS relapses | website=U.S. Food and Drug Administration (FDA) | date=22 September 2010 | url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm226755.htm | archive-url=https://web.archive.org/web/20170214051915/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm226755.htm | archive-date=14 February 2017 | url-status=dead | access-date=5 December 2019}} {{PD-notice}}{{cite web | title=Drug Approval Package: Brand Name (Generic Name) NDA # | website=U.S. Food and Drug Administration (FDA) | date=5 December 2019 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022527Orig1s000TOC.cfm | archive-url=https://web.archive.org/web/20191205234449/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022527Orig1s000TOC.cfm | archive-date=5 December 2019 | url-status=live | access-date=5 December 2019}} {{PD-notice}} In April 2011 Novartis said that the drug would be available in Canadian pharmacies.First oral MS treatment approved for Canada https://vancouversun.com/health/First+oral+treatment+approved+Canada+says+drug+company/4420028/story.html {{Webarchive|url=https://web.archive.org/web/20110427213431/http://www.vancouversun.com/health/First+oral+treatment+approved+Canada+says+drug+company/4420028/story.html |date=27 April 2011 }}{{cite news |url=http://www.news-medical.net/news/20110310/Novartis-new-MS-treatment-receives-Notice-of-Compliance-in-Canada.aspx |date=10 March 2011 |title=Novartis new MS treatment receives Notice of Compliance in Canada |publisher=NewsMedical.net }} In March 2011, the European Medicines Agency approved the drug for use in the European Union.{{cite web |url=http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F002202%2Fhuman_med_001433.jsp&murl=menus%2Fmedicines%2Fmedicines.jsp&mid=WC0b01ac058001d125 |title=EMA approval information about Gilenya |access-date=5 February 2022 |archive-date=14 April 2018 |archive-url=https://web.archive.org/web/20180414091554/http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F002202%2Fhuman_med_001433.jsp&murl=menus%2Fmedicines%2Fmedicines.jsp&mid=WC0b01ac058001d125 |url-status=dead }}

In 2016, a systematic review concluded that treatment of people relapsing-remitting multiple sclerosis is effective in reducing the probability of acute inflammatory relapses, with potentially little or no effect on disability progression, compared to placebo.{{cite journal | vauthors = La Mantia L, Tramacere I, Firwana B, Pacchetti I, Palumbo R, Filippini G | title = Fingolimod for relapsing-remitting multiple sclerosis | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | pages = CD009371 | date = April 2016 | issue = 4 | pmid = 27091121 | doi = 10.1002/14651858.CD009371.pub2 | pmc = 10401910 }} The risk/benefit profile compared to other disease-modifiying therapies being unclear due to a lack of direct comparisons.

In December 2019, generic fingolimod was approved in the United States for the treatment of relapsing forms of multiple sclerosis in adults.{{cite press release | title=FDA approves first generics of Gilenya | website=U.S. Food and Drug Administration (FDA) | date=5 December 2019 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-generics-gilenya | archive-url=https://web.archive.org/web/20191205230407/https://www.fda.gov/news-events/press-announcements/fda-approves-first-generics-gilenya | archive-date=5 December 2019 | url-status=live | access-date=5 December 2019}} {{PD-notice}} The FDA granted approvals of generic fingolimod applications to HEC Pharm Co. Limited, Biocon Limited and Sun Pharmaceutical Industries Limited.

On 19 July 2019, fingolimod received fast approval for use in China.{{cite press release |title=Novartis key multiple sclerosis product Gilenya approved in China |url=https://www.novartis.com/news/media-releases/novartis-key-multiple-sclerosis-product-gilenya-approved-china |website=Novartis }}

Society and culture

= Legal status =

In 2015, after a challenge at the US Patent and Trademark Office by a generic competitor, the patent office quashed Novartis's patent claims stating they were obvious. Novartis appealed and the federal circuit upheld the patent office decision in April 2017, leaving a high likelihood of generics coming to market by 2019.{{cite news| vauthors = Sagonowsky E |title=Novartis' Gilenya patent loss sets MS market up for battle with early generics|url=https://www.fiercepharma.com/pharma/novartis-loses-gilenya-patent-appeal-knocking-off-years-protection|work=FiercePharma|date=13 April 2017}}

In January 2020, a panel of judges at the Court of Appeal for the Federal Circuit called into question the validity of the last remaining orange book patent protecting Gilenya.{{cite web|url=http://oralarguments.cafc.uscourts.gov/default.aspx?fl=2018-2209.mp3|title=CAFC Oral Argument Recording}}

In October 2022, the Supreme Court turned down a request by Novartis to block the launch of generic versions of Gilenya in the United States.{{cite web |title=Search - Supreme Court of the United States |url=https://www.supremecourt.gov/search.aspx?filename=/docket/docketfiles/html/public/22a272.html |access-date=17 October 2022 |website=U.S. Supreme Court}}{{cite news | vauthors = Kansteiner F |date=14 October 2022 |title=Novartis' blockbuster Gilenya exposed to generics in short term amid Supreme Court appeal |url=https://www.fiercepharma.com/pharma/novartis-28b-ms-med-gilenya-exposed-generics-short-term-larger-supreme-court-decision-looms |access-date=17 October 2022 |website=Fierce Pharma }}

In April 2023, the U.S. Supreme Court declined to hear Novartis's request to revive a key patent on Gilenya that had been invalidated by a lower court.{{cite news | vauthors = Brittain B |date=2023-04-17 |title=US Supreme Court rebuffs Novartis bid to revive MS drug Gilenya patent |language=en |work=Reuters |url=https://www.reuters.com/legal/us-supreme-court-rebuffs-novartis-bid-revive-ms-drug-gilenya-patent-2023-04-17/ |access-date=2023-04-18}}

Research

Clinical trials are ongoing to prevent neuropathic pain in patients with breast cancer treated with paclitaxel.{{cite web|url= https://neurosciencenews.com/chemo-brain-drug-21353/|title=Unlocking the Mystery of "Chemo Brain"|date=2 September 2022}} Recently, the fingolimod molecule has been incorporated in mRNA delivery vehicles to increase targeting of lymphocytes expressing the S1P1 receptor in pre-clinical models.{{cite journal | vauthors = Testa S, Haabeth OA, Blake TR, Del Castillo TJ, Czerwinski DK, Rajapaksa R, Wender PA, Waymouth RM, Levy R | title = Fingolimod-Conjugated Charge-Altering Releasable Transporters Efficiently and Specifically Deliver mRNA to Lymphocytes In Vivo and In Vitro | journal = Biomacromolecules | volume = 23 | issue = 7 | pages = 2976–2988 | date = July 2022 | pmid = 35748182 | doi = 10.1021/acs.biomac.2c00469 | pmc = 10199726 | s2cid = 249989444 }}

References

{{Reflist}}

{{Demyelinating diseases of CNS}}

{{Immunosuppressants}}

{{Lysophospholipid signaling}}

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Category:Diols

Category:Immunosuppressants

Category:Drugs developed by Novartis

Category:Multiple sclerosis

Category:S1P receptor modulators