Development of oral agent in the treatment of multiple sclerosis: how the first available oral therapy, fingolimod will change therapeutic paradigm approach.
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, traditionally considered to be an autoimmune, demyelinating disease. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. At present, there are five licensed first-line disease-modifying drugs and two second-line treatments in MS. Currently available MS therapies have shown significant efficacy throughout many trials, but they produce different side-effect profiles in patients. Since they are well known and safe, they require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Thus, there is an important need for the development of new therapeutic strategies. Several oral compounds are in late-stage development for treating MS. Fingolimod (FTY720; Novartis, Basel, Switzerland) is an oral sphingosine-1-phosphase receptor modulator which has demonstrated superior efficacy compared with placebo and interferon β-1a in Phase III studies and has been approved in the treatment of MS. We summarily review the oral compounds in study, focusing on the recent development, approval and the clinical experience with FTY720.
Department of Neurosciences, S Camillo Forlanini Hospital, University of Rome Sapienza, Rome, Italy. c.gasperini@libero.it
Claudio
C
Gasperini
Serena
S
Ruggieri
D000284:Administration, Oral; D000818:Animals; D015195:Drug Design; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000503:physiopathology; D011409:Propylene Glycols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D049349:Receptors, Lysosphingolipid / Q000187:drug effects / Q000378:metabolism; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D016899:Interferon-beta; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine; D000068556:Interferon beta-1a