Fingolimod is an immunomodulating drug, mostly used for treating multiple sclerosis (MS). It has reduced the rate of relapses in relapsing-remitting multiple sclerosis by approximately one-half over a two-year period. Fingolimod is a sphingosine-1-phosphate receptor modulator, which sequesters lymphocytes in lymph nodes, preventing them from contributing to an autoimmune reaction.
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. 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.
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 drugability.
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 Food and Drug Administration to reduce relapses and delay disability progression in patients with relapsing forms of multiple sclerosis.
In March 2011, the European Medicines Agency approved the drug for use in the European Union
In April 2011 Novartis said that the drug would be available in Canadian pharmacies.
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.
Novartis announced that the US Food and Drug Administration (FDA) has approved Gilenya (fingolimod) for the treatment of children and adolescents 10 to less than 18 years of age with relapsing forms of multiple sclerosis (RMS), making it the first disease-modifying therapy indicated for these patients.