|Elimination half-life||19 hours|
|Chemical and physical data|
|Molar mass||404.470 g·mol−1|
|3D model (JSmol)|
Ozanimod, sold under the brand name Zeposia, is an immunomodulatory drug for the treatment of relapsing multiple sclerosis (RMS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. It acts as a sphingosine-1-phosphate (S1P) receptor agonist, sequestering lymphocytes to peripheral lymphoid organs and away from their sites of chronic inflammation. Ozanimod was discovered by The Scripps Research Institute in San Diego, by the labs of Hugh Rosen and Edward Roberts, and licensed to the biotech company Receptos Inc.  Receptos was acquired by Celgene for $7.2 billion.
The most common adverse reactions are upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension.
Ozanimod is an agonist of the S1P1 and S1P5 receptors. It demonstrates this effect in a dose-dependent manner, with 10-fold potency to three comparators. This is an improvement of selectivity over its predecessor, fingolimod, which is non-specific to all 5 isotypes. The agonism of S1P directly causes its internalization and degradation through the ubiquitin-proteosome pathway. The loss of S1P leads to a decrease in the total lymphocyte count in circulation, specifically CD4+ CCR7+ and CD8+ CCR7+ T cells.
Ozanimod has a high oral bioavailability, a circulating half-life of about 19 hours, and reaches highest blood plasma concentrations after about 6 hours. Ozanimod is dehydrogenated by two CYP enzymes into two active metabolites, all with similar pharmacokinetics. The decrease in lymphocyte count lasts for approximately 14 days after treatment discontinuation. Unlike fingolimod, it does not require phosphorylation for activation, nor does it demonstrate cardiac abnormalities or hepatotoxicity.
Touchstone is a double-blind, placebo controlled phase II clinical for the treatment of ulcerative colitis.Clinical trial number NCT01647516 at ClinicalTrials.gov. 197 patients, ages 18–75, with moderate to severe UC (Mayo Score 6-10) were recruited and assigned either placebo, 0.5 mg or 1 mg of oral ozanimod followed by 1 week of dose escalation. The 1 mg dose showed a slight increase in rate of clinical remission of UC and total lymphocyte decrease as compared to the placebo, with the most common adverse effects being headaches and anemia. The authors noted that limitations on this study included a brief duration and small sample size, meaning they could not assess safety nor efficacy.
Radiance is a double-blind, placebo controlled phase combined II/III clinical trial for the treatment of relapsing multiple sclerosis. For the phase II trial, 258 patients, ages 18–55 with RMS (Mean Expanded Disability Status Scale of 2.9) were assigned either placebo, 0.5 mg or 1 mg of oral ozanimod followed by 1 week of dose escalation. Ozanimod significantly reduced MRI lesion activity in participants with relapsing multiple sclerosis over a period of 24 weeks. Both doses of ozanimod reached anticipated range of 60-70% decreased lymphocyte count, and were well tolerated, with a safety profile consistent with a previous phase 1 study in healthy volunteers. The most common adverse effects as compared to the placebo were: nasopharyngitis, headache, and urinary-tract infections, with no serious infectious or cardiac adverse effects. With these results, both doses of ozanimod were taken forward into the 2-year long phase III trial and is completed but unpublished as of November 2016.
Sunbeam is the second RMS phase III clinical trial to establish the dose with optimum safety-benefit relationship, with an estimated size of 1200 patients. It began in November 2014 and has an estimated completion date of February 2017.
After going public in May 2013, Receptos, Inc. stock surged with the clinical data ozanimod displayed as a S1P immunomodulating drug. In August 2015, Receptos was acquired by Celgene for $7.2 billion through a combination of cash in hand and new debt, leading to a 22% increase in their stock value. Receptos, Inc. (Celgene) patented the synthesis of ozanimod in July 2016. With the expansion of Celgene's inflammation and immunology profile, the company had been expecting to generate $4 to $6 billion in annual sales from ozanimod; however, the FDA rejected its application for the drug's approval in February 2018. Celgene refiled in March 2019. As the new owner, Bristol-Myers Squibb received FDA approval on March 26, 2020, for ozanimod (Zeposia) oral capsules to treat adults with relapsing forms of multiple sclerosis (MS), including relapsing-remitting MS (RRMS), active secondary progressive MS (SPMS), and clinically isolated syndrome (CIS). Ozanimod was approved for medical use in the European Union in May 2020, and in Australia in July 2020.
The US Food and Drug Administration (FDA) approved ozanimod based on evidence from two clinical trials (Trial 1/NCT 02294058 and Trial 2/ NCT02047734) of 1767 subjects with relapsing forms of multiple sclerosis. The trials were conducted at 173 centers in the United States, Belarus, Poland, Russia and Ukraine. Subjects received ozanimod or comparator (interferon β1a, a product approved for the treatment of relapsing forms of multiple sclerosis) for up to one year (in Trial 1) or up to two years (in Trial 2). Neither the subjects nor the health care providers knew which treatment was being given until the trials were completed. The benefit of ozanimod was evaluated based on the percentage of subjects who experienced reduction in disease relapse in comparison to subjects treated with interferon β1a.
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