Zeposia (ozanimod) for multiple sclerosis
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What is Zeposia for MS?
Zeposia (ozanimod) is an approved oral treatment that helps to reduce relapse rates and the development of new brain lesions in people with multiple sclerosis (MS). The therapy was developed by Celgene, a Bristol Myers Squibb company.
Therapy Snapshot
| Brand Name: | Zeposia |
| Chemical Name: | Ozanimod |
| Usage: | Disease-modifying therapy for relapsing forms of MS |
| Administration: | Oral capsules |
How does Zeposia work?
In MS, the body’s immune system accidentally launches an inflammatory response that targets the myelin sheath, a fatty coating around nerve fibers that is essential for ensuring normal nervous system function.
Zeposia belongs to a class of treatments called sphingosine 1-phosphate (S1P) receptor modulators. By binding to S1P protein receptors on immune cells, these medications work to “trap” inflammatory cells inside lymph nodes — the immune organs where those cells are matured and stored. This prevents inflammatory cells from getting into the brain and spinal cord, where they could cause damage.
S1P receptors also are found on some cells in the brain and spinal cord, such as nerve cells and oligodendrocytes, the cells that make myelin. Zeposia is able to cross the selective blood-brain barrier that protects the brain from harmful substances in the blood, and may promote the survival and growth of these cells, potentially supporting nervous system health.
Who with MS can take Zeposia?
The U.S. Food and Drug Administration approved Zeposia in 2020 for the treatment of adults with relapsing forms of MS. These include relapsing-remitting MS (RRMS), active secondary progressive MS (SPMS), and clinically isolated syndrome.
That same year, the medication was approved in the European Union and Canada, but only for adults with RRMS and active disease.
Who should not take Zeposia?
Zeposia is not recommended for people who:
- experienced a heart attack, chest pain (unstable angina), stroke or mini-stroke, or certain types of heart failure in the last six months
- have or have had abnormal heart rhythms (arrhythmia) that are not corrected with a pacemaker
- have severe, untreated sleep apnea, a sleeping disorder
- are receiving treatment with a class of antidepressants called monoamine oxidase inhibitors
Zeposia is not approved for children and adolescents younger than 18. The medication’s safety and efficacy in these populations have not been established.
How is Zeposia administered?
Zeposia is available in hard capsules that come in three strengths:
- 0.23 mg capsules, with a light gray cap printed with “OZA” in black ink, and a light gray body printed with “0.23 mg”
- 0.46 mg capsules, with an orange cap printed with “OZA,” and a light gray body printed with “0.46 mg”
- 0.92 mg capsules, with an orange cap and body, printed with “OZA” and “0.92 mg”
The recommended dose of Zeposia is 0.92 mg, taken orally once a day. Patients starting on the medication will first take the 0.23 mg dose over days 1–4 and increase to the 0.46 mg dose for days 5–7. Dosing with the recommended 0.92 mg capsule begins on day eight.
A similar dosage increase is needed if patients miss a dose within the first two weeks of treatment.
The capsules should be swallowed whole. Zeposia may be taken with or without food, although certain foods containing large amounts of the natural compound tyramine — such as aged, fermented, cured, smoked, and pickled foods — are not recommended during treatment.
| Administration | Oral capsules |
| Dosage | 0.23 mg, 0.46 mg, 0.92 mg |
| Timing | 0.23 mg dose over days 1–4, 0.46 mg dose for days 5–7; dosing with the recommended 0.92 mg capsule begins on day eight |
Zeposia in clinical trials
RADIANCE Part A
Zeposia showed promising results in two Phase 1 trials involving healthy volunteers. Following those studies, Celgene launched a Phase 2/3 clinical trial, called RADIANCE, to evaluate Zeposia in people with relapsing MS and active disease, as defined by the presence of relapses and/or inflammatory brain lesions.
The trial’s Phase 2 part (NCT01628393) enrolled 258 patients across the U.S. and Europe. Participants were randomly assigned to receive Zeposia (0.5 mg or 1.0 mg) or a placebo, once daily for 24 weeks. In RADIANCE Part A, both doses significantly reduced the total number of inflammatory lesions and the cumulative number of new or enlarging lesions by more than 80%, compared with the placebo. However, both doses failed to lower relapse rates relative to the placebo.
Most patients in this part then entered an open-label extension, in which all were treated with Zeposia for about two more years. Results from the trial and its extension showed that the number of inflammatory lesions, new lesions, and relapse rates remained low in patients originally assigned to Zeposia, and decreased in the placebo group after those individuals switched to the medication.
RADIANCE Part B and SUNBEAM trials
Findings from the second, Phase 3 portion of the RADIANCE study (NCT02047734), and from another Phase 3 clinical trial called SUNBEAM (NCT02294058) then supported the regulatory approvals of Zeposia.
Collectively, these two trials enrolled more than 2,600 participants with RRMS or active SPMS. All were randomly assigned to receive one of two doses of the therapy — 0.92 mg or 0.46 mg, once daily — or Avonex (interferon beta-1a), given weekly. Avonex is an approved MS therapy that is given via intramuscular injection, or injected directly into the muscle tissue.
In RADIANCE Part B, all patients were treated for up to two years. The results from this trial demonstrated that the 0.92 mg dose of Zeposia significantly lowered annualized relapse rates, by 38%, and reduced the number of new brain lesions, by 42%, compared with Avonex.
Similar findings were observed in SUNBEAM, in which participants received treatment for at least one year. In this trial, the 0.92 mg dose of Zeposia significantly lowered the number of relapses per year and the number of new or enlarging brain lesions (both by 48%), compared with Avonex.
Brain lesions with active inflammation also were reduced by more than 50% in both trials. A pooled analysis of the two trials, however, showed no significant differences in the proportion of participants with confirmed disability worsening across both treatments.
Ongoing trial
An ongoing Phase 3 open-label extension study is seeking to determine Zeposia’s long-term safety and efficacy.
Called DAYBREAK (NCT02576717), the trial is evaluating the therapy in patients who participated in earlier trials — 2,495 people worldwide. Participants are receiving Zeposia daily for up to seven years.
Common side effects of Zeposia
The most common side effects of Zeposia in MS patients are:
- high blood pressure
- an unusual drop in blood pressure upon standing, called orthostatic hypotension
- back pain
- elevated levels of liver enzymes
- upper respiratory infections
- urinary tract infections
Heart and lung problems
Zeposia can cause a temporary decrease in heart rate and an increase in blood pressure. Heart health should be checked thoroughly prior to starting treatment, and blood pressure should be monitored while taking the medication.
The medication also can decrease lung function — causing patients to have shortness of breath — which should be checked if appropriate.
Liver injury
Zeposia may induce liver damage. Liver function should be assessed before starting treatment, and the medication should be stopped if significant liver injury occurs.
Infections and vaccines
Because this medication prevents immune cells from entering the blood, it may increase the risk of infections, such as serious cases of shingles (herpes zoster). Immune cells counts should be checked before starting treatment and patients should be continuously monitored for infections.
For at least three months after stopping the therapy, patients on Zeposia should not receive vaccines that contain a live virus. Zeposia may decrease the effectiveness of these vaccines. In patients who have not had chickenpox or a vaccine for chickenpox, a full course of vaccination against the varicella zoster virus is recommended before starting Zeposia.
PML
Zeposia can increase the risk of a rare viral infection called progressive multifocal leukoencephalopathy, or PML. This viral infection of the brain usually results in death or severe disability. The medication should be stopped immediately if a patient shows signs of PML.
Eye problems
Macular edema, a form of swelling in the eye, may occur during Zeposia treatment. Patients with diabetes or a form of eye inflammation called uveitis are especially at risk. Anyone experiencing any change in vision while taking Zeposia should undergo prompt ophthalmic evaluation. Those at higher risk should undergo an evaluation before starting the therapy.
Pregnancy and breastfeeding
Animal studies suggest that Zeposia can cause harm to a developing fetus. It is recommended that patients who are able to become pregnant use effective contraception while taking Zeposia, and for three months after stopping treatment.
Patients who plan to breastfeed should inform their healthcare providers, as research in animal models has found traces of Zeposia in breast milk.
Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about Zeposia
Zeposia was approved by the U.S. Food and Drug Administration in March 2020 for the treatment of adults with relapsing forms of multiple sclerosis (MS). Indications for use include relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome. Zeposia also is approved in the U.S. for ulcerative colitis, an inflammatory bowel disease.
Zeposia is not recommended for pregnant patients as it may cause harm to a developing fetus. Patients who plan or are able to become pregnant should use contraception methods while on Zeposia and for three months after stopping treatment.
There are no known interactions between Zeposia and alcohol. However, because alcohol may interfere with some disease symptoms and medications, patients are advised to discuss safe alcohol consumption with their healthcare provider.
Results may be seen in as little as three months. In the RADIANCE Part A trial, which compared Zeposia against a placebo in patients with relapsing forms of multiple sclerosis (MS), a significant increase in the number of patients without inflammatory brain lesions was evident with Zeposia treatment as soon as 12 weeks after the therapy’s start. However, because MS affects each person differently, patients should discuss with their healthcare teams how the medication can help in their specific case.
Neither hair loss nor weight gain was reported in clinical trials as side effects of Zeposia. Patients who experience such effects after starting on the medication should discuss these issues with their healthcare providers.
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