Ozanimod (Zeposia) became the third oral S1P modulator approved by the FDA for the treatment of multiple sclerosis,
Multiple sclerosis (MS) is an autoimmune condition that is one of the leading causes of non-traumatic neurological disabilities in young adults, characterized by damage to the brain and spinal cord.
This autoimmune condition disease causes the immune system to attack the myelin sheath of the central nervous system (CNS), resulting in inflammation, scarring, and lesions to the protective layer around nerve fibers.
Symptoms of MS include numbness, tingling, mood changes, memory issues, pain, fatigue, blindness, and paralysis. These unpredictable symptoms can be temporary or even long-lasting. MS can be categorized into 3 types: primary progressive MS (PPMS), secondary progressive MS (SPMS), and relapsing-remitting MS (RRMS).1
On March 26, 2020, Bristol Myers Squibb (BMS) announced the FDA approval of ozanimod (Zeposia), becoming the third oral S1P modulator for MS. The drug’s approval was based on 2 trials resulting in greater reductions in annualized relapse rates compared another MS medication. However, after receiving approval from the FDA, BMS has decided to postpone its launch because of the coronavirus disease 2019 pandemic.
In the meantime, taking advantage of its immunomodulating mechanism, BMS is looking to expand Zeposia’s use into other inflammatory diseases, such as ulcerative colitis. The company announced “highly statistically significant” benefits in moderate-to-severe ulcerative colitis, hitting both primary endpoints and several key secondary targets.2
The safety and efficacy of ozanimod in the treatment of MS were demonstrated in the phase 3 SUNBEAM and RADIANCE Part B trials. Both trials were double-blind, double-dummy, parallel-group, active comparator-controlled clinical trials.
The primary endpoint for both trials were annualized relapse rates (ARR). The secondary MRI endpoints were new or enlarging brain lesions. Both trials included patients who had experienced at least 1 relapse within the prior year or prior 2 years with evidence of lesions. Patients with primary progressive MS were excluded.
SUNBEAM evaluated 1346 patients randomized to receive 0.92 mg oral ozanimod and intramuscular injections of 30 mcg Avonex (interferon beta-1a) during a 12-month treatment period. RADIANCE Part B evaluated 1320 patients during a 24-month treatment period.1 The ARR were significantly lower in patients treated with ozanimod 0.92 mg than in patients who were receiving Avonex 30 mcg. Furthermore, the number of new or enlarged lesions were significantly lower.
In addition to these trials, in an active-controlled MS clinical trial, the mean lymphocyte count decreased to approximately 45% of baseline at 3 months and low lymphocyte counts were maintained while patients were on treatment with ozanimod. After discontinuing the maintenance dosage of 0.92 mg, the median time for blood lymphocytes to return to normal range was 30 days.3
Before initiation of treatment with ozanimod, it is necessary to assess complete blood count, cardiac evaluation (ECG), liver function tests (LFT), ophthalmic assessment, current medications and vaccinations.
Oral capsule strengths: 0.23mg, 0.46mg, 0.92mg
Adult: Zeposia is initiated on an oral dosing titration regimen:
Contraindications/Warnings and Precautions
Ozanimod is contraindicated in patients with recent (within last 6 months) myocardial infarctions, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, Class III/IV heart failure, second or third degree AV block, sick sinus syndrome, or SA block.
There is an increased risk of infections while taking ozanimod and monitoring is required during and for up to 3 months following treatment.
Monitor for BP changes, hepatic dysfunction, respiratory function, and vision changes during treatment. Advise female patients of reproducing age to use effective contraception during and for up to 3 months after discontinuation.
Vaccines: Avoid the use of live attenuated vaccines during and following 3 months of treatment with ozanimod.
Strong CYP2C8 inhibitors: Co-administration is not recommended (eg, Gemfibrozil).
BCRP inhibitors: Co-administration is not recommended (eg, Cyclosporine).
Strong CYP2C8 inducers: Co-administration should be avoided (eg, Rifampin).
Avoid concomitant use of drugs or OTC medications that increase norepinephrine or serotonin such as opioids, SSRI, SNRI, TCA, and tyramine. Avoid high amounts (>150 mg) of tyramine-containing foods (eg, age cheese, pickled herring).
The most common adverse reactions (> 4%) in patients included upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension.4
Use in Special Populations
Pregnancy: There is no adequate data on the risk of ozanimod in pregnant women. In animal studies, there were adverse effects on the development including embryolethality, fetal malformations, and neurobehavioral changes. The receptor affected (sphingosine-1-phosphate) has been demonstrated to have an important role in embryogenesis, including vascular and neural development.
Lactation: There are no data of ozanimod in human milk, the effects on the breastfed infant, or effects of the drug on milk production.
Pediatric use: Safety and effectiveness in pediatric patients has not been established.
Geriatric use: Studies of Zeposia did not sufficiently determine whether the medication responded differently in geriatric patients compared with younger subjects. It is recommended to use caution in elderly patients due to greater frequencies of decreased hepatic, renal, or cardiac function.
Storage and Handling
Zeposia should be stored at room temperature (68F to 77F). Keep medicine out of reach from children.5
About the Authors
Rahman Gul is a PharmD candidate at Shenandoah University’s Bernard J. Dunn School of Pharmacy, anticipated to graduate in Spring 2021.Jonathan Ogurchak, PharmD, CSP, is the founder and CEO of STACK, a pharmacy compliance management software, and serves as preceptor for a virtual Advanced Pharmacy Practice Experiential Rotation for specialty pharmacy, during which this article was composed.