Zeposia (ozanimod) - 2 indications

Scroll down for information on each indication:

• Relapsing forms of multiple sclerosis; approved March of 2020
• Moderately to severely active ulcerative colitis (UC) in adults; approved May of 2021

General Information

Zeposia (ozanimod) is a sphingosine 1-phosphate receptor modulator. 

Zeposia is specifically indicated for the following:

• the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults
• moderately to severely active ulcerative colitis (UC) in adults

Zeposia is supplied as a capsule for oral administration. Before initiation of treatment with Zeposia, assess the following:

• Complete Blood Count: Zeposia may increase the risk of infections. Obtain a complete blood count (CBC) before initiation of treatment. Monitor for infection during treatment and for 3 months after discontinuation. Do not start Zeposia in patients with active infections.
• Cardiac Evaluation: Zeposia may result in transient decrease in heart rate; titration is required for treatment initiation. Check an electrocardiogram (ECG) to assess for preexisting cardiac conduction abnormalities before starting  Zeposia.
• Liver Function Tests: Discontinue if significant liver injury is confirmed. Obtain liver function tests before initiating Zeposia.
• Ophthalmic Assessment: In patients with a history of uveitis or macular edema, obtain an evaluation of the fundus, including the macula .
• Current or Prior Medications: * If patients are taking anti-neoplastic, immunosuppressive, or immune-modulating therapies, or if there is a history of prior use of these drugs, consider possible unintended additive immunosuppressive effects before initiating treatment with Zeposia. * Determine if patients are taking drugs that could slow heart rate or atrioventricular conduction
• Vaccinations: Test patients for antibodies to varicella zoster virus (VZV) before initiating Zeposia; VZV vaccination of antibody-negative patients is recommended prior to commencing treatment.  If live attenuated vaccine immunizations are required, administer at least 1 month prior to initiation of Zeposia.

The recommended dose of Zeposia is as follows:

Treatment Initiation: Initiate Zeposia with a 7-day titration according to this schedule:

• Days 1-4: 0.23 mg once daily
• Days 5-7: 0.46 mg once daily
• Day 8 and thereafter: 0.92 m g once daily

Maintenance Dosage: After initial titration, the recommended maintenance dosage of Zeposia is 0.92 mg taken orally once daily starting on Day 8. 

Zeposia capsules should be swallowed whole and can be administered with or without food.

If a dose of Zeposia is missed during the first 2 weeks of treatment, reinitiate treatment using the titration regimen.

If a dose of Zeposia is missed after the first 2 weeks of treatment, continue with the treatment as planned.

Mechanism of Action

Ozanimod is a sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. Ozanimod blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood.  The mechanism by which ozanimod exerts therapeutic effects in multiple sclerosis is unknown but may involve the reduction of lymphocyte migration into the central nervous system.

Side Effects

Adverse effects associated with the use of Zeposia may include, but are not limited to, the following:

• upper respiratory infection
• hepatic transaminase elevation
• orthostatic hypotension
• \urinary tract infection
• back pain
• hypertension 

Indication 1 - Relapsing forms of multiple sclerosis

approved March of 2020

Clinical Trial Results

The FDA approval of Zeposia was based on the randomized, active-controlled Phase 3 SUNBEAM (safety and efficacy of Zeposia versus interferon beta-1a in relapsing multiple sclerosis) and RADIANCE (safety and efficacy of the selective sphingosine 1-phosphate receptor modulator Zeposia in relapsing multiple sclerosis) Part B clinical trials. Both head-to-head trials compared Zeposia to Avonex (interferon beta-1a).

SUNBEAM was a pivotal, multicenter, randomized, double-blind, double-dummy, active-controlled trial evaluating the efficacy, safety and tolerability of oral Zeposia (0.92 mg, equivalent to 1 mg) against weekly intramuscular Avonex (interferon beta-1a) for at least a 12-month treatment period. The study included 1,346 people with RMS across 152 sites in 20 countries. The primary endpoint of the trial was annualized relapse rates (ARR) during the treatment period.

RADIANCE Part B was a pivotal, multicenter, randomized, double-blind, double-dummy, active-controlled trial evaluating the efficacy, safety and tolerability of oral Zeposia (0.92 mg, equivalent to 1 mg) against weekly intramuscular Avonex (interferon beta-1a) over a 24-month treatment period. The study included 1,320 people with RMS across 150 sites in 21 countries. The primary endpoint of the trial was ARR over 24 months

• Zeposia demonstrated a relative reduction in ARR versus Avonex of 48% through one year and 38% at two years (absolute ARR of 0.18 versus 0.35 and 0.17 versus 0.28, respectively).
• At one year, treatment with Zeposia reduced the number of T1-weighted gadolinium-enhanced (GdE) brain lesions more than Avonex (0.16 vs 0.43), a relative reduction of 63%, and reduced the number of new or enlarging T2 lesions (1.47 vs. 2.84), a relative reduction of 48%.
• At two years, treatment with Zeposia reduced the number of T1-weighted gadolinium-enhanced (GdE) brain lesions more than Avonex (0.18 vs 0.37), a relative reduction of 53%. Zeposia also reduced the number of new or enlarging T2 lesions vs Avonex (1.84 vs 3.18), a relative reduction of 42%.

There was no statistically significant difference in the three-month and six-month confirmed disability progression between ZEPOSIA- and AVONEX- treated patients over two years.

Indication 2 - Moderately to severely active ulcerative colitis (UC) in adults

approved May of 2021

Clinical Trial Results

The approval is based on data from True North, a pivotal Phase 3 trial evaluating Zeposia as an induction and maintenance therapy versus placebo in adult patients with moderately to severely active UC. In the 10 week induction study (UC Study 1), a total of 645 patients were randomized 2:1 to receive Zeposia (N=429) or placebo (N=216), of whom 94% and 89%, respectively, completed the induction study. In maintenance (UC Study 2), a total of 457 patients who received Zeposia in either UC Study 1 or in an open-label arm and achieved clinical response at Week 10 were re-randomized 1:1 and were treated with either Zeposia 0.92 mg (N=230) or placebo (N=227) for 42 weeks, for a total of 52 weeks of treatment.

During induction at Week 10 (Zeposia N=429 versus placebo N=216) the trial met its primary endpoint of clinical remission (18% versus 6%) as well as key secondary endpoints, including clinical response (48% versus 26%), endoscopic improvement (27% versus 12%) and endoscopic-histologic mucosal improvement (13% versus 4%) for Zeposia versus placebo, respectively. During maintenance at Week 52 (Zeposia N=230 versus placebo N=227) the trial met its primary endpoint of clinical remission (37% versus 19%) as well as key secondary endpoints, including clinical response (60% versus 41%), endoscopic improvement (46% versus 26%), corticosteroid-free clinical remission (32% versus 17%) and endoscopic-histologic mucosal improvement (30% versus 14%) for Zeposia versus placebo, respectively. Decreases in rectal bleeding and stool frequency subscores were observed as early as Week 2 (i.e.,1 week after completing the required 7-day dosage titration) in patients treated with Zeposia.