FDA Approves Zeposia^® (ozanimod) for the Treatment of Relapsing Forms of MS

Reviewed by MSAA Chief Medical Officer Barry A. Hendin, MD

Overview

On March 26, 2020, Bristol Myers Squibb announced that the United States Food and Drug Administration (FDA) approved Zeposia^® (ozanimod) for the treatment of adults with relapsing forms of multiple sclerosis (RMS), including clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active secondary-progressive MS (SPMS). Zeposia is an oral medication given once daily as a 0.92 mg pill.

Patients taking Zeposia for the first time start with a titration, which means that it is begun at a lower dose and gradually increased until the full dose is reached. With this newly approved medication, starting at a lower dose reduces the risk of a transient decrease in heart rate and atrioventricular conduction delays, which may occur if a larger dose is introduced too quickly.

Zeposia is a sphingosine-1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. It joins two other previously approved S1P receptor modulators: Gilenya^® (fingolimod) and Mayzent^® (siponimod); additional S1P receptor modulators are also under investigation. Ponesimod is among those still under investigation and it was recently submitted to the FDA for approval. According to the manufacturer, Zeposia is the only approved S1P receptor modulator that offers RMS patients an initiation that does not require a genetic test or label-based first-dose observation.

S1P receptor modulators are thought to work by blocking potentially damaging immune-system cells (lymphocytes) from leaving lymph nodes, lowering their number in the blood and tissues. These treatments may reduce damage to the central nervous system (CNS). In clinical trials of more than 2,600 adults with relapsing forms of MS, Zeposia was shown to have a significant effect on reducing the annual relapse rate (ARR) as well as the number of brain lesions, when compared to Avonex^® (interferon beta-1a).

Bristol Myers Squibb is delaying the launch of Zeposia and released the following statement, “As the country’s healthcare system is dealing with the unprecedented COVID-19 pandemic, Bristol Myers Squibb has made the decision to delay commercialization of Zeposia. The Company made the decision based on what’s in the best health interest of our patients, customers and employees. Bristol Myers Squibb will continue to monitor the environment and will partner with the neurology community to inform launch timing.” MSAA will inform the MS community of a launch date once it is announced.

Clinical Trial Results

In its announcement, Bristol Myers Squibb explains that the FDA’s approval is based on data from the largest pivotal, head-to-head RMS studies with an active comparator (Avonex) to date. These two pivotal studies include the Phase III SUNBEAM™ (safety and efficacy of Zeposia versus interferon beta-1a in relapsing multiple sclerosis) clinical trial, and the Phase III RADIANCE™ (safety and efficacy of the selective sphingosine 1-phosphate receptor modulator Zeposia in relapsing multiple sclerosis) Part B clinical trial.

Both trials compared daily doses of Zeposia to weekly intramuscular injections of Avonex. The SUNBEAM trial included 1,346 people living with RMS across 152 sites in 20 countries; the RADIANCE trial (Part B) included 1,320 people living with RMS across 150 sites in 21 countries.

Combined data from both studies are as follows:

• Compared to Avonex, Zeposia demonstrated a relative reduction of the annual relapse rate (ARR) by 48% through the first year and by 38% at two years.
• Compared to Avonex at one year, Zeposia demonstrated a relative reduction of T1-weighted gadolinium-enhanced (GdE) brain lesions by 63%, and demonstrated a relative reduction of new or enlarging T2 lesions by 48%.
• Compared to Avonex at two years, Zeposia demonstrated a relative reduction of T1-weighted gadolinium-enhanced (GdE) brain lesions by 53%, and demonstrated a relative reduction of new or enlarging T2 lesions by 42%.
• No statistically significant difference was found in the three-month and six-month confirmed disability progression between the two treatment groups during the course of two years.
• From a presentation given at the 2018 ECTRIMS conference (prior to the approval of Zeposia), MSAA’s 2019 MS Research Update reported that Zeposia was also shown in the SUNBEAM trial to prevent or delay cognitive deficits. MS can slow “processing speed” (the time needed to perform a mental task). In an analysis of more than 1,300 people who received either Zeposia or Avonex, clinically meaningful improvement in processing speed was shown in those receiving Zeposia, as measured by the Symbol Digit Modalities Test (SDMT).

Safety, Contraindications, and Adverse Events

According to the makers of Zeposia, this medication has shown acceptable levels of safety and tolerability in the Phase III trials. It should not be taken by patients who have experienced certain heart problems or stroke in the last six months, who have severe untreated sleep apnea, or who are taking a monoamine oxidase inhibitor.

Prior to starting Zeposia, patients need to be evaluated through a complete blood count, an electrocardiogram to determine any preexisting heart-rhythm abnormalities, a recent liver function test, and a history of medications and vaccinations. Anyone who has experienced macular edema (swelling behind the eye) or uveitis (inflammation in the middle layer of tissue in the eye wall) will also need to be evaluated.

The most common adverse reactions occurring in 4% or more of the study participants include: upper respiratory infection; elevated liver enzymes, which could indicate inflammation; orthostatic hypotension, which is a sudden drop in blood pressure when changing position, such as when standing up from a sitting position; urinary tract infection; back pain; and high blood pressure. Warnings and precautions include an increased risk of infections, heart-rhythm issues, liver injury, fetal risk if pregnant while taking Zeposia, a decline in pulmonary (respiratory) function, and macular edema (swelling behind the eye). Additional warnings and limitations are specified in the prescribing information.

A Message from MSAA’s Chief Medical Officer

MSAA Chief Medical Officer Barry A. Hendin, MD is pleased to see another option soon to be available to the MS community. He states, “We welcome another therapeutic option for treating relapsing forms of MS. The approval of Zeposia brings a third S1P modulator to the marketplace, and despite similar mechanisms of action, these are not identical agents. Each has its own unique features and advantages.

“Since the mid-1990s, we have seen the treatments for MS increase from the original three A-B-C medications to more than 20 approved brand-name and generic disease-modifying therapies to slow MS activity and progression. I am very optimistic about the approval of another new treatment for not only relapsing-remitting MS, but for clinically isolated syndrome and active secondary-progressive MS as well. 

“As noted in the article, Bristol Myers Squibb is delaying the launch of Zeposia due to the current COVID-19 pandemic in an effort to protect all those involved with the manufacture and marketing of this new medication. I support this decision and look forward to the launch of Zeposia once the coronavirus crisis has been resolved.”

For More Information

Individuals with questions may reach the BMS (Bristol Myers Squibb) Contact Center at the number and times listed below. This line will be staffed to answer all United States inquiries.

For general information or to speak with a trained Client Services Specialist, please call MSAA’s Helpline at (800) 532-7667, extension 154. Questions to MSAA’s Client Services department may also be emailed to MSquestions@mymsaa.org.

Written by Susan Wells Courtney, MSAA Senior Writer
Reviewed by Dr. Barry A. Hendin, MSAA Chief Medical Officer