Ozanimod (formerly RPC1063)
Experimental Medications: New S1P Receptor Modulators
Company: Celgene
- Oral medication studied at several doses
- Being studied in RMS
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Ozanimod (RPC1063) is a selective modulator of two types of S1P receptors: S1P1 and S1P5. The once-daily pill was studied in a trial called RADIANCE, where the experimental medicine was compared at two different doses with placebo. A total of 258 individuals with relapsing forms of MS (RMS) were studied in this trial, which began with a seven-day gradual titration of ozanimod up to the full investigational dose. (Titration refers to starting with a lower dose and gradually increasing until the full dose is reached. This helps reduce the risk of side effects when starting a new medication.) The double-blind study ran for 24 weeks, followed by a year-long safety-extension period.
At the end of the initial 24-week treatment period, individuals in both groups taking ozanimod showed an 86-percent decrease in the cumulative number of gadoliniumenhanced lesions compared to the placebo group. The relapse rates also decreased in the treatment groups compared with placebo, with a 31-percent decrease in the 0.5-mg group and a 53-percent decrease in the 1-mg group.
The most common side effects reported were nasopharyngitis (the common cold) and headache. However, both of these events were reported more commonly by placebotreated individuals than by ozanimod-treated participants. Notably, none of the subjects receiving ozanimod experienced serious cardiac events, infections, or episodes of macular edema (a buildup of fluid in the retina that can cause vision loss. It can occur in rare cases with use of Gilenya).64
In 2016, the 72-week extension data of the RADIANCE trial were released. These data showed a continued reduction in relapses and gadolinium-enhancing lesions for those individuals who remained on ozanimod, with efficacy results favoring the 1- mg dose over the lower 0.5-mg dose. No new safety or tolerability issues were identified during this blinded extension phase of the trial.
Celgene, the company that is developing ozanimod, has submitted a New Drug Application asking the United States Food and Drug Administration to approve ozanimod for the treatment of RMS. Celgene has also submitted a Marketing Authorization Application to the European Medicines Agency for the same indication. Pivotal data from RADIANCE and from another Phase III study, SUNBEAM, were included in both applications.5, 65
More recently, SUNBEAM and RADIANCE data showed dose-dependent improvements in relapse frequency and MRI-measured disease activity in individuals with early or advanced RMS. A total of 2,659 patients, including 1,267 with advanced RMS, received either daily ozanimod 0.5 mg or 1 mg or weekly interferon beta-1a injections (30 mcg) for one to two years. The median time since MS diagnosis was 0.5 years for the early RMS group and 5.7 years for the advanced RMS group.
After one year, the mean number of T1-enhancing lesions and T2 new and enlarging lesions were lower among participants who received the higher ozanimod dose versus the lower dose, but both groups had significantly fewer lesions than the participants who were treated with interferon. Ozanimod improved all measures of disease activity among both the early and advanced RMS groups.66
Overall relapse rates were 42 percent and 26 percent lower among the ozanimod 1 mg and 0.5 mg groups, respectively, compared with interferon-treated group. Relapses that required hospitalization or treatment with steroids decreased by 43 percent and 26 percent in the ozanimod 1 mg and 0.5 mg groups, respectively. The incidence of acute relapses was 20 percent to 35 percent lower among ozanimod-treated patients compared with interferon.67
Ozanimod also was shown in the SUNBEAM trial to prevent or delay cognitive deficits. MS can slow “processing speed” (the time needed to perform a mental task). Slowed processing speed can make executive functions such as paying attention and making decisions more difficult, and can impair the quality of life for individuals with MS.
More than 1,300 people who received ozanimod 1 mg or 0.5 mg or intramuscular interferon beta-1a were studied in an analysis in which researchers administered the Symbol Digit Modalities Test (SDMT), which measures cognitive impairment, at baseline, six months, and one year. Improvements in SDMT scores of 4 points or greater were more common among the participants in both ozanimod-treatment groups than among those treated with interferon. A 4-point SDMT increase signifies clinically meaningful improvement in processing speed, and these improvements were seen six months and one year after baseline testing among individuals receiving ozanimod.68