SUMMARY:
- Results of two phase III trials of oral ozanimod (Celgene Corporation) have been published. In both studies, ozanimod significantly reduced the relapse rate compared with Avonex® (interferon beta-1a, Biogen), and also reduced MRI-detected disease activity and brain atrophy. Ozanimod appeared to be well-tolerated during the studies.
- Both phase III studies were the bases of an application submitted to the U.S. Food and Drug Administration for approval of ozanimod to treat relapsing MS. This application was accepted in June 2019.
- Giancarlo Comi, MD (San Raffaele Scientific Institute, Milan) and colleagues worldwide published SUNBEAM results in the Lancet Neurology (Published September 3, 2019). Jeffrey Cohen, MD (Cleveland Clinic) and colleagues worldwide published RADIANCE results in the Lancet Neurology (Published September 3, 2019)
DETAILS
Background: Ozanimod is a selective sphingosine 1-phosphate receptor modulator. It is thought to act by promoting the retention of certain white blood cells in the body’s lymph nodes, keeping them out of circulation and from entering the brain and spinal cord. Similar therapies are approved by the FDA to treat MS: Gilenya
® fingolimod, Novartis International AG) and Mayzent
® (siponimod, Novartis International AG). In an earlier phase II trial, in 258 participants with relapsing MS, disease activity on MRI scans was reduced in people taking two different doses of ozanimod, compared to people taking placebo. (
Lancet Neurology, 2016 Apr;15(4):373-81)
SUNBEAM Study: For this phase III trial, 1,346 participants were randomly assigned to one of three treatment groups, taking either daily oral ozanimod (0.5 mg) and an inactive placebo injected into muscle once weekly; daily oral ozanimod (1 mg) and inactive placebo injected into muscle once weekly; or Avonex and an oral placebo daily for 12 months. The primary outcome was relapse rate, measured at 12 months. Secondary outcomes included disease activity as observed on MRI scans, and measures of brain tissue volume.
The study met the primary endpoint in reducing relapse rates, as well as the secondary MRI endpoints. Both doses of ozanimod significantly reduced the loss of brain tissue volume more than Avonex. No cardiac-related side effects were observed during dose escalation in participants treated with ozanimod. No serious infections occurred in the ozanimod group. Increases in liver enzymes occurred across all groups, and resulted in two participants discontinuing ozanimod. Other safety findings are detailed in the open-access papers.
RADIANCE Study: For the second phase III trial, 1,313 participants were randomly assigned to one of three treatment groups, taking either daily oral ozanimod (0.5 mg) and an inactive placebo injected into muscle once weekly; daily oral ozanimod (1 mg) and inactive placebo injected into muscle once weekly; or Avonex and an oral placebo daily for 24 months.
The study met the primary endpoint in reducing the relapse rate over two years, as well as the secondary MRI measures of disease activity. Both doses of ozanimod significantly reduced the loss of brain tissue volume more than Avonex. Four participants experienced a transient reduced heart rate. No serious infections occurred. Other safety findings are detailed in the open-access papers.
In a pooled analysis of both phase III studies, ozanimod was not shown to slow disability progression significantly more than Avonex.
Giancarlo Comi, MD (San Raffaele Scientific Institute, Milan) and colleagues worldwide published SUNBEAM results in the Lancet Neurology (
Published September 3, 2019). Jeffrey Cohen, MD (Cleveland Clinic) and colleagues worldwide published RADIANCE results in the Lancet Neurology (
Published September 3, 2019)
Conclusions: Both phase III studies suggest that ozanimod can reduce MS disease activity, and the results were the bases of an application submitted to the U.S. Food and Drug Administration for approval of ozanimod to treat relapsing MS. This application was accepted in June 2019.
In an accompanying editorial, Ellen Mowry, MD (Johns Hopkins) and John Corboy, MD (University of Colorado) comment that more real-world data are necessary to determine the safety and effectiveness of ozanimod in a broader range of people with MS, including people in whom risks may be greater because of advanced age or disability. However, they say, the results of these studies “provide reassurance about the clinical efficacy and safety outcomes” of this class of medication.
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Avonex is a registered trademark of Biogen
Gilenya is a registered trademark of Novartis
Mayzent is a registered trademark of Novartis