New analyses from pivotal Phase III trials of oral ozanimod for relapsing multiple sclerosis . Celgene

Celgene Corporation announced the results of two post hoc analyses of data from the phase III SUNBEAM and RADIANCE Part B trials which evaluated the efficacy and safety of ozanimod, a novel, oral, selective sphingosine 1-phosphate 1 (S1P1) and 5 (S1P5) receptor modulator, versus a first-line treatment, Avonex (interferon beta-1a) (IFN), in patients with relapsing multiple sclerosis (RMS). These findings will be presented at ECTRIMS 2018.

SUNBEAM evaluated two doses (0.92 mg and 0.46 mg, equivalent to 1 mg and 0.5 mg ozanimod HCI respectively) of oral ozanimod in 1,346 patients with RMS treated for at least one year. A post hoc analysis of 12-month data from SUNBEAM to be presented today examined the effect of ozanimod on cognitive processing speed, based on performance on the Symbol Digit Modalities Test (SDMT). Benefits in SDMT score at month 12 were seen with ozanimod versus IFN (difference: 1.6; 95% confidence interval [CI]: 0.62, 2.56 for ozanimod 1 mg and 1.2; 95% CI: 0.19-2.13 for ozanimod 0.5 mg). More patients exhibited clinically meaningful ( greater than 4-point) improvements in processing speed at month 12 with ozanimod 1 mg (rate ratio, 1.3; 95% CI: 1.05, 1.55) and 0.5 mg (1.2; 95% CI: 0.94, 1.40) versus IFN. A second post hoc analysis on annualized relapse rates (ARR) and MRI lesions examined the effect of ozanimod in patients with early RMS compared with patients with more advanced disease. Early RMS was defined based on a composite baseline profile, including 3 years or less since diagnosis, an Expanded Disability Status Scale (EDSS) of 3.5 or less, and the use of one or no disease-modifying treatments. In the pooled phase 3 studies, two doses of oral ozanimod (1 mg and 0.5 mg) were evaluated compared with IFN in 2,659 patients treated for two years. For patients with early RMS (n=1,392) in this analysis, ARR was lower at 12 months with ozanimod 1 mg (ARR=0.149) and ozanimod 0.5 mg (ARR=0.200) compared with IFN (ARR=0.285). ARR was also lower with ozanimod versus IFN in patients with more advanced RMS (n=1,267) (ozanimod 1 mg: 0.217; 0.5 mg: 0.277; IFN: 0.363).Ozanimod also showed a reduction of MRI lesions in both early and more advanced RMS in this analysis. For patients with early RMS, the mean number of gadolinium-enhancing (GdE) lesions at 12 months was 0.263 with ozanimod 1 mg, 0.458 with ozanimod 0.5 mg and 0.656 with IFN. For those with more advanced RMS, the mean number of GdE lesions was 0.278, 0.323 and 0.915, respectively. Similarly, the mean number of new or enlarging T2 lesions at 12 months for patients with early RMS was 2.952 for ozanimod 1 mg, 3.744 for ozanimod 0.5 mg and 4.633 for IFN. For patients with more advanced RMS, the numbers were 2.514, 2.903 and 4.710, respectively.

In the SUNBEAM and RADIANCE clinical trials, the most common adverse reactions ( greater than 5 percent) that were higher with ozanimod than with IFN were upper respiratory tract infections, urinary tract infections, increases of alanine aminotransferase and increases of gamma-glutamyl transferase.