• Ozanimod had a "beneficial effect" on cognitive processing speed
• The drug also reduced relapse rates and MRI lesions compared to Avonex
• Ozanimod is also in development for other immune-inflammatory indications including ulcerative colitis and Crohn's disease

Celgene Corporation (NASDAQ:CELG) announced on 10/10/18 the results of two post hoc analyses of data from the phase 3 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.

“Slowed cognitive processing, which is common in multiple sclerosis, often impairs quality of life for people living with this chronic condition,” said Bruce Cree, M.D., Ph.D., M.A.S., Professor of Neurology at the University of California San Francisco (UCSF) Weill Institute for Neurosciences, Clinical Research Director at the UCSF MS Center and an author of both analyses. “The findings from these new analyses suggest that, when compared to interferon, ozanimod has a beneficial effect on processing speed.”

“Slowed cognitive processing, which is common in multiple sclerosis, often impairs quality of life for people living with this chronic condition,” said Bruce Cree, M.D., Ph.D., M.A.S., Professor of Neurology at the University of California San Francisco (UCSF) Weill Institute for Neurosciences, Clinical Research Director at the UCSF MS Center and an author of both analyses. “The findings from these new analyses suggest that, when compared to interferon, ozanimod has a beneficial effect on processing speed.”

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 (≥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.

A previous pooled study analysis found that ozanimod did not reach statistical significance compared with IFN when analyzing the time to 3-month confirmed disability progression.

Ozanimod is a novel, oral, selective, sphingosine 1-phosphate 1 (S1P1) and 5 (S1P5) receptor modulator in development for immune-inflammatory indications including relapsing multiple sclerosis, ulcerative colitis and Crohn's disease.

Selective binding with S1P1 is believed to inhibit a specific sub set of activated lymphocytes from migrating to sites of inflammation. The result is a reduction of circulating T and B lymphocytes that leads to anti-inflammatory activity. Importantly, immune surveillance is maintained.

Selective binding with S1P5 is thought to activate specific cells within the central nervous system. This has the potential to enhance remyelination (when the body is able to repair damaged myelin after inflammation is reduced) and prevent synaptic defects. Ultimately, neurological damage may be prevented.

Celgene's application for ozanimod in MS was rejected by the FDA earlier this year. The FDA demanded additional data be added to the application. Celgene does not expect any delay in the application for IBD.