Ozanimod Shows Strong Relapse Reductions for RMS in SUNBEAM Study

Giancarlo Comi, MD. Professor of Neurology Vita-Salute San Raffaele University Milan, Italy

Giancarlo Comi, MD

Treatment with ozanimod significantly reduced annualized relapse rates (ARR) at 1 year and showed marked reductions in new or enlarging T2 lesions on MRIs compared with interferon beta-1a (IFN) for patients with relapsing multiple sclerosis (RMS), according to findings from the phase 3 SUNBEAM study presented at the 2017 MS Paris Meeting.

In the trial, which explored two doses of ozanimod, the ARR was 0.350 with IFN compared with 0.241 and 0.181, representing a 31% (P = .0013) and a 48% (P <.0001) improvement in ARR for ozanimod at 0.5 mg and 1.0 mg, respectively. Additionally, when compared with IFN, there was a 25% (P = .0032) and a 48% (P <.0001) reduction in the development of new/enlarging T2 lesions for ozanimod at 0.5 and 1.0 mg, respectively.

"Both ozanimod doses demonstrated superiority to interferon on ARR and MRI endpoints, and a dose response was consistently demonstrated across these efficacy endpoints," lead investigator Giancarlo Comi, MD. Professor of Neurology Vita-Salute San Raffaele University Milan, Italy. "Overall, ozanimod was generally safe and well tolerated. These efficacy and safety results demonstrate a favorable benefit-risk profile for ozanimod in RMS."

In the SUNBEAM trial, patients were randomized to receive ozanimod at 1 mg (n = 448), 0.5 mg (n = 451), or IFN at 30 mcg (n = 447). Patients had a mean age of 36 years and two-thirds were female. The baseline expanded disability status scale (EDSS) score was 2.5 and about one-third of patients had received prior disease modifying therapy (DMT).

At 1 year, there was a mean of 2.836 new or enlarging T2 lesions for those treated with IFN compared with 2.139 and 1.465 in the 0.5 and 1.0 mg ozanimod groups, respectively. Additionally, ozanimod demonstrated marked improvements at slowing brain volume loss compared with IFN.

Overall, IFN showed a -0.570 reduction in whole brain volume compared with -0.500 and -0.385 for the 0.5 and 1.0 mg doses of ozanimod, representing a 12% (P = .0615) and a 33% (P <.0001) improvement, respectively. There was a -0.985 change in median cortical gray matter volume with IFN compared with -0.380 and -0.160 for the 0.5 and 1.0 mg doses of ozanimod, respectively, representing a 61% (P <.0001) and an 84% (P <.0001) improvement.

Thalamic volume loss was also improved with ozanimod compared with IFN (-1.560 for IFN versus -1.025 and -0.960 for the 0.5 and 1.0 mg doses, respectively). There was a 34% (P <.0001) and a 39% (P <.0001) improvement over IFN in thalamic loss with the 0.5 and 1.0 mg doses, respectively.

Confirmed disability progression (CDP) at 3 months was 0.045 with IFN and 0.039 and 0.030 for the 0.5 mg and 1.0 mg doses of ozanimod, respectively. In a combined analysis of the SUNBEAM study and the phase 3 RADIANCE trial, which also explored ozanimod compared with IFN, there was not a statistically significant different between the groups for CDP; however, there were few progression events at the time of the analysis.

Overall, an adverse event (AE) of any grade was more common with IFN (75.5%) than for ozanimod at 0.5 mg (57.2%) or 1.0 mg (59.8%). The rates of serious AEs were similar between groups. The most common events with ozanimod were nasopharyngitis, headache, and upper respiratory tract infection compared with influenza like symptoms, nasopharyngitis, headache, and upper respiratory infection for IFN.

Overall, there were few cardiac events seen with ozanimod, with a mean supine heart rate reduction of -1.8 beats per minute at hour 5 following treatment. There were no signs of 2nd degree or higher atrioventricular block. "Serious cardiac AEs were infrequent and balanced across treatment groups," Comi said. "Infection SAEs were infrequent and balanced across treatment groups. No serious opportunistic infections were reported," he added.

Based on findings from the SUNBEAM and RADIANCE trials, Celgene, the company developing ozanimod, announced plans to submit a new drug application to the FDA for patients with RMS. This application is expected by the end of 2017, according to a statement from the company released earlier this year.

Comi G, Kappos L, Selmaj K, et al. Ozanimod demonstrates efficacy and safety in a phase 3 trial of relapsing multiple sclerosis (SUNBEAM). Presented at: 7th Joint ECTRIMS - ACTRIMS Meeting; October 25-28, 2017, Paris, France. Abstract 232.