A poster featuring a post-hoc exploratory analysis of measures of thalamic volume from RADIANCE was presented September 11, 2019, at ECTRIMS 2019, the 35th Annual Congress of the European Committee for Treatment and Research in Multiple Sclerosis, taking place in Stockholm, Sweden.
Ozanimod, an oral immunomodulatory drug now under FDA review for the treatment of relapsing multiple sclerosis (MS), appears to be more effective than interferon β-1a (Avonex) at slowing disease activity, based on an established brain measure taken during phase 3 of the RADIANCE trial.
A poster featuring a post-hoc exploratory analysis of measures of thalamic volume (TV) from RADIANCE was presented September 11, 2019, at ECTRIMS 2019,1 the 35th Annual Congress of the European Committee for Treatment and Research in Multiple Sclerosis, taking place in Stockholm, Sweden.
The study authors noted that whole brain volume is a known measure of disease progression in relapsing MS, yet “evidence of the relationship between thalamic volume and disease activity in prospective, multicenter studies is sparse.” TV has been studied for years as a predictor of cognitive speed; a 2001 paper by Van Der Werf, et al, discussed how a decrease in TV “was apparent before the onset of loss of volume of the total brain.”2
Relapsing MS occurs when inflammation damages myelin, a fatty substance that insulates nerve cells, and thus allows interference with nerve impulses, triggering MS symptoms. Ozanimod works by selectively binding 2 receptors—the sphingosine 1-phosphate (S1PR1) and the S1PR5 receptors, which keeps immune cells from entering the brain and blocks inflammation of the central nervous system, so this inflammatory process does not occur.
The investigational therapy has been studied in 2 doses, 0.5 mg and 1.0 mg, in a pair of phase 3 trials, SUNBEAM and RADIANCE. The SUNBEAM trial featured 3 study arms: 1 arm each of patients taking the 2 doses of ozanimod and another taking interferon β-1a; full results of the 12-month study, first presented in 2017, were published last week in Lancet Neurology and show that ozanimod was well-tolerated and demonstrated a significantly lower relapse rate than interferon β-1a.3
RADIANCE was a 2-part trial to assess safety and efficacy of ozanimod compared with placebo. In the first part, 258 patients were randomly assigned to take 0.5 mg or 1.0 mg of the study drug or placebo once daily for 24 weeks. Patients taking ozanimod had fewer brain lesions after week 12, as measured by magnetic resonance imaging (MRI), as well as fewer relapses. During the second, open-label phase, 249 patients continued in the trial for 96 weeks. All those given ozanimod in the first phase stayed on their current dose, while those who had taken placebo were randomly assigned to either 0.5 mg or 1.0 mg. Both groups were free of disease activity and brain lesions after 24 months. Patients from the original placebo group had a large drop in relapses once they started taking ozanimod.4
RADIANCE offered an opportunity use TV measures taken at baseline to compare the effectiveness of the study drug, ozanimod, against interferon β-1A. Data presented Wednesday found that in patients with relapsing MS, smaller baseline TV is a sign of a higher disease burden and increased disease activity after 2 years, compared with those with higher baseline TV.1 Specifically, the data presented Wednesday showed:
US and European regulators are evaluating data from the multicenter, randomized, double-blind phase 2/3 RADIANCE and the phase 3 SUNBEAM trials, which were submitted in March. FDA accepted Celgene’s application for ozanimod June 6, 2019, and a decision is expected March 25, 2020.