BACKGROUND: Ozanimod (RPC1063) is an oral agonist of the sphingosine-1-phosphate 
receptor subtypes 1 and 5 that induces peripheral lymphocyte sequestration, 
potentially decreasing the number of activated lymphocytes circulating to the 
gastrointestinal tract.
METHODS: We conducted a double-blind, placebo-controlled phase 2 trial of 
ozanimod in 197 adults with moderate-to-severe ulcerative colitis. Patients were 
randomly assigned, in a 1:1:1 ratio, to receive ozanimod at a dose of 0.5 mg or 
1 mg or placebo daily for up to 32 weeks. The Mayo Clinic score was used to 
measure disease activity on a scale from 0 to 12, with higher scores indicating 
more severe disease; subscores range from 0 to 3, with higher scores indicating 
more severe disease. The primary outcome was clinical remission (Mayo Clinic 
score ≤2, with no subscore >1) at 8 weeks.
RESULTS: The primary outcome occurred in 16% of the patients who received 1 mg 
of ozanimod and in 14% of those who received 0.5 mg of ozanimod, as compared 
with 6% of those who received placebo (P=0.048 and P=0.14, respectively, for the 
comparison of the two doses of ozanimod with placebo). Differences in the 
primary outcome between the group that received 0.5 mg of ozanimod and the 
placebo group were not significant; therefore, the hierarchical testing plan 
deemed the analyses of secondary outcomes exploratory. Clinical response 
(decrease in Mayo Clinic score of ≥3 points and ≥30% and decrease in 
rectal-bleeding subscore of ≥1 point or a subscore ≤1) at 8 weeks occurred in 
57% of those receiving 1 mg of ozanimod and 54% of those receiving 0.5 mg, as 
compared with 37% of those receiving placebo. At week 32, the rate of clinical 
remission was 21% in the group that received 1 mg of ozanimod, 26% in the group 
that received 0.5 mg of ozanimod, and 6% in the group that received placebo; the 
rate of clinical response was 51%, 35%, and 20%, respectively. At week 8, 
absolute lymphocyte counts declined 49% from baseline in the group that received 
1 mg of ozanimod and 32% from baseline in the group that received 0.5 mg. The 
most common adverse events overall were anemia and headache.
CONCLUSIONS: In this preliminary trial, ozanimod at a daily dose of 1 mg 
resulted in a slightly higher rate of clinical remission of ulcerative colitis 
than placebo. The trial was not large enough or of sufficiently long duration to 
establish clinical efficacy or assess safety. (Funded by Receptos; TOUCHSTONE 
ClinicalTrials.gov number, NCT01647516.).