Ozanimod aces in ulcerative colitis treatment
The oral selective sphingosine-1-phosphate (S1P) receptor modulator ozanimod induced significant improvements in clinical remission and response, which were sustained up to 52 weeks, in patients with moderate-to-severe ulcerative colitis (UC), according to the phase III True North study presented at AIBD 2020 Congress.
During the induction phase, 645 patients (mean age 42 years, 60 percent male, mean disease duration 7 years) in the double-blind cohort were randomized 2:1 to receive oral ozanimod HCl 1 mg once daily or placebo for 10 weeks. An additional 367 patients were included in the open-label cohort in which all received ozanimod HCl 1 mg for induction. [AIBD 2020, abstract P25]
At week 10, significantly more patients in the ozanimod group achieved the primary endpoint of clinical remission* compared with the placebo group (18.4 percent vs 6 percent; p<0.0001).
Clinical response** rate was also significantly higher with ozanimod than placebo (47.8 percent vs 25.9 percent; p<0.0001) at 10 weeks.
Significantly greater improvements with ozanimod vs placebo were also seen for other key secondary endpoints such as endoscopic improvement*** (27.3 percent vs 11.6 percent; p<0.0001) and mucosal healing# (12.6 percent vs 3.7 percent; p<0.001).
In addition, ozanimod led to significantly higher rates of histologic remission than placebo, regardless of the Geboes index score cut-points used (p<0.001 for all three cut-points).
When the analysis was stratified by prior exposure to tumour necrosis factor inhibitor (TNFi), improvements persisted for all clinical endpoints, with significant difference in favour of ozanimod among TNFi-naïve patients, while the difference was not significant for those who had previously received TNFi.
“The overall safety profile was consistent with the known safety profile for ozanimod and patients with moderately to severely active UC,” reported presenting author Dr Brian Feagan of Western University, Ontario, Canada.
Treatment-emergent adverse events (TEAEs) were reported in 40.1 percent of ozanimod-treated patients and 38 percent of those on placebo. The most common TEAEs were anaemia (4.2 percent vs 5.6 percent), followed by nasopharyngitis (3.5 percent vs 1.4 percent) and headache (3.3 percent vs 1.9 percent).
Cardiovascular events were infrequent, which included hypertension (1.4 percent vs 0 percent) and bradycardia (0.5 percent vs 0 percent). Serious infections were similarly rare, occurring in <1 percent in each group.
After the 10-week induction phase, responders were included into the subsequent 42-week maintenance study — whereby ozanimod responders were rerandomized to 1:1 to ozanimod or placebo, while placebo responders continued on placebo. [AIBD 2020, abstract P30]
Consistent with result of the induction phase, ozanimod led to significant and durable improvements which were clinically meaningful across all clinical, endoscopic, and histologic outcomes through 52 weeks.
“These results confirm the efficacy of an S1P receptor modulator in inflammatory bowel disease, even when using stringent definitions of mucosal healing and corticosteroid-free remission,” said the researchers.
Unlike the induction phase, improvements were significant regardless of whether patients had prior exposure to TNFi.
Also, the safety profile was consistent with previous findings, with no new safety signals reported.
“These findings support ozanimod as a potential treatment approach for patients with moderately to severely active UC,” the researchers concluded.
*defined as having the following on the 3-component Mayo score: rectal bleeding score (RBS)=0, stool frequency score ≤1 and decrease from baseline ≥1, and endoscopy subscore ≤1 without friability at week 10
**a reduction in 3-component Mayo score of ≥2 points and ≥35%, and reduction in RBS of ≥1 point or absolute RBS of ≤1 point
***mucosal endoscopy subscore ≤1 without friability
#mucosal endoscopy subscore ≤1 without friability plus histologic remission)