In patients with moderate to severe ulcerative colitis, histologic improvement was greater with ozanimod 1 mg versus placebo at weeks 8 and 32
A greater proportion of patients achieved histologic remission at week 32 with ozanimod 1 mg versus placebo
Data shared in oral presentation at the 11th
"It's exciting to observe histologic improvements in patients with ulcerative colitis who were treated with ozanimod. Clinical research suggests that histologic improvements can be linked with improved clinical outcomes in ulcerative colitis," said Dr. William Sandborn, M.D., Professor of Medicine and Chief, Division of Gastroenterology and Director, University of California San Diego Inflammatory Bowel Disease Center. "While often more difficult to measure, endpoints such as histologic improvement or remission are emerging as important treatment goals for patients and their physicians."
TOUCHSTONE evaluated the efficacy and safety of 0.5 mg and 1 mg doses of ozanimod compared with placebo after eight weeks of treatment (induction phase) in 197 patients with moderate to severe active ulcerative colitis. Patients who achieved a clinical response at week 8 continued with their original treatment through week 32 in a maintenance phase. The primary endpoint was the proportion of patients in remission at week 8. Secondary endpoints were: the proportion of patients achieving a clinical response, the proportion of patients with mucosal improvement and the change from baseline in Mayo score. Histologic improvement and remission with ozanimod at the same time points was assessed as an exploratory endpoint. Biopsies were scored by a central pathologist blinded to treatment and sequence. Previously reported results showed TOUCHSTONE met its primary endpoint and secondary endpoints with statistical significance for patients on the 1 mg dose of ozanimod versus placebo.
In the histology results from the TOUCHSTONE study presented at ECCO, histologic improvement, which was determined by assessing the change from baseline in Geboes score (12.92 in ozanimod 1 mg, 14.36 in ozanimod 0.5 mg and 13.94 placebo; a decrease in absolute score indicates an improvement), was significantly greater for the 1 mg dose than for placebo at both week 8 [Geboes (-4.37 vs. -2.20, p=0.0345)] and week 32 [Geboes (-5.50 vs. -2.24, p=0.0033)]. The 0.5 mg dose resulted in greater improvement than placebo but the difference did not reach statistical significance at either time point.
At week 8, although there was an apparent numerical dose response in the proportion of patients reaching histologic remission, defined as a Geboes score less than 2, there were no significant differences. However at week 32, 31 percent (21/67) of patients on ozanimod 1 mg achieved histologic remission compared with 8 percent (5/65) on placebo (p=0.0006), and 23 percent (15/65) of patients on ozanimod 0.5 mg achieved histologic remission (p=0.0164 vs. placebo).
Adverse events (AEs) from the phase 2 study occurred in 26/67 (38.8 percent) patients in the ozanimod 1 mg arm, 26/65 (40.0 percent) in the ozanimod 0.5 mg arm and 26/65 (40.0 percent) in the placebo arm. The most common AEs were worsening of ulcerative colitis (3, 2 and 5 patients in the arms outlined above, respectively) and anemia (0, 3 and 4 patients in the arms outlined above, respectively). No AEs of special interest (cardiac, pulmonary, ophthalmologic, hepatic or serious infection) were reported during the induction or maintenance phase.
"These data suggest that in addition to benefits we've previously seen,
oral ozanimod could also help ulcerative colitis patients achieve the
important treatment goal of histologic remission," said
About the Trial
TOUCHSTONE is a phase 2, randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of ozanimod (also known as RPC1063) with placebo in patients with moderate to severe active ulcerative colitis. A total of 197 patients were randomized and treated once daily with 1 mg ozanimod (n=67), 0.5 mg ozanimod (n=65) or placebo (n=65) for 8 weeks (the induction phase). The primary endpoint was the proportion of patients in remission (Mayo score ≤2, no subscore > 1) at week 8. Secondary endpoints were the proportion of patients achieving clinical response (reduction in Mayo score of ≥3 and ≥30% with a decrease in the rectal bleeding score of ≥1 or a rectal bleeding score ≤1), proportion of patients with mucosal improvement (endoscopy score ≤1, and the change in Mayo score. Safety assessments included ECG, Holter monitoring, pulmonary function testing, optical coherence tomography and adverse events.
For the maintenance phase, patients who achieved a clinical response at week 8 continued with their original treatment through week 32.
Ozanimod is a small molecule sphingosine 1-phosphate 1 and 5 receptor modulator in development for immune-inflammatory indications including relapsing multiple sclerosis and inflammatory bowel disease. Treatment with S1P receptor modulators is believed to work by interfering with S1P signaling and blocking the response of lymphocytes (a type of white blood cell) to exit signals from the lymph nodes, sequestering them within the nodes. The result is a reduction of circulating lymphocytes that leads to anti-inflammatory activity by inhibiting migration of pathologic lymphocytes to sites of inflammation.
Ozanimod is an investigational compound that is not approved for any use in any country.
About Ulcerative Colitis
Ulcerative colitis is a chronic, relapsing condition triggered by an
abnormal, prolonged immune response that creates long-lasting
inflammation and ulcers (sores) in the mucosa (lining) of the large
intestine (colon). Symptoms usually develop over time, rather than
suddenly. The disease can be debilitating and can sometimes lead to
life-threatening complications. Ulcerative colitis is the most common
form of inflammatory bowel disease worldwide. About one in every 198
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