Celgene International Sàrl, a wholly owned subsidiary of Celgene Corporation (NASDAQ: CELG), today announced that additional data of exploratory endpoints from the TOUCHSTONE phase 2 clinical trial of ozanimod in patients with moderate to severe ulcerative colitis were presented at the 11th Congress of the European Crohn’s and Colitis Organisation (ECCO) in Amsterdam. Ozanimod is an investigational selective S1P 1 and 5 receptor modulator. These results, included in a digital oral presentation, showed that ozanimod 1 mg resulted in improvements in histologic features and remission in patients treated over 32 weeks.
“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 Scott Smith, President, Celgene Inflammation & Immunology. “We are committed to bringing innovative medicines and different treatment options for patients with inflammatory bowel disease and continue to actively advance the phase 3 clinical program for ozanimod.”
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 people in Europe, and one in every 402 people in North America, have ulcerative colitis. In 2004, 2.1 million prescriptions were written to treat ulcerative colitis, and 716,000 ambulatory care visits were related to the disease. In 2010, there were 107,000 hospitalizations due to ulcerative colitis.
Celgene International Sàrl, located in Boudry, Switzerland, is a wholly owned subsidiary and international headquarters of Celgene Corporation. Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit www.celgene.com. Follow Celgene on Social Media: @Celgene, Pinterest, LinkedIn, FaceBook and YouTube.
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