Roche has announced that phase II clinical data published in The Lancet shows clinical remission in 43.8 percent (p=0·007) of patients with moderate-to-severe ulcerative colitis (UC), a type of inflammatory bowel disease. This remission rate occurred in anti-TNF naïve patients at 10 weeks in the 100 mg dose arm and has the potential to provide one of the highest remission rates of current treatment options. In a post hoc analysis, a subpopulation of patients with high alphaE-beta7 in colon biopsy showed even greater clinical remission rates. This potential predictive biomarker will be studied in phase III trials. In addition, the safety profile showed no significant concerns.
Ulcerative colitis is a chronic inflammatory condition of the colon, characterized by mucosal ulceration, rectal bleeding, diarrhea and abdominal pain. In complicated cases it may require major, and sometimes urgent, surgery. Many patients who don't respond to current treatments have an increased risk of serious infection and cancer.1,2 An estimated 900,000 people suffer from ulcerative colitis in the United States (US) and Western Europe with 45 percent of UC cases diagnosed in people ages 15-44 in the US.3
"Despite available treatment options, there is a high unmet need for new therapies offering treatment with higher rates of sustained remission for these young patients - whether they are newly diagnosed or have failed to respond to anti-TNFs," said Dr. Séverine Vermeire, University Hospitals Leuven, Belgium. "Etrolizumab, with convenient subcutaneous monthly dosing, could potentially offer hope for patients with this debilitating disease."
Etrolizumab is an unlicensed medicine and is still being investigated in clinical trials. A phase III program in inflammatory bowel disease investigating etrolizumab in ulcerative colitis and also in Crohn's disease comprising more than 3,500 patients is expected to begin in the first half of 2014.
About the EUCALYPTUS study
EUCALYPTUS is a phase II clinical trial that evaluated the efficacy and safety of etrolizumab in patients with moderate-to-severe ulcerative colitis who failed conventional therapy and/or anti-TNFs. The primary efficacy endpoint was clinical remission at week 10, defined as a total Mayo Clinical Score of ≤ 2 with no individual subscore > 1. Forty centres in 11 countries randomized 124 patients to two dose levels of etrolizumab (100 mg monthly subcutaneous (SC) (n=41) or 300 mg monthly SC + loading dose of 420 mg SC between week 0 and 2 (n=40)) or placebo (n=43) for three doses. Concomitant therapy for ulcerative colitis remained stable for a minimum of eight weeks.
Higher rates of rash, influenza-like illness, and arthralgias were observed in patients treated with etrolizumab; all of these events were considered mild to moderate in severity. Serious adverse events were reported in 12 patients; five of these were related to ulcerative colitis. No serious opportunistic infections were reported. Mild injection site reactions occurred in four patients in the etrolizumab 300-mg plus LD group and in two patients receiving placebo.
Etrolizumab is a gut-selective monoclonal antibody targeting the anti-beta7 integrin, inhibiting both the alpha4-beta7 and alphaE-beta7 integrins. Other gut selective anti-integrins in clinical development inhibit only alpha4-beta7 integrin. Targeting alphaE-beta7 may confer added efficacy, which will be evaluated in the etrolizumab phase III program. Further investigation in phase III trials will evaluate the hypothesis that alphaE level predicts clinical response to etrolizumab treatment. The most common adverse events were mild to moderate in nature and included injection site reactions (in the etrolizumab 300 mg + loading dose treatment group only), rash, arthralgias and flu-like symptoms.
About ulcerative colitis disease
UC represents dysregulation of the mucosal immune system in genetically susceptible individuals in response to commensal microbiota and other environmental triggers. The overall incidence of UC ranges from 6.3 to 24.3 cases per 100,000 persons per year, and prevalence ranges from 4.9 to 505.0 cases per 100,000 persons, with the highest estimates in Western European and North American populations. Although incidence and prevalence varies across different regions of the world, prevalence is mainly expected to rise due to better detection and diagnosis, and Westernization of diet. The disease can affect any age group, but diagnosis peaks between the ages of 15 and 35 years.4
Adverse event reporting
Reporting suspected adverse events after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Roche is committed to the safety of its medicines. As such Roche encourages adverse events to be reported and hence the inclusion of this explanatory information. Adverse events should be reported. Reporting forms and information can be found at http://www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Roche Products Ltd. Please contact Roche Drug Safety Centre by emailing firstname.lastname@example.org or calling +44(0)1707 367554.