Basel, 18 May 2013
Roche's etrolizumab meets primary endpoint of clinical remission in moderate to severely active ulcerative colitis at week 10
Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the EUCALYPTUS phase II induction study of etrolizumab in patients with moderate-to-severely active ulcerative colitis (UC) met its primary endpoint of clinical remission at week 10. Additionally, the data showed etrolizumab was well tolerated with no clinically significant safety concerns. Findings were presented this weekend at the 2013 Digestive Disease Week meeting held in Orlando, Fla.
Ulcerative colitis is a chronic inflammatory condition of the colon and is characterized by mucosal ulceration, rectal bleeding, diarrhea, abdominal pain and may be complicated by severe bloody diarrhea and toxic megacolon, requiring major and sometimes urgent surgery. An estimated 900,000 people suffer from ulcerative colitis in the United States and Western Europe with 45 percent of UC cases diagnosed in people ages 15-44 in the United States.1
“These early data show the potential for etrolizumab to provide a much needed treatment option for these young patients,” said Richard Scheller, Ph.D., Head of Genentech Research and Early Development. “Etrolizumab, in a convenient subcutaneous monthly dosing, could significantly reduce the signs and symptoms of this debilitating disease.”
EUCALYPTUS phase II data showed significantly higher rates of clinical remission in patients treated with etrolizumab compared with placebo at week 10: 100 mg treatment group 20.5% of patients and 300 mg + loading dose (LD) treatment group 10.3% of patients versus placebo 0% (p=0.004 and 0.049 respectively). In the anti-TNF naïve subgroup, the rates of clinical remission at week 10 were significantly higher in the 100 mg treatment group compared with placebo (43.8% vs 0%, p=0.007). Full primary endpoint efficacy results are as follows:
|Etrolizumab 100 mg||Etrolizumab 300 mg + 420 mg LD||Placebo||Etrolizumab Pooled|
|No. (%) of patients||n=39 (16 aTNF-naïve/ 22 aTNF-IRa)||n=39 (12 aTNF-naïve/ 25 aTNF-IRa)||n=41 (15 aTNF-naïve/ 25 aTNF-IRa)|
n=78 (28 aTNF-naïve/ 47 aTNF-IRa)
|All comers||8 (20.5%)***||4 (10.3%)*||0||12 (15.4%)**|
|Anti-TNF-naïve||7 (43.8%)**||3 (25%)||0||10 (35.7%)**|
|Anti-TNF-IR||1 (4.5%)||1 (4%)||0||2 (4.3%)|
a4 patients distributed across the treatment groups are anti-TNF exposed but are not anti-TNF-inadequate responders (IR)
Clinical remission (* p<0.05, ** p<0.01, *** p<0.005 vs placebo)
About the EUCALYPTUS study
EUCALYPTUS is a phase II randomized, double blind, placebo-controlled induction study to evaluate efficacy and safety in patients with refractory moderate-to-severely active ulcerative colitis. The primary efficacy endpoint was the proportion of patients in clinical remission at week 10. Patients (n=124) were randomized to two dose levels of etrolizumab (100 mg monthly subcutaneous (SC) or 300 mg monthly SC + loading dose of 420 mg SC between week 0 and 2) or placebo for three doses. Concomitant therapy for ulcerative colitis remained stable for a minimum of eight weeks.
Rates of adverse events were lower in the etrolizumab treatment groups compared with the placebo group. There were no serious infections in the etrolizumab treatment groups. One etrolizumab treated patient suffered a rash and headache after the first dose and was admitted to hospital for observation. This patient was negative for anti-therapeutic antibodies. There were a total of four actively treated patients with mild (Grade 1) injection site reactions all of whom were in the 300 mg + load dosing group. The following are more details on adverse events:
|Etrolizumab 100 mg||Etrolizumab 300 mg + LD||Placebo||Etrolizumab Pooled|
|No. (%) of patients||n=41||n=40||n=43||n=81|
|Any AE||31 (75.6%)||25 (62.5%)||34 (79.1%)||56 (69.1%)|
|Drug-related AE||16 (39%)||12 (30%)||14 (32.6%)||28 (34.6%)|
|AE resulting in discontinuation||2 (4.9%)||1 (2.5%)||4 (9.3%)||3 (3.7%)|
|Serious AEs||5 (12.2%)||2 (5%)||6 (14%)||7 (8.6%)|
|Serious infection AEs||0||0||1 (2.3%)||0|
About ulcerative colitis disease
Ulcerative colitis (UC) is a chronic inflammatory condition of the colon with the potential for extraintestinal manifestations. UC is characterized by mucosal ulceration, rectal bleeding, diarrhea, and abdominal pain and may be complicated by severe bloody diarrhea and toxic megacolon, requiring major and sometimes urgent surgery. 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 the incidence and prevalence vary between regions of the world, both have been rising, which may be due in part 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.
Etrolizumab is a humanized, monoclonal antibody targeting the Beta7 integrin subunit of the heterodimers alpha4beta7 (α4β7) and alphaEbeta7 (αEβ7), inhibiting the interaction of these integrins with their respective ligands MAdCAM-1 and E-cadherin. The hypothesis is that the inhibition of binding of αEβ7 to E-cadherin will provide superior efficacy to the inhibition of binding of α4β7 to MAdCAM-1 alone.
About Roche in immunology
The Roche Group’s immunology medicines include rheumatoid arthritis treatments MabThera®/Rituxan®(rituximab) and ACTEMRA®/RoACTEMRA® (tocilizumab), XOLAIR® (omalizumab) in asthma, and Pulmozyme® (dornase alfa) for cystic fibrosis. In addition to its approved portfolio of immunology medicines, Roche pipeline products include etrolizumab, being studied in ulcerative colitis, and lebrikizumab for severe asthma.
Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, infectious diseases, inflammation, metabolism and neuroscience.
Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2012 Roche had over 82,000 employees worldwide and invested over 8 billion Swiss francs in R&D. The Group posted sales of 45.5 billion Swiss francs. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.
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1. Herrinton, L et al. American Journal of Gastroenterology 2008; 1998-2006.