Date: 2013-05-16
Type of information: Initiation of preclinical development
phase: 2
Announcement: presentation of results at the 2013 Digestive Disease Week meeting held in Orlando
Company: Roche (Switzerland)
Product: etrolizumab
Action
mechanism: monoclonal antibody. Etrolizumab is a humanized, monoclonal antibody targeting the Beta7 integrin subunit of the heterodimers alpha4beta7 (a4ß7) and alphaEbeta7 (aEß7), inhibiting the interaction of these integrins with their respective ligands MAdCAM-1 and E-cadherin. The hypothesis is that the inhibition of binding of aEß7 to E-cadherin will provide superior efficacy to the inhibition of binding of a4ß7 to MAdCAM-1 alone.
Disease: moderate-to-severely active ulcerative colitis
Therapeutic area: Autoimmune diseases - Inflammatory diseases
Country:
Trial
details: 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.
Latest
news: Summary of Primary Efficacy Results at Week 10 in EUCALYPTUS No. (%) of patients Etrolizumab 100 mg n=39 16 aTNF-naïve/ 22 aTNF-IRa Etrolizumab 300 mg + 420 mg LD n=39 12 aTNF-naïve/ 25 aTNF-IRa Placebo n=41 15 aTNF-naïve/ 25 aTNF-IRa Etrolizumab Pooled 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%) Summary of Adverse Events at 10 Weeks in EUCALYPTUS No. (%) of patients Etrolizumab 100 mg n=41 Etrolizumab 300 mg + LD n=40 Placebo n=43 Etrolizumab Pooled n=81 Any AE 31 (75.6%) 25 (62.5%) 34 (79.1%) 56 (69.1%)* On May 16, 2013, Roche has announced 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.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:
a) 4 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 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.
