Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Evaluate The Efficacy (Maintenance Of Remission) And Safety Of Etrolizumab Compared With Placebo In Patients With Moderate To Severe Active Ulcerative Colitis Who Are Naive To TNF Inhibitors.

Althoughthere are therapeutic options including anti-TNF agents, a significantproportion of patients with UC will not experience a durable clinical benefitwith those treatment options. Furthermore, adverse events associated withanti-TNFs include elevated rates of serious bacterial infection, including TB,and (more rarely) lymphoma and demyelination (Chang and Lichtenstein 2006). Nocurrently available therapy achieves sustained remission in more than 10%−30%of patients with IBD who have chronic disease(Hanauer et al. 2002; Sandborn et al. 2005). As noted above, etrolizumab distinguishesitself from other anti-integrins on the basis of gut selectivity combined with apotential dual mechanism of action. It binds αEβ7 in addition to α4β7 and soregulates retention as well as trafficking leukocyte/lymphocyte in theintestinal mucosa.

In summary, favorablesafety (see Section 1.2) and efficacy data were observed in the Phase IIEUCALYPTUS study and in the OLE study (SPRUCE). Overall, etrolizumab showedcompelling efficacy compared with placebo and there were no clinically significantsafety signals. Additionally, etrolizumab distinguishes itself from vedolizumabby blocking αEβ7 in addition to α4β7, which is involved in lymphocyte retentionand may contribute to its efficacy and/or safety profile. Etrolizumab is a gut-selective anti-traffickingagent and does not bind to α4β1 (target for natalizumab), which regulates traffickingto both mucosal and non-mucosal tissues, including the CNS. Although natalizumabhas been associated with an increased risk of PML, no events of PML to datehave been reported during 2-year PML extensive monitoring in the Phase IIstudy, EUCALYPTUS, and OLE SPRUCE study.