Roche Reports Mixed Phase III Results for Etrolizumab in Ulcerative Colitis, with Maintenance Studies Missing Primary Endpoints

Compiled by Keke

Recently, Genentech, a member of the Roche Group, released the top-line data from its Phase 3 clinical trial program evaluating the efficacy of its investigational drug etrolizumab in patients with moderately to severely active ulcerative colitis (UC). Among the four studies, two trials assessing etrolizumab as induction therapy met their primary endpoints of achieving patient remission; however, the two trials evaluating etrolizumab as maintenance therapy failed to meet their primary endpoints, primarily due to the lack of a significant difference in the proportion of patients achieving remission between those receiving subcutaneous etrolizumab and those receiving placebo.

Specifically, the results announced pertain to the following trials:

HIBISCUS I and II: Two identical, randomized, double-blind, double-dummy, placebo-controlled, multicenter Phase 3 clinical studies evaluated the efficacy (induction of remission) and safety of etrolizumab versus adalimumab and placebo in patients with moderately to severely active ulcerative colitis (UC) who were previously untreated with anti-tumor necrosis factor (anti-TNF) agents.

HICKORY: A double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of etrolizumab for induction and maintenance therapy in patients with moderately to severely active ulcerative colitis (UC) who have previously received anti-TNF therapy.

LAREL: A randomized, double-blind, placebo-controlled, multicenter Phase 3 clinical study to evaluate the efficacy (maintenance of remission) and safety of etrolizumab in patients with moderately to severely active ulcerative colitis (UC) who have not previously been treated with anti-TNF therapy.

In the HIBISCUS I induction study, the etrolizumab group met the primary endpoint. In the HIBISCUS II induction study, the etrolizumab group did not meet the primary endpoint. In the HICKORY study, etrolizumab met the primary endpoint during the induction phase but failed to meet the primary endpoint during the maintenance phase. In the LAUREL study, etrolizumab failed to meet its primary endpoint as maintenance therapy.

The safety profile of the drug was consistent with previous studies, and no significant safety concerns were identified in the four reported Phase 3 clinical trials. Roche stated that further analysis of data, including secondary endpoints, is underway, and additional data and details will be released in a timely manner.

Inflammatory bowel disease (IBD) is a group of chronic gastrointestinal disorders affecting nearly 7 million people worldwide. The two main types of IBD are ulcerative colitis (UC) and Crohn’s disease (CD). Approximately 80% of patients with IBD fail to achieve sustained remission, which can have long-term impacts on quality of life and leave many patients feeling nearly unable to control their daily activities. UC most commonly affects young adults aged 15–30 years, impacting their entire future life course. Up to one-quarter of patients with UC require colectomy—removal of part or all of the colon—within 10 years of diagnosis.

In response to this substantial market demand, Genentech initiated the largest clinical trial program for etrolizumab in inflammatory bowel disease (IBD) to date, enrolling participants from more than 40 countries worldwide. The program comprises eight randomized controlled and open-label trials, including head-to-head comparisons against the most commonly used current treatment regimens. In addition to the study whose results are being announced here, the program also includes:

GARDENIA: A randomized, multicenter, double-blind, double-dummy study to evaluate the efficacy (sustained remission) and safety of etrolizumab versus infliximab in patients with moderately to severely active ulcerative colitis.

COTTONWOOD: An open-label extension and safety monitoring study in patients with moderate to severe ulcerative colitis (UC) who had previously participated in Phase 2/3 studies of etrolizumab.

BERGAMOT: A randomized, double-blind, placebo-controlled, multicenter Phase 3 clinical study evaluating the efficacy and safety of etrolizumab as induction and maintenance therapy in patients with moderately to severely active Crohn’s disease (CD).

JUNIPER: An open-label extension and safety monitoring study in patients with moderately to severely active Crohn’s disease who previously participated in the Phase 3 BERGAMOT study of etrolizumab.

However, the results indicate that the Phase 3 clinical trial of etrolizumab clearly did not proceed as expected, paving a difficult path for this major pharmaceutical company and making it harder to compete with Takeda’s UC drug, Entyvio.

Etrolizumab is the first investigational dual-integrin antibody for inflammatory bowel disease (IBD), developed by Genentech through engineering of the FIB504 antibody to target the β7 subunit of the α4β7 and αEβ7 integrin heterodimers. By selectively inhibiting α4β7 and αEβ7, it controls immune cell trafficking into the intestine and their pro-inflammatory effects, thereby targeting IBD through two distinct mechanisms. According to data from a previous meta-analysis, etrolizumab demonstrated comparable efficacy to conventional therapies such as infliximab, with a lower incidence of adverse events.

According to EvaluatePharma’s analysis, Entyvio’s profits are projected to be slightly below $1 billion by 2026, while etrolizumab’s profits are expected to reach just under $891 million. The latest data may be reducing this valuation. Roche had originally planned to submit a marketing application for the drug this year, but this was not mentioned in the press release announcing the data. In addition, Genentech is developing other investigational drugs for inflammatory bowel disease (IBD), including an IL-22 fusion protein, which has currently entered Phase II clinical trials for IBD.

Reference Sources:

1、Hits, but mostly misses for Roche’s 4 late-stage trials of GI drug hopeful etrolizumab

2、Genentech Provides Update on Phase III Studies of Etrolizumab in People With Moderately to Severely Active Ulcerative Colitis