Genentech's Investigational UC Treatment Posts Mixed Results in Late-Stage Studies

A Genentech investigational ulcerative colitis treatment etrolizumab posted mixed results in its late-stage study program in patients who have moderate or severe active forms of the disease.

On Sunday, South San Francisco-based Genentech announced that mixed results were seen in studies evaluating etrolizumab as an induction therapy, and both studies evaluating etrolizumab as a maintenance therapy failed to meet their primary endpoints. Genentech said etrolizumab demonstrated no significant difference in the proportion of people achieving remission with subcutaneous etrolizumab versus placebo.

Etrolizumab is Genentech’s first investigational dual anti-integrin studied in inflammatory bowel diseases (IBD). It is designed to target IBD on two fronts by selectively inhibiting α4β7 and αEβ7 to control both trafficking of immune cells into the gut and their inflammatory effects on the gut lining.

In the Phase III HIBISCUS I induction study, which assessed patients people without prior anti-tumor necrosis factor (anti-TNF) treatment, etrolizumab met the primary endpoint, the company said. However, in the HIBISCUS II induction study, which also included people without prior anti-TNF treatment, etrolizumab did not meet its primary endpoint. In the HICKORY study, in people with prior anti-TNF treatment, etrolizumab met the primary endpoint at induction but not at maintenance and in the LAUREL maintenance study in people without prior anti-TNF treatment, etrolizumab failed to meet its primary endpoint.

The safety profile of etrolizumab was consistent with previous studies and no major safety issues were identified in the four Phase III clinical trials reported to date, the company said.

Levi Garraway, chief medical officer and head of Global Product Development for Genentech, a Roche company, said he was disappointed in the results from the study due to the fact that people with ulcerative colitis need new treatment options. Ulcerative colitis is one of two of the main forms of irritable bowel disease. Ulcerative colitis typically affects the colon and rectum. Patients can experience unpredictable symptoms that include abdominal pain and cramping, frequent and urgent bowel movements, diarrhea, leakage, rectal bleeding, weight loss, energy loss and fatigue. Ulcerative colitis is most commonly diagnosed in young people aged 15 to 30 years, affecting them over the course of their entire future lives. Up to a quarter of people with ulcerative colitis will require a colectomy within 10 years of diagnosis, in which all or part of the colon is removed.

“We are fully analyzing these data to learn more about how we might address the needs of people with this devastating disease. These studies were part of the largest clinical trial program ever undertaken in inflammatory bowel diseases, and we thank all the patients, investigators and healthcare professionals for their participation,” Garraway said in a statement.

Genentech intends to analyze the data from the four studies, including secondary endpoints. Full data from these studies will be presented at a future medical meeting.

As the company analyzes the data, Genentech continues to study etrolizumab as an investigational induction and maintenance treatment in people with moderately to severely active Crohn’s disease with and without prior anti-TNF treatment.