Roche Gut Disease Drug Produces Mixed Results in Late-Stage Trials

Results from four studies within a major Roche-run clinical trials program of an investigational gut disease drug have muddled the antibody’s path forward after its performance proved mixed.

The company has been studying etrolizumab, an antibody designed to block two members of a family of proteins called integrins, as a potential treatment for the two most common inflammatory bowel diseases. The aim of the dual anti-integrin, which patients administer monthly via an injection, is to stop white blood cells from entering the gut and reduce the inflammatory effects caused by the immune overreaction that characterizes IBD.

Ulcerative colitis (UC) is one of the two main types of IBD, a group of chronic gastrointestinal (GI) disorders. UC affects primarily the colon while the other primary form of IBD, Crohn’s disease, affects the entire GI tract. According to the Centers for Disease Control, 3 million US adults reported being diagnosed with UC or Crohn’s disease in 2015.

Without breaking out the numbers, Roche reported preliminary findings from four trials that evaluated etrolizumab for UC patients. The company said the drug met its main goal in HIBISCUS I, one of two studies primarily measuring the antibody’s ability to induce disease remission against a placebo after 10 weeks. However, the drug missed that goal in an identically designed trial, HIBISCUS II. Those trials tested etrolizumab, the AbbVie (NYSE: [[ticker:ABBV]]) drug adalimumab (Humira), and a placebo in patients with moderately to severely active forms of the disorder who had not undergone prior treatment with another class of gut disease drugs, biologics that work by blocking a protein called tumor necrosis factor (TNF).

In another trial, LAUREL, which also enrolled only patients who had not undergone anti-TNF treatment, the drug failed to meet its main goal as a maintenance therapy. In a fourth, HICKORY, which enrolled patients who had previously received anti-TNF treatment, etrolizumab succeeded as an induction therapy—but failed at maintenance.

Although in a given year about half of people with UC are in remission, the disease is a chronic one punctuated by the reoccurrence of symptoms, called flares. Longer stretches in remission make flares less likely, according to the Crohn’s and Colitis Foundations of America.

The trials results reported Monday were part of what Roche describes as the largest clinical trial program in inflammatory bowel diseases to date, with six Phase 3 studies and two open-label extensions collectively involving more than 3,100 patients across 40-plus countries. The company said no safety issues arose in the four trials from which it has reported results.

Levi Garraway, Roche’s chief medical officer and global product development head, said in a prepared statement that the company continues to study the data, including how the drug measured up against secondary goals, and that it plans to submit the analyses for presentation at future medical meetings.

Takeda Pharmaceutical (NYSE: [[ticker:TAK]]) already markets an anti-integrin antibody for UC and for Crohn’s disease, vedolizumab (Entyvio). Approved in 2014, the blockbuster treatment—designed to block one protein rather than two—is administered intravenously, a procedure that takes about 30 minutes. Takeda has developed an injectable version, which the FDA rejected last December but European regulators OK’d in May. In the company’s most recent fiscal year, which ended in March, the drug was the company’s top seller, bringing in about $3.2 billion. That was 29 percent more than the year prior. In this fiscal year, Takeda estimates a 23.8 percent year-over-year sales increase, which would put revenue from the drug at more than $4 billion.

Roche’s etrolizumab remains under evaluation in a Phase 3 study for more than 1,100 Crohn’s disease patients, a trial anticipated to finish in 2021.