How etrolizumab works
It is a monoclonal antibody — a protein that has been designed to target and block a specific type of protein. The compound stops two proteins involved in the immune response, alpha4beta7 (α4β7) and alphaEbeta7 (αEβ7), from working.
IBD is caused by the immune system attacking the cells of the digestive system, leading to inflammation (swelling) and possible blockage or ulcers. The immune system recruits white blood cells into the gut from the blood stream, and these cells build and damage gut tissue.
α4β7 and αEβ7 are two of the proteins involved in moving white blood cells from the bloodstream into the gut and keeping them there. Bt inhibiting these proteins, etrolizumab aims to reduce inflammation.
Etrolizumab in clinical trials
It has successfully been tested for the treatment of moderate to severe ulcerative colitis in a Phase 1 (NCT00694980) and a Phase 2 (NCT01336465) clinical trial, results of which were published, respectively, in the scientific journals Gut and The Lancet. These studies show that etrolizumab treatment was well-tolerated, and resulted in an improvement in the rate of clinical remission in UC patients compared to placebo.
It is currently in a Phase 3 clinical trial as part of Genentech’s Etro Studies program, assessing its safety and efficacy in both UC and Crohn’s. During this trial, etrolizumab will be compared to other currently the U.S. Food and Drug Administration (FDA)-approved drugs, namely Remicade (infliximab) and Humira (adalimumab), and to placebo. There are five planned trials for patients with UC, and two for those with CD, to be carried out in the U.S., as well as one non-U.S. based trial in UC patients. All these studies are currently recruiting participants.
Hibiscus I (NCT02163759) aims to assess whether etrolizumab can induce clinical remission in UC patients, and and Hibiscus II (NCT02171429) to compare its effectiveness with Humira. Genentech aims to recruit 350 participants for each study.
The Laurel (NCT02165215) trial will assess whether etrolizumab can successfully maintain clinical remission in patients with UC for 52 weeks compared to a placebo (following a 10-week induction of remission with etrolizumab). Patients must not have tried a previous anti-TNF treatment, and have failed at or were unable to tolerate immunosuppressant and/or corticosteroid treatment, to take part in this trial.
The Hickory (NCT02100696) trial will assess whether etrolizumab can successfully induce and maintain clinical remission in ulcerative colitis patients who are intolerant to or did not respond to other anti-TNF treatments.
The Cottonwood (NCT02118584) trial will enroll UC patients who previously took part in an etrolizumab study to assess its long-term safety and efficacy (104 weeks).
The Gardenia (NCT02136069) trial will be carried out at multiple centers outside the U.S., and will compare the efficacy and safety of etrolizumab plus Remicade in patients with UC.
The Bergamot (NCT02394028) trial will assess two doses of etrolizumab (210 mg and 105 mg) compared to a placebo in patients with moderate to severe Crohn’s who either never used ant anti-TNF or failed to respond well to this treatment. The trial aims to determine whether etrolizumab can successfully induce remission after 14 weeks compared to placebo, then determine whether it can maintain remission for a 60-week maintenance phase.
Patients who successfully complete the Bergamot trial can choose to enroll in the Juniper trial (NCT02403323), which is an open-label study assessing the long-term safety and efficacy of etrolizumab in CD patients.
Etrolizumab has not yet been approved by the FDA for the treatment of IBD.
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