Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced data from two ongoing phase III trials evaluating etrolizumab in patients with inflammatory bowel disease (IBD). Results from the BERGAMOT and HICKORY trials indicated that patients treated with etrolizumab showed an improvement in both patient reported symptoms and endoscopic assessment of inflammation.1,2 Findings were presented at the 25th United European Gastroenterology Week (UEGW) congress, 28 October – 1 November 2017, in Barcelona, Spain.
Data from an exploratory cohort (Cohort 1) of the phase III BERGAMOT study evaluating the safety and efficacy of etrolizumab (105 mg subcutaneous [SC] every 4 weeks [q4w]) or etrolizumab high dose (210 mg SC at weeks 0, 2, 4, 8, and 12) versus placebo in previously treated patients with moderate-to-severe Crohn’s disease, suggest an early and persistent symptomatic remission.1 Key data include:
This study utilised assessment of endoscopic videos by an independent panel of expert central readers blinded to patient’s treatment assignment.1 Approximately 75% of the patients in this cohort had previous failure of aTNF therapy.1 These results will help refine and finalise the endpoints used for the pivotal cohort (Cohort 3) of the BERGAMOT trial.
In patients with moderate-to-severe UC and prior aTNF failure, updated results from the open label induction cohort (130 patients treated with etrolizumab 105 mg q4w for 14 weeks) within the phase III HICKORY study were also presented, suggesting that treatment with etrolizumab resulted in a clinically meaningful improvement as observed in endoscopic improvement as well as clinical response and remission.2
Both studies found that etrolizumab was well tolerated, with a frequency of adverse events comparable with placebo.1,2
“Management of inflammatory bowel disease is challenging, as only around half of patients will achieve a response or remission with current therapies,” said Sandra Horning, M.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We are encouraged by these early data across both ulcerative colitis and Crohn’s disease, which highlight the potential of etrolizumab as a much needed new treatment option for these patients.”
BERGAMOT and HICKORY are part of a global phase III clinical development programme for etrolizumab in patients with UC and Crohn's disease, which aims to assess important clinical questions in IBD.3,4 It is the first clinical development programme to address a number of key questions in phase III studies:
The etrolizumab programme will enrol more than 3,400 patients across eight pivotal phase III studies, for UC and Crohn’s disease.
BERGAMOT is a phase III multi-centre, double-blind, randomised, placebo-controlled study evaluating the efficacy and safety of etrolizumab during induction and maintenance in patients with moderate-to-severe Crohn’s disease who have been previously treated with immunosuppressants, corticosteroids, and/or anti-tumour necrosis factor (aTNF) inhibitors. The study was designed with three sequential induction cohorts and a single maintenance cohort;
Patients in the etrolizumab arms of any of the induction cohorts who are responders at week 14 are re-randomised 1:1 to placebo or etrolizumab (105 mg SC q4w) for a maintenance phase of ≥ 52 weeks.
HICKORY is an ongoing phase III, multi-centre, double-blind, placebo-controlled study evaluating the safety, efficacy, and tolerability of etrolizumab during induction (week 14) and maintenance of remission (week 66) compared with placebo in patients with moderate-to-severe UC who have had a previous failure of aTNF therapy. Results from the open label induction cohort (n=130) were presented at UEGW. In the pivotal induction cohort, patients (n=670) will be randomised in a 4:1 ratio to receive either etrolizumab (105mg SC q4w) or placebo in a 14-week double-blind induction phase.
Patients who are clinical responders at week 14 from both cohorts will be randomised in a 1:1 ratio to receive either etrolizumab or placebo for a 52-week double-blind maintenance phase (from weeks 14 to 66).
Etrolizumab is an investigational dual action anti-integrin antibody designed to selectively control disease in the gut of patients with moderate-to-severe inflammatory bowel disease (UC or Crohn’s disease).7 Etrolizumab is thought to work by selectively targeting and attaching to a specific part (β7 subunit) of two key proteins (α4β7 and αEβ7 integrins) found on cells that play a key role in inflammation in IBD.7,8 With this dual mechanism of action etrolizumab has been designed with the objective of preventing inflammatory cells from entering and being retained in the gut.7,8 Etrolizumab can be self-administered once per month via the subcutaneous route, which means the drug is injected under the skin (tissue layer between the skin and muscle).9,10
Roche and Genentech have launched an extensive phase III clinical development programme, assessing the efficacy and safety of etrolizumab in patients with UC and Crohn's disease,3,4 which aims to address significant clinical unmet needs in the treatment of these diseases.
Ulcerative colitis:
Crohn’s:
IBD describes a group of diseases that involve chronic inflammation of the digestive tract with UC and Crohn’s being the two main types.11 UC is largely limited to the colon or large intestine and is characterised by a continuous pattern of ulcerations to the mucosal layer of the gut.12 Crohn’s disease can affect any part of the digestive tract from the mouth to the anus and it is characterised by inflammation that spans the intestinal wall and by skip lesions, which are intermittent areas of inflammation with healthy tissue present in between.12 In a healthy person the immune system usually attacks and kills foreign invaders, such as bacteria, viruses, and other microorganisms.12,13 However, in people with IBD, the immune system mounts an inappropriate response in the intestinal tract, resulting in prolonged inflammation.12,13
IBD is most common in developed countries, with approximately 3.6 million people in the United States and Europe living with the disease (1.4 million and 2.2 million, respectively)14 and the disease has an increased rate of diagnosis in adults between 15 and 35 years old.12 Despite patients with IBD being expected to have a normal life expectancy, a patient’s quality of life can be significantly compromised.15
Leveraging an established heritage of immunology, innovation, and personalised healthcare, Roche GastroImmunology™ is dedicated to following the science to improve patients’ lives.
Roche GastroImmunology™ is committed to
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The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2016 employed more than 94,000 people worldwide. In 2016, Roche invested CHF 9.9 billion in R&D and posted sales of CHF 50.6 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.
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