NICE publishes positive final guidance on Entyvio (vedolizumab) for selected use in adults with moderately to severely active Crohn's Disease

The National Institute for Health and Care Excellence (NICE) has published final Technology Appraisal Guidance (TAG) for Entyvio (vedolizumab), the first gut- selective treatment for Crohn's Disease (CD).¹ NICE recommends vedolizumab as an option for use on the NHS for adults with moderately to severely active CD who have either failed,* or were intolerant or contraindicated to, an anti-TNF (tumour necrosis factor-alpha antagonist). NICE recognises vedolizumab as an innovative, cost-effective treatment that provides remission from symptoms.¹ The annual UK cost per CD patient in relapse is estimated to be £10,513.⁴

Vedolizumab is a 30-minute intravenous infusion given every eight weeks at a fixed dose of 300mg.⁵ It works selectively in the gut to help block the entry of white blood cells,⁵ reducing inflammation and associated symptoms, such as malnutrition, weight loss, urgent and frequent diarrhoea and rectal bleeding.⁶

These distressing symptoms can leave people housebound⁷ and have a wide-ranging and devastating impact on mental health, relationships and employment.¹

Crohn's and Colitis UK, welcomes this recommendation and highlights that vedolizumab could make a fundamental difference in enabling some people with CD to get on with their lives.³

Dr Jeremy Sanderson, Consultant Gastroenterologist, commented "Getting patients into remission and keeping them there long-term is the primary goal of treatment. For our patients, active disease has a huge negative impact across all aspects of daily life. Vedolizumab is an effective and much needed additional treatment option for patients with Crohn's Disease."

As part of its decision, NICE recognises that vedolizumab works differently to existing treatments for CD and considered this to be an innovation;¹ selectively targeting the immune system in the gut.⁵ Importantly, clinical experts consulted by NICE felt that vedolizumab has a more favourable adverse-event profile than existing biological treatments because of this 'gut-specific' effect and fewer systemic side effects.¹

The key evidence to support vedolizumab use in the treatment of moderately to severely active CD comes from clinical data submitted from the GEMINI II and GEMINI III studies;¹ part of the Phase III clinical trial programme evaluating the efficacy and safety of vedolizumab in both CD and Ulcerative Colitis (UC) patients.⁵

Efficacy - the NICE guidance states that in the induction phase of the GEMINI II study, clinical remission was significantly higher in patients who received vedolizumab than placebo at week 6 (14.5% and 6.8% respectively, p=0.02).1† A sub-group analysis of the data showed that of those patients who had failed one or more anti-TNF therapy, 10.5% and 16.0% responded to vedolizumab at week 6 and 10 respectively, compared to placebo (4.3% and 8.6% respectively).1‡ In the maintenance phase, clinical remission at week 52 was significantly higher in patients who received vedolizumab compared to placebo (treatment difference: 17.4% in patients receiving vedolizumab every 8 weeks, p=0.0007).1 A sub-group analysis of the data showed that of those patients who had failed one or more anti-TNF, 28.0% were in remission at week 52 compared to 12.8% on baseline therapies and placebo (treatment difference: 15.2%).¹‡

A further study with a similar patient population (GEMINI III) highlighted that there was no statistically significant difference in clinical remission between patients treated with vedolizumab and placebo at week 6.1 Analysis of the secondary outcomes of the study showed that, 26.6% of patients treated with vedolizumab were in remission at 10 weeks compared to 12.1% on baseline therapies and placebo (p=0.001).⁸‡§

Safety - the frequency of adverse events in the GEMINI II and GEMINI III studies with vedolizumab was similar to placebo (87% and 82% respectively), with the most common adverse event being exacerbation of CD (20.1% for vedolizumab and 21.6% for placebo).¹ Serious adverse events were more frequent in patients treated with vedolizumab than placebo (24.4% and 15.3% respectively).¹

Adam Zaeske, Managing Director of Takeda UK and Ireland, commented "We are pleased to receive final NICE guidance for vedolizumab in CD as this brings patients a step closer to a much needed additional treatment option. Vedolizumab has been recommended by NICE and accepted by SMC for restricted use in CD, and across its full licenced indication in UC, within 18 months of EMA licence, which demonstrates both the treatment innovation of vedolizumab and our commitment to addressing unmet patient needs."

Following today's publication, clinical commissioning groups have an obligation to ensure that vedolizumab is made available to appropriate patients within 90 days and no later than 24 November 2015.¹ This guidance is contingent upon Takeda UK providing vedolizumab to the NHS within the terms of an agreed patient access scheme.¹

Today's decision is the second positive NICE ruling for vedolizumab - on 5 June 2015, NICE published positive final guidance on vedolizumab for adults with moderately to severely active UC across its full licenced indication.⁹

About Crohn's Disease

Crohn's Disease (CD) is a life-long condition characterised by chronic inflammation of any part of the digestive system, but most commonly occurring in the last section of the small intestine (ileum) or the large intestine (colon).² Affecting around 115,000 people,² the UK has one of the highest incidences of CD in Europe.¹⁰ It is a relapsing condition, usually diagnosed in the late teens or early twenties and often leaves young adults dealing with unpredictable, debilitating symptoms when they are studying, finding their first job and establishing their adult lives.¹¹

The inflammation in CD may lead to narrowing of the bowel resulting in abdominal pain caused by partial blockage. Severe cases may lead to life-threatening complications such as complete blockage or perforation of the bowel.¹¹

The treatment of CD has significant cost implications due to the rising incidence of the condition, young age of onset and its incurable nature. The 2010 National Inflammatory Bowel Disease Audit estimated the cost of UC and CD to the NHS to be more than £1 billion. A recent study calculated the average annual cost for any patient with CD in the UK to be £6,156, the annual cost per CD patient in remission to be £1,799 and the annual cost per CD patient in relapse to be £10,513.⁴

About VEDOLIZUMAB

Vedolizumab is licensed for the treatment of adults (≥18 years old) with moderately to severely active Ulcerative Colitis (UC) and adults (≥18 years old) with moderately to severely active Crohn's Disease (CD) who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumour necrosis factor-alpha antagonist (anti-TNF).⁵

Vedolizumab works by binding exclusively to the α4β7 integrin, which is expressed on a sub-group of lymphocytes (a type of white blood cell) that bind to the MAdCAM-1 receptor, expressed preferentially in the gut. By blocking the α4β7 integrin, vedolizumab selectively reduces the influx of inflammatory cells to the gut.⁵ In clinical trials in adults with moderately to severely active UC and CD, vedolizumab was generally well tolerated and showed statistically significantly better efficacy compared to placebo across a range of endpoints.^12,13

The safety and efficacy of vedolizumab was evaluated in the GEMINI Studies, the largest Phase 3 clinical trial programme to date evaluating both UC and CD patients in parallel.^{8,12,13,14,15} In UC studies, vedolizumab has been shown to induce clinical response, remission and mucosal healing in patients with no prior anti- TNF exposure, as well as in those who have not responded or become intolerant to anti-TNF therapy.¹² In CD studies, vedolizumab has been shown to induce clinical remission and to produce a clinical response and a corticosteroid-free clinical remission (at week 52) in patients with no prior anti-TNF exposure, as well as in those who have not responded or become intolerant to prior anti-TNF therapy.¹³ The most common side- effects were CD exacerbations,¹³ nasopharyngitis (common cold), headache, arthralgia (joint pain), upper respiratory tract infection, fatigue, pyrexia (fever), nausea, and cough.⁵ As with other biologic treatments, there is an increased risk of infection and patients should be issued with a Patient Alert Card.⁵