Horizon Scanning Technology Briefing. Alvimopan (Entrareg ) for opioid-induced bowel disfunction. National Horizon Scanning Centre.

Transcription

1 Horizon Scanning Technology Briefing National Horizon Scanning Centre Alvimopan (Entrareg ) for opioid-induced bowel disfunction August 2006 This technology briefing is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes.

2 Alvimopan (Entrareg ) for opioid-induced bowel dysfunction Target group Bowel dysfunction induced by opioid analgesics. Technology description Alvimopan (Entrareg, ADL ) is a peripheral opioid mu receptor antagonist in phase III development for the control of opioid-induced bowel dysfunction (OIBD). Opioid-induced bowel dysfunction (OIBD), also know as OBD, is a gastrointestinal condition characterised by (i) hard, dry stools, (ii) straining, (iii) incomplete evacuation, (iv) bloating, (v) abdominal distension, and (vi) increased gastric reflux. Alvimopan is administered orally 0.5 mg once or twice a day. Opioid analgesics (e.g. morphine and codeine) are used in patients with chronic cancer pain and for patients with moderate to severe non-malignant pain. Although opiates are effective for pain management, opioidinduced bowel dysfunction is a common and often debilitating side-effect. 1 Innovation and/or advantages Alvimopan is intended to block the negative effects of opioids on the gastrointestinal system without disrupting their analgesic function. Apart from laxatives, there is currently no specific treatment for OIBD, which can have a major impact on the quality of life of patients and their carers. Developer GlaxoSmithKline and Adolor Corporation. Purpose Diagnosis or identification of disease Prevention e.g. immunisation, public health programme Continuous therapy e.g. dialysis, life support Service delivery changes Investigation, assessment or staging of known disease Screening programme or tests to identify latent or early disease Patient management and pathways of care Susceptibility testing for identifying risk of disease Individual treatment e.g. drug, device, procedure, radiotherapy Rehabilitation Place of use Home care e.g. home dialysis Secondary care e.g. general, non-specialist hospital General public e.g. over the counter Community or residential care e.g. district nurses, physio Tertiary care e.g. highly specialist services or hospital Primary care e.g. used by GPs or practice nurses Emergency care e.g. paramedic services, trauma care Stage of development and availability in EU/UK Phase III clinical trials or Pre-registration in EU (drugs) equivalent Licence or CE mark application Licence or CE mark application in in UK/EU likely within 12 months UK/EU likely within 24 months Launch or use in UK/EU likely Established product, but this is a within 24 months new indication in development CE marked, but not yet launched or available in UK Launch or use in UK/EU likely within 12 months Aug

3 NHS or Government priority area Cancer Cardiovascular disease Children Diabetes Chronic conditions Mental health Older people Public health Renal disease Women s health None identified Relevant guidance None identified. Clinical need and burden of disease Published studies indicate that constipation occurs in 15-33% 2, 3, 4 of patients taking opioid analgesics. An expert opinion suggested this figure is closer to 4% for persistent constipation, half of these being severe. OIBD can have a major impact on quality of life for patients and their carers, and can lead to complications requiring hospitalisation (e.g. obstruction of the bowel). It may also interfere with drug absorption. Existing comparators and treatments Laxatives ineffective in some of patients. Tertiary opioid receptor antagonists such as naloxone, naltrexane and nalmefene. These reduce primary symptoms, but can also reverse analgesia and provoke opioid withdrawal symptoms in some patients, limiting their clinical use. 5 Efficacy and safety Trial name or /013 13C304 code Sponsor GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline Status Ongoing Ongoing Abstract 6 Location North America and North America and North America Europe Europe Design Phase III, randomised, double blind, placebocontrolled Phase III randomised, double blind, placebocontrolled Participants in trial number, description, trial schedule e.g. placebo or comparator Follow-up Primary outcome Secondary outcomes n=805. Adults with persistent noncancer pain. Alvimopan 0.5 mg vs. placebo twice daily for 12 months. 1 year Adverse clinical events, tolerability Quality of life, pharmacokinetics n=491. Adults with persistent non-cancer pain. Alvimopan 0.5 mg either once or twice daily, vs. placebo for 12 weeks. Spontaneous bowel movement (BM) frequency BM/related abdominal symptoms; BM frequency; changes in constipation-specific quality of life; adverse events; changes in pain intensity scores; opioid use. Phase III randomised, double blind, placebo-controlled n=168. OIBD treated with opioids 1 month. Pain or opioid addiction. 0.5 mg or 1.0 mg Alvimopan vs. placebo once daily for 21 days. 1 BM < 8 hours after each dose Aug

4 Key results Expected reporting date Major adverse effects April 2007 End 2006 Early BM significantly greater compared to placebo: 54% for 1 mg group (p<0.001 vs. placebo), 43% for 0.5 mg group (p<0.001 vs. placebo), and 29% for placebo. Opioid consumption and pain intensity scores unchanged. None Estimated cost and cost impact The estimated cost of the product is not publicly available. Potential or intended impact speculative Patients Reduced morbidity Quicker or more accurate diagnosis Reduced mortality or increased survival Earlier identification of disease Improved quality of life for patients and/or carers Changed pathway of care or outcome Services Increased use e.g. length of stay, Service reorganisation required out-patient visits Decreased use e.g. shorter length of stay, reduced referrals Staff or training required Costs Increased unit cost compared to alternative Increased costs: more patients receiving treatment Increased costs: capital investment needed Savings: reduced need for primary and secondary care (resulting from better management of the condition) References 1 Quigley C. The role of opioids in cancer pain. BMJ 2005; 331: Moore A et al. Prevalence of opioid adverse events in chronic non-malignant pain: systematic review of randomised trials of oral opioids. Arthritis Research and Therapy 2005; 7(5): R Meuser T et al. Symptoms during cancer pain treatment following WHO guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology. Pain 2001; 93(3): Grond S et al. Prevalence and pattern of symptoms in patients with cancer pain: a prospective evaluation of 1635 cancer patients referred to a pain clinic. J Pain Symptom Management 1994, 9: Robinson CB et al. Clin J Oncol Nurs 2000; 4: Pappagallo M. Incidence, prevalence, and management of opioid bowel dysfunction. Am J Surgery 2001; 182: Paulson DM, et al. Alvimopan: an oral, peripherally-acting, mu-opioid receptor antagonist for the treatment of opioid-induced bowel dysfunction a 21-day treatment-randomised clinical trial. J Pain 2005; 6(3): Aug

5 The is funded by the Research and Development Division of the Department of Health, England The, Department of Public Health and Epidemiology University of Birmingham, Edgbaston, Birmingham, B15 2TT, England Tel: +44 (0) Fax +44 (0) Aug