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National Horizon Scanning Centre

Amibegron (SR–58611) for depression

April 2008

This technology summary 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.

The National Horizon Scanning Centre Research Programme is part of the National Institute for Health Research

April 2008 National Horizon Scanning Centre News on emerging technologies in healthcare

Amibegron (SR–58611) for depression

Target group • Major depressive disorder (MDD).

Technology description Amibegron is a selective beta 3-adrenoceptor, which stimulates neuronal activity in a specific area of the prefrontal cortex. Amibegron is an oral formulation administered at 175mg or 350mg twice daily.

Innovation and/or advantages Amibegron is the first in a new class of agents. It is anticipated that it will have less toxicity than current treatments.

Developer -Aventis.

Availability, launch or marketing dates, and licensing plans: In phase III clinical trials.

NHS or Government priority area: This topics relates to the National service framework for mental health: modern standards and service models. 19991.

Relevant guidance • NICE technology appraisal. Depression and anxiety - Computerised cognitive behaviour therapy for depression and anxiety. 20062. • NICE clinical guideline in development. Depression - primary and secondary care: The treatment and management of depression in primary and secondary care. Expected June 20093. • NICE clinical guideline in development. Depression - chronic health problems: The treatment of depression in people with chronic physical health problems. Expected June 20094. • NICE clinical guideline. Depression: management of depression in primary and secondary care. 20045.

Clinical need and burden of disease Depression is the second most common cause of disability worldwide. In the UK, depression affects between 5% and 10% of individuals and is the third most common reason for consultation in general practice. Depression is associated with a marked reduction in functional capacity and quality of life. Whilst depressive disorders are common, they may go unrecognised which is associated with poor treatment outcome6,7.

Existing comparators and treatments Combining drug therapy with psychological treatments, such as cognitive behaviour therapy (CBT), is usually the most effective option for severe depression.

Current antidepressant drug classes for major depression include: • e.g. , and • Heterocyclic antidepressants e.g. and • SSRIs e.g. , , and 2 April 2008 National Horizon Scanning Centre News on emerging technologies in healthcare

• Monoamine oxidase inhibitors e.g. and • Other newer drugs e.g. , , and .

Efficacy and safety

Trial code NCT00385307 NCT00319709 (ZEPHIR)9; NCT00252356 (SIRIUS)8; MDD; elderly, MDD; amibegron vs (ORION)10; MDD; amibegron vs paroxetine; placebo; phase III. amibegron vs phase III. escitalopram; phase III. Sponsor Sanofi-Aventis Sanofi-Aventis Sanofi-Aventis Status Completed Completed Completed Location USA Europe USA, Canada Design Randomised, double- Randomised, double-blind, Randomised, double- blind, controlled. placebo controlled. blind, controlled. Participants in n=660; adults 18 to 65 n=280; adults >65 years with n=450; adults >18 years; trial years; MDD; previously MDD. Randomised to MDD. Randomised to untreated. Randomised to amibegron 700mg twice- amibegron 350mg twice amibegron 175mg, 350mg daily or placebo. daily or escitalopram 10 twice-daily or paroxetine mg daily. 1-week placebo, 10mg daily. single-blind period. 8- week double blind period. Optional 18-week double- blind extension. 1-week safety follow-up period. Follow-up 8 weeks 8 weeks 18 weeks Primary Depressive rating scale at Safety and efficacy; day 56 Safety and efficacy; outcome 8 weeks. of treatment with Hamilton HAM-D. depression rating scale (HAM-D). Secondary Safety. Clinical global impression CGI severity score; outcomes (CGI) severity score; MADRS. Montgomery-Åsberg Depression Rating Scale (MADRS). Expected Study started September Study started April 2006. Study started September reporting date 2006. Results expected Reporting date unknown. 2005. Reporting date during 2008. unknown.

Trial code NCT00252330 NCT00345098 NCT00432614 (PHOENIX)11; MDD; (CALYPSO)12; MDD; (ALBERIO)13; MDD; amibegron vs prevention of relapse; phase escitalopram; phase III. escitalopram; phase III. III. Sponsor Sanofi-Aventis Sanofi-Aventis Sanofi-Aventis Status Completed Ongoing Ongoing Location USA, Canada. South America, Europe, Europe, Asia, North Russia, South Africa. Africa. Design Randomised, double-blind, Randomised, double-blind, Randomised, double- controlled. placebo controlled. blind, placebo controlled. Participants n=450; adults >18 years; n=800; adults; MDD. n=500; adults 18 to 65 in trial MDD. Randomised to: Patients demonstrating years; MDD on amibegron 350mg twice improvement in depressive escitalopram 10mg per daily or escitalopram symptoms after 12-week day. Randomised to 10mg daily. 1-week open-label treatment period amibegron 350mg twice- placebo, single-blind using amibegron. daily or placebo. period. 8-week double Randomised to amibegron 3 April 2008 National Horizon Scanning Centre News on emerging technologies in healthcare

blind period. Optional 18- 350mg twice daily or week double-blind placebo. extension. 1-week safety follow-up period. Follow-up 18 weeks 52 weeks 8 weeks Primary Safety and efficacy; HAM- Safety and efficacy; relapse Safety and efficacy; outcome D. (in days) in randomised HAM-D. study assessed using MADRS. Secondary CGI severity score; CGI severity score; HAM-D. CGI severity score; speed outcomes MADRS. of response. Expected Study started September Study started May 2006. Study started February reporting date 2005. Reporting date Reporting date unknown. 2007. Reporting date unknown. unknown.

Estimated cost and cost impact The cost of amibegron has not yet been determined. Costs for other drugs for depression are:

Drug Dose per day Cost per montha Amitriptyline 75 - 150mg £13 - £26 Escitalopram 20 - 40mg £96 - £162 Moclobemide 150 - 600mg £60 - £180 Mirtazapine 15 - 45mg £69 - £207

Potential or intended impact – speculative

Patients Reduced morbidity Reduced mortality or increased ; Improved quality of life for survival patients and/or carers Quicker, earlier or more accurate Other: None identified diagnosis or identification of disease

Services Increased use Service reorganisation required Staff or training required

Decreased use Other: ; None identified

Costs Increased unit cost compared to Increased costs: more patients Increased costs: capital alternative coming for treatment investment needed ; New costs: May be a more Savings: Other: expensive option than some current drug options.

References

1 National service framework for mental health: modern standards and service models. Department of Health. HSC 1999/223. September 1999. 2 National Institute for Health and Clinical Excellence. Depression and anxiety - Computerised cognitive behaviour therapy for depression and anxiety. Technology appraisal TA97. February 2006. a Costs from British National Formulary No. 55, March 2008. 4 April 2008 National Horizon Scanning Centre News on emerging technologies in healthcare

3 National Institute for Health and Clinical Excellence. Depression - primary and secondary care: The treatment and management of depression in primary and secondary care (partial update of CG23). Technology appraisal in development. Expected June 2009. 4 National Institute for Health and Clinical Excellence. Depression - chronic health problems: The treatment of depression in people with chronic physical health problems (partial update of CG23). Technology appraisal in development. Expected June 2009. 5 National Institute for Health and Clinical Excellence. Depression: management of depression in primary and secondary care. Clinical guideline CG23. December 2004 (Expected review December 2008). 6 NHS Centre for Reviews and Dissemination. Effective Health Care: Improving the recognition and management of depression in primary care. 2002;7(5). Available at: http://www.york.ac.uk/inst/crd/ehcb.htm (Accessed 4/3/08). 7 EMedicine. Depression. Available at: http://www.emedicine.com/rc/rc/i7/depression.htm (Accessed 4/3/08). 8 ClinicalTrials. Efficacy and safety of SR58611A in patients with major depressive disorder. Available at: http://clinicaltrials.gov/ct2/show/NCT00385307?term=NCT00385307&rank=1 (Accessed 4/3/08). 9 ClinicalTrials. Efficacy and safety of SR58611A in patients with major depressive disorder. Available at: http://clinicaltrials.gov/ct2/show/NCT00319709?term=NCT00319709&rank=1 (Accessed 4/3/08). 10 ClinicalTrials. Efficacy and safety of SR58611A in patients with major depressive disorder. Available at: http://clinicaltrials.gov/ct2/show/NCT00252356?term=NCT00252356&rank=1 (Accessed 4/3/08). 11 ClinicalTrials. Efficacy and safety of SR58611A in patients with major depressive disorder. Available at: http://clinicaltrials.gov/ct2/show/NCT00252330?term=nct00252330&rank=1 (Accessed 4/3/08). 12 ClinicalTrials. Efficacy and safety of SR58611A in patients with major depressive disorder who have relapsed. Available at: http://clinicaltrials.gov/ct2/show/NCT00345098?term=NCT00345098&rank=1 (Accessed 4/3/08). 13 ClinicalTrials. Efficacy and safety of SR58611A co-administered with escitalopram in patients with major depressive disorder. Available at: http://clinicaltrials.gov/ct2/show/NCT00432614? term=NCT00432614 &rank=1 (Accessed 4/3/08).

The National Institute for Health Research National Horizon Scanning Centre Research Programme is funded by the Department of Health. The views expressed in this publication are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health

The National Horizon Scanning Centre, Department of Public Health and Epidemiology University of Birmingham, Edgbaston, Birmingham, B15 2TT, England Tel: +44 (0)121 414 7831 Fax +44 (0)121 414 2269 www.pcpoh.bham.ac.uk/publichealth/horizon

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