National Horizon Scanning Centre

Saredutant (SR-48968) for depression and anxiety

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

Saredutant (SR-48968) for depression and anxiety

Target group • Major depressive disorder (MDD) • Generalised anxiety disorder (GAD)

Technology description Saredutant is an oral treatment designed to block effects of the G protein couple receptor (GPCR) neurokinin-2 (NK-2). NK-2 is one of three tachykinin receptors. It binds to and induces production of a chemical called inositol triphosphate, which is found in elevated levels in patients suffering from depression. Saredutant is administered at 30mg or 100mg once-daily.

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

Developer Sanofi-Aventis.

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

NHS or Government priority area: This topics relates to the National service framework for mental health: modern standards and service models (1999)1.

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. • NICE clinical guideline. Anxiety: management of anxiety (panic disorder, with or without agoraphobia, and generalised anxiety disorder) in adults in primary, secondary and community care. 20046.

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 outcome7.

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Anxiety is a complex feeling of apprehension, fear, and worry often accompanied by pulmonary, cardiac, and other physical sensations. It is a ubiquitous condition that varies from the physiologic to the pathologic in its presentation. When pathologic, it can exist as a primary disorder, or it can be associated with medical illness, neurologic syndromes, or other primary psychiatric illnesses such as depression8. It is not clear whether anxiety leads to depression or whether depression causes anxiety9.

Existing comparators and treatments Combining 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 • Monoamine oxidase inhibitors e.g. and • Other newer e.g. , , and .

The treatment of GAD can involve: • Psychological therapy e.g. CBT • e.g. • Antidepressants e.g. SSRIs and venlafaxine •

Efficacy and safety

Trial code NCT0025611310; NCT0025061411; NCT0042926012; NCT0062955113; MDD; saredutant MDD; saredutant vs MDD; abrupt MDD; saredutant vs paroxetine; paroxetine; phase discontinuation of with paroxetine; phase III. III. saredutant; phase III. phase III. Sponsor Sanofi-Aventis Sanofi-Aventis Sanofi-Aventis Sanofi-Aventis Status Completed Completed Completed Recruiting Location France USA USA USA, South America, Europe, South Africa. Design Randomised, Randomised, Randomised, Randomised, double-blind, double-blind, double-blind, double-blind, controlled. controlled. placebo-controlled. placebo-controlled. Participants n=450; adults 18 to n=450; adults 18 to n=110; adults >18 n=820; adults 18 to in trial 64 years; MDD. 64 years; MDD. years; MDD. 65 years; MDD. Randomised to Randomised to Randomised to Randomised to saredutant 100mg saredutant 100mg or saredutant 100mg or saredutant 100mg or paroxetine. 1 paroxetine. 1 week placebo for 8 weeks or 30mg in week placebo, placebo, single- followed by abrupt combination with single-blind period, blind period, 8 week discontinuation of paroxetine 20mg vs 8 week double- double-blind period, treatment over 1 placebo and blind period, 44 44 week double- week. paroxetine 20mg. week double-blind blind extension. extension. Follow-up 8 weeks 8 weeks 8 weeks 8 weeks Primary Safety and Safety and efficacy; Safety and HAM-D. outcome efficacy; day 56 HAM-D. tolerability. Hamilton 3 April 2008 National Horizon Scanning Centre News on emerging technologies in healthcare

depression rating scale (HAM-D) total score. Secondary Clinical global CGI; MADRS. - CGI; sexual outcomes impression (CGI) functioning severity score; questionnaire Montgomery (SFQ). Asberg depression rating (MADRS). Expected Study started Study started April Study started Study started reporting December 2004. 2005. Expected January 2007. February 2008. date Expected reporting reporting date Expected reporting Expected reporting date unknown. unknown. date unknown. date unknown.

Trial code NCT00336713 NCT0041514215; MDD; NCT0053162216; MDD; (MAGENTA)14; relapse saredutant vs escitalopram; saredutant with trial; MDD; phase III. phase III. escitalopram; phase III. Sponsor Sanofi-Aventis Sanofi-Aventis Sanofi-Aventis Status Ongoing Ongoing Recruiting Location USA USA, South America, USA, South America, Europe Europe Design Randomised, double-blind, Randomised, double-blind, Randomised, double-blind, placebo-controlled. controlled. placebo-controlled. Participants n=800; adults; MDD; n=375; adults ≥ 60 years; n=615; adults 18 to 65 in trial patients who responded to MDD. Randomised to years; MDD. 12 weeks open-label. saredutant 100mg once Randomised to saredutant Randomised to saredutant daily or escitalopram. 100mg once daily with 100mg once daily or escitalopram 10mg once placebo. daily or placebo with escitalopram 10mg once daily. Follow-up 24 and 52 weeks 8, 24 weeks; 56 weeks 8 weeks Primary Time to relapse; safety and Safety and efficacy; HAM- Safety and efficacy; HAM- outcome efficacy. D. D. Secondary CGI; HAM-D; MADRS. CGI; MADRS. CGI; sexual functioning outcomes questionnaire (SFQ). Expected Study started May 2006. Study started December Study started September reporting Expected reporting date 2006. Expected reporting 2007. Expected reporting date unknown. date unknown. date unknown.

Trial code NCT0039065017; GAD; NCT0039053318; GAD; NCT0041711819; GAD; saredutant vs escitalopram; saredutant vs placebo; saredutant vs escitalopram; phase III. phase III. phase III. Sponsor Sanofi-Aventis Sanofi-Aventis Sanofi-Aventis Status Completed Ongoing Ongoing Location USA and Canada USA and Australia Canada and Europe Design Randomised, double-blind, Randomised, double-blind, Randomised, double-blind, controlled. placebo-controlled. controlled. Participants n=360; adults; GAD. n=405; adults; GAD. n=360; adults; GAD. in trial Randomised to: saredutant Randomised to: saredutant Randomised to: saredutant 100mg once daily or 100mg, 30mg once daily or 100mg or escitalopram. escitalopram. placebo. Follow-up 8 weeks 8 weeks, 56 weeks 8 weeks Primary Safety and efficacy; day 56 Safety and efficacy; HAM- Safety and efficacy; HAM- outcome Hamilton anxiety rating A. A. 4 April 2008 National Horizon Scanning Centre News on emerging technologies in healthcare

scale (HAM-A) total score. Secondary CGI CGI CGI outcomes Expected Study started October Study started October 2006. Study started December reporting 2006. Expected reporting Expected reporting date 2006. Expected reporting date date unknown. unknown. date unknown.

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

Drug Dose per day Cost per montha Amitriptyline 75 - 150 mg £13 - £26 Escitalopram 20 - 40 mg £96 - £162 Moclobemide 150 - 600 mg £60 - £180 Mirtazapine 15 - 45 mg £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. 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 National Institute for Health and Clinical Excellence. Anxiety: management of anxiety (panic disorder, with or without agoraphobia, and generalised anxiety disorder) in adults in primary, secondary and community care. Clinical guideline CG22. December 2004 (Expected review December 2008).

a Costs from British National Formulary No. 55, March 2008. 5 April 2008 National Horizon Scanning Centre News on emerging technologies in healthcare

7 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). 8 EMedicine. Depression. Available at: http://www.emedicine.com/rc/rc/i7/depression.htm (Accessed 4/3/08). 9 MIND, National Association for Mental Health. Depression and anxiety. Available at: http://www.mind.org.uk/Information/Booklets/ Understanding/Understanding+depression.htm (Accessed 4/3/08). 10 Clinical Trials. An Eight-Week Study to Evaluate the Efficacy and Safety of Saredutant in Patients With Depression. Available at: http://clinicaltrials.gov/ct2/show/NCT00256113?term=NCT00256113&rank=1 (Accessed 4/3/08). 11 Clinical Trials. An Eight-Week Study to Evaluate the Efficacy and Safety of Saredutant in Patients With Depression. Available at: http://clinicaltrials.gov/ct2/show/NCT00250614?term=NCT00250614&rank=1 (Accessed 4/3/08). 12 Clinical Trials. An Eight-Week Study to Evaluate the Efficacy and Safety of Saredutant in Patients With Depression. Available at: http://clinicaltrials.gov/ct2/show/NCT00429260?term=NCT00429260&rank=1 (Accessed 4/3/08). 13 Clinical Trials. An Eight-Week Study to Evaluate the Efficacy and Safety of Saredutant and paroxetine in combination for Patients With Depression. Available at: http://clinicaltrials.gov/ct2/show/NCT00629551 ?term=saredutant+depression&rank=5 (Accessed 15/3/08). 14Clinical Trials. Long-term Efficacy and Safety of Saredutant in Patients With Depression. Available at: http://clinicaltrials.gov/ct2/show/NCT00336713?term=NCT00336713&rank=1 (Accessed 4/3/08). 15 Clinical Trials. An Eight-Week Study to Evaluate the Efficacy and Safety of Saredutant in Elderly Patients With Depression. Available at: http://clinicaltrials.gov/ct2/show/NCT00415142?term=NCT00415142&rank=1 (Accessed 4/3/08). 16 Clinical Trials. An Eight-Week Study to Evaluate the Efficacy and Safety of Saredutant in combination with Escitalopram Patients With Depression. Available at: http://clinicaltrials.gov/ct2/show/NCT00531622? term=NCT00531622&rank=1 (Accessed 4/3/08). 17 Clinical Trials. An Eight-Week Study to Evaluate the Efficacy and Safety of Saredutant in Patients With Generalized Anxiety Disorder. Available at: http://clinicaltrials.gov/ct2/show/NCT00390650? term=NCT00390650&rank=1 (Accessed 4/3/08). 18 Clinical Trials. An Eight-Week Study to Evaluate the Efficacy and Safety of two doses of Saredutant in Patients With Generalized Anxiety Disorder. Available at: http://clinicaltrials.gov/ct2/show/NCT00390533? term=NCT00390533&rank=1 (Accessed 4/3/08). 19 Clinical Trials. An Eight-Week Study to Evaluate the Efficacy and Safety of Saredutant in Patients With Generalized Anxiety Disorder. Available at: http://clinicaltrials.gov/ct2/show/NCT00417118? term=NCT00417118&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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