October Horizon Scanning Research & 2016 Intelligence Centre Solanezumab for mild dementia due to Alzheimer’s disease NIHR HSRIC ID: 4777 Lay summary Solanezumab is a new drug to treat Alzheimer’s disease in people with mild symptoms. Solanezumab is delivered straight into the blood and binds to the abnormal proteins in the brain which helps to clear them, this is thought to delay the disability associated with Alzheimer’s disease. At the moment, there are no drugs that treat the underlying problem that causes Alzheimer’s disease and no known cure. This 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 or commissioning without additional information. This briefing presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health. Horizon Scanning Research & Intelligence Centre University of Birmingham [email protected] www.hsric.nihr.ac.uk @OfficialNHSC TARGET GROUP • Alzheimer’s disease (AD): mild dementia due to AD; alone or in combination with symptomatic standard of care. TECHNOLOGY DESCRIPTION Solanezumab (LY2062430, M266, MAb266) is a humanised monoclonal antibody directed against amyloid-beta (Aβ), a peptide thought to play a central role in the pathogenesis of AD. Solanezumab is thought to exert its therapeutic effect by binding to soluble Aβ and increasing its clearance from the brain. It is expected that treatments that increase the clearance of Aβ might delay the disability associated with AD. In the phase III clinical trials, solanezumab is administered by intravenous (IV) infusion 400mg once every four weeks for 80 weeks1. Solanezumab does not currently have Marketing Authorisation in the EU for any indication. INNOVATION and/or ADVANTAGES If licensed, solanezumab may provide a novel, additional treatment option for this patient group, whose therapeutic options are currently limited. DEVELOPER Eli Lilly and Company Ltd. AVAILABILITY, LAUNCH OR MARKETING In phase III clinical trials. PATIENT GROUP BACKGROUND Dementia is a chronic progressive mental disorder, which is largely irreversible and characterised by a widespread impairment of mental function2,3. It adversely affects higher cortical functions, including memory, thinking, orientation, comprehension, calculation, learning capacity, language, and judgement. AD is the most common form of dementia. It is a degenerative cerebral disease with characteristic neuropathological and neurochemical features3. AD is usually insidious in onset and develops over several years. People with AD may find it increasingly difficult to undertake everyday activities such as shopping, socialising, communication, and recognising people and places. In the later stages of the disease, physical impairments can include problems with eating (including dysphagia), incontinence, unsettled behaviour, and behaviour that challenges. AD may also be associated with loss of confidence and feelings of fear, confusion, apathy, stigma, and depression. The effects of AD are heterogeneous and vary from patient to patient3. Horizon Scanning Research & Intelligence Centre A common tool to measure cognitive functioning is the mini mental state examination (MMSE)4. The MMSE is scored out of 30. Although scores of 24 or less are strongly associated with dementia in an appropriate clinical context, scores of >24 can be seen in some people with mild dementia. A score of ≥20 suggests mild dementia, 13 – 20 suggests moderate dementia, and ≤12 indicates severe dementia. On average, the MMSE score of a person with Alzheimer's declines about two to four points each year5. CLINICAL NEED and BURDEN OF DISEASE The number of people with dementia in the UK is estimated to be 850,000, representing 1.3% of the UK population6,7. AD accounts for around 60% of all dementia cases3,8. The UK incidence of AD in people over the age of 65 years was an estimated 4.9 per 1,000 person- years in 20113. Approximately 64% of people with AD are estimated to have mild to moderate disease3. In 2014-15, there were 4,866 hospital admissions in England due to AD (ICD-10 G30), resulting in 9,364 finished consultant episodes and 318,152 bed days9. Expert opinion suggests the number of hospital admissions related to Alzheimer’s disease may be higher than this figure as many patients are admitted for a different reason but AD is a significant factora. Expert opinion also suggests that AD is associated with longer durations of hospital stay and, for many diseases, worse outcomeb. In 2014 in England and Wales, 11,298 deaths were registered in which Alzheimer’s disease was the underlying cause of death (ICD-10 G30)10. PATIENT PATHWAY RELEVANT GUIDANCE NICE Guidance • NICE technology appraisal. Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease (TA217). March 2011. • NICE clinical guideline in development. Dementia - assessment, management and support for people living with dementia and their carers (CG42 update). Expected September 2017. • NICE clinical guideline. Dementia: Supporting people with dementia and their carers in health and social care (CG42). November 2006. • NICE guideline. Older people: independence and mental wellbeing (NG32). December 2015. • NICE guideline. Older people with social care needs and multiple long-term conditions (NG22). November 2015. • NICE guideline. Dementia, disability and frailty in later life – mid-life approaches to delay or prevent onset (NG16). October 2015. • NICE quality standard. Mental wellbeing of older people in care homes (QS50). December 2013. a Expert personal opinion 3 Horizon Scanning Research & Intelligence Centre • NICE quality standard. Quality standard for supporting people to live well with dementia (QS30). April 2013. • NICE quality standard. Dementia quality standard (QS1). June 2010. • NICE advice. Management of aggression, agitation and behavioural disturbances in dementia: valproate preparations (ESUOM41). March 2015. • NICE advice. Management of aggression, agitation and behavioural disturbances in dementia: carbamazepine (ESUOM40). March 2015. • NICE advice. Low-dose antipsychotics in people with dementia (KTT7). January 2015. NHS England Policies and Guidance • NHS England. Enhanced Service Specification: facilitating timely diagnosis and support for people with dementia 2015/16. • NHS England. Dementia diagnosis and management-A brief pragmatic resource for general practitioners. February 2015. • NHS commissioning Board. Commissioning for quality and innovation (CQUIN): Improving dementia and delirium care. February 2015. • NHS England. 2013/14 NHS Standard Contract for Neurosciences: Specialised Neurology (Adult). D04/S/a. • NHS England. 2013/14 NHS Standard Contract for Complex Disability Equipment: alternative and augmentative communication/communication aids (all ages). DO1/S/b. Other Guidance • NHS Clinical Knowledge Summary. Dementia. 201611. • European Federation of Neurological Societies. EFNS guidelines for the diagnosis and management of Alzheimer’s disease. 201012. • British Association of Psychopharmacology. Clinical practice with anti-dementia drugs. 201013. • European Medicines Agency. Guideline on medicinal products for the treatment of Alzheimer’s disease and other dementias. 200814. • Scottish Intercollegiate Guidelines Network. Management of patients with dementia (86). 200615. CURRENT TREATMENT OPTIONS There is currently no disease modifying treatment for AD. Treatment aims to promote independence, maintain function, and treat symptoms; including non-cognitive (such as hallucinations, delusions, anxiety, marked agitation and associated aggressive behaviour), cognitive, behavioural, and psychological symptoms2. Non-pharmacological management options include: cognitive stimulation, social support, increasing assistance with day-to-day activities, information and education, carer support groups, community dementia teams, home nursing and personal care, community services (such as meals-on-wheels), befriending services, day centres, respite care, and care homes2,3. Pharmacological options for mild to moderate AD include acetylcholinesterase inhibitors such as donepezil, galantamine, and rivastigmine. These drugs can temporarily reduce some symptoms of the condition in some people6. 4 Horizon Scanning Research & Intelligence Centre EFFICACY and SAFETY Trial EXPEDITION, EXPEDITION 2, EXPEDITION EXT, NCT00905372, 6747, NCT00904683, 11934, NCT01127633, 11935, H8A-MC-LZAM; H8A-MC-LZAN; H8A-MC-LZAO; solanezumab vs placebo; solanezumab vs placebo; solanezumab; phase III. phase III. phase III. Sponsor Eli Lilly and Company. Eli Lilly and Company. Eli Lilly and Company. Status Published. Published. Ongoing. Source of Publication16, trial Publication16, trial registry1. Publication18, trial information registry17. registry19. Location Argentina, Brazil, Canada, EU (incl UK), USA and EU (incl UK), USA, Japan and USA. other countries. Canada and other countries. Design Randomised, placebo- Randomised, placebo- Uncontrolled, single arm. controlled. controlled. Participants n=1,012; aged ≥55 yrs; n=1,040; aged ≥55 yrs; n=975; aged ≥55 yrs; mild to moderate AD; mild to moderate AD; probable AD; completed MMSE score of 16-26; MMSE score of 16-26; participation in