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Intepirdine for Dementia with Lewy Bodies

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Intepirdine for Dementia with Lewy Bodies October Horizon Scanning Research & 2016 Intelligence Centre Intepirdine for dementia with Lewy bodies NIHR HSRIC ID: 12196 Lay summary Intepirdine is a new drug to treat patients with dementia with Lewy bodies. Lewy bodies are deposits of an abnormal protein inside brain cells. These deposits build up in areas of the brain responsible for things such as memory and muscle movement. It is not clear why the deposits develop and how exactly they damage the brain. Intepridine is taken by mouth and causes the release of chemicals in the brain that may improve cognition and function. There is currently no cure for dementia with Lewy bodies or any medication that slow progression down. 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 • Dementia with Lewy bodies. TECHNOLOGY DESCRIPTION Intepirdine (RVT-101; SB-742457; GSK 742457) is a serotonin 6 receptor antagonist which causes the release of acetylcholine and other neurotransmitters that may improve cognition and function in dementia with Lewy bodies. Intepirdine is administered orally at either 35mg or 70mg once daily1. Intepirdine does not currently have Marketing Authorisation in the EU for any indication. Intepirdine is in phase III clinical trials for mild to moderate Alzheimer’s disease in combination with donepezil. INNOVATION and/or ADVANTAGES If licensed, intepirdine will offer an additional treatment option for dementia with Lewy bodies. DEVELOPER Axovant Sciences Ltd. AVAILABILITY, LAUNCH OR MARKETING In phase II 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. It adversely affects higher cortical functions, including memory, thinking, orientation, comprehension, calculation, learning capacity, language and judgement. The symptoms of dementia with Lewy bodies usually develop gradually becoming more severe over the course of a few years. People with dementia with Lewy bodies may have specific symptoms that can help distinguish it from other types of dementia, including extreme swings between alertness, confusion and drowsiness; slow movement, stiff limbs and tremors (as seen in Parkinson's disease); hallucinations; fainting, unsteadiness and falls; sleep disturbances; loss of facial expression; dysphagia and depression3. CLINICAL NEED and BURDEN OF DISEASE Dementia with Lewy bodies is a common form of dementia estimated to affect more than 100,000 people in the UK4. Dementia with Lewy bodies accounts for 4% of all recorded Horizon Scanning Research & Intelligence Centre dementia, but there is good evidence that the condition is not always diagnosed correctly. Based on studies of brain tissue after death, scientists think dementia with Lewy bodies may account for as much as 10-15% of all dementia5. The rate of disease progression and life expectancy varies; on average, someone might live for about 6-12 years after the first symptoms5. The population likely to be eligible to receive intepirdine could not be estimated from available published sources. PATIENT PATHWAY RELEVANT GUIDANCE NICE Guidance • NICE clinical guideline in development. Dementia – assessment, management and support for people living with dementia and their carers (CG42 update). Expected August 2017. • NICE clinical guideline. Dementia: supporting people with dementia and their carers in health and social care (CG42). November 2006. • NICE guidelines. Older people: independence and mental wellbeing (NG32). December 2015. • NICE guidelines. Older people with social care needs and multiple long-term conditions (NG22). November 2015. • NICE guidelines. 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. • NICE quality standard. Dementia: independence and wellbeing (QS30). April 2013. • NICE quality standard. Dementia: support in health and social care (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. 3 Horizon Scanning Research & Intelligence Centre Other Guidance • NHS Clinical Knowledge Summary. Dementia. 20166. • Scottish Intercollegiate Guidelines Network. Management of patients with dementia (86). 20067. CURRENT TREATMENT OPTIONS There is no cure for dementia with Lewy bodies and there are currently no medications that slow progression. Acetylcholinesterase inhibitors such as donepezil, galantamine or rivastigmine (which are licensed for mild to moderate dementia in Alzheimer’s disease, but unlicensed for dementia with Lewy bodies) have been shown to improve symptoms such as hallucinations, confusion and drowsiness in some people4,8. 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: 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, care homes, physiotherapy, and speech and language therapy2,4,9. EFFICACY and SAFETY Trial The HEADWAY-DLB NCT02928445, RVT-101- NCT02910102, RVT-101- Study, NCT02669433, 2002; aged 50-86 yrs; 2003; adults aged 50-89 RVT-101-2001; aged 50- intepirdine; phase II yrs; intepirdine vs placebo; 85 yrs; intepirdine vs extension. phase II. placebo; phase IIb. Sponsor Axovant Sciences Ltd. Axovant Sciences Ltd. Axovant Sciences Ltd. Status Ongoing. Ongoing. Ongoing. Source of Trial registry1. Trial registry10. Trial registry11. information Location USA, France and Spain. USA, France and Spain. USA. Design Randomised, placebo- Extension. Randomised, placebo- controlled. controlled. Participants n=240 (planned); aged 50- n=240 (planned); aged 50- n=40 (planned); aged 50- 85 yrs; probable dementia 86 yrs; pts that have 89 yrs; a clinical diagnosis with Lewy bodies; Mini completed last on- of Alzheimer’s disease; Mental State Examination treatment visit of the MMSE score 14-26; gait (MMSE) score 14-26; HEADWAY Study. impairment; stable reliable caregiver who is background willing to report on the acetylcholinesterase subject's status. inhibitor therapy. Schedule Randomised to intepirdine Pts previously randomised Randomised to intepirdine 35mg or 70mg; or placebo; to placebo receive 35mg; or placebo; oral oral once daily. intepirdine 70mg. Pts once daily. previously randomized to intepirdine will continue in the same treatment arm. Follow-up Active treatment 24 wks, Active treatment 24 wks, Active treatment 12 wks, follow-up 24 wks. follow-up 24 wks. follow-up 12 wks. 4 Horizon Scanning Research & Intelligence Centre Primary Clinician's Interview-Based Adverse events (AEs); Quantitative gait outcome/s Impression of Change Plus change in physical measurements based on Caregiver Input (CIBIC+); examinations, vital signs, computerised gait computerised cognitive electrocardiograms assessment tools. battery. (ECGs), and clinical laboratory assessments. Secondary Clinical assessment of AEs. No quality of life AEs. outcome/s visual hallucinations; EQ- measurement included in 5D; AEs. trial outcomes. Expected Estimated primary Estimated primary Estimated primary reporting completion date October completion date March completion date date 2017. 2018. September 2017. ESTIMATED COST and IMPACT COST The cost of intepirdine is not yet known. IMPACT - SPECULATIVE Impact on Patients and Carers Reduced mortality/increased length of survival Reduced symptoms or disability Other No impact identified Impact on Health and Social Care Services Increased use of existing services Decreased use of existing services Re-organisation
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